graph view:
InfraNodus
×  ⁝⁝ 
Graph Language Processing Settings:

 
Specify the settings for your text-to-network conversion algorithm for this graph.
Lemmatizer: ?
Every word will be converted to its lemma (e.g. bricks > brick, taken > take) and will be shown on the graph as a node. Set to your language for more precise results. Switch off to turn off lemmatization and add your custom stop words list below.
 
Show on Graph:   Double Brackets [[]]:  Categories and Tags:   
Stop Words: ?
List the words, comma-separated (no spaces), that should not appear in the graph, in addition to your default global stopwords list.
Example: is,the,as,to,in

 
Synonym Nodes: ? unmerge all
If you'd like some words to appear as one node on the graph, in addition to your default global synonyms list, list the synonyms, one per line.
Example:
machine:machine learning
learning:machine learning

 

×  ⁝⁝ 
Dynamic Graph Settings


See the dynamic evolution of this graph: scroll or "play" the text entries to see how the text propagated through the network graph over time.

the final graph

highlight propagation edge
show visible statements only



 
Play the Graph


current speed of the player:
0 2000

one statement at a time


×  ⁝⁝ 
Export the Data


Network Graph Images:

The graph images for publishing on the web or in a journal. For embeds and URLs use the share menu.
PNG (Image)  SVG (Hi-Res)

Visible Statements (Tagged):

Export the currently filtered (visible) statements with all the meta-data tags (topics, sentiment).
CSV (Spreadsheet)   MD (e.g.Obsidian)  

Text Mining Analytics:

Summary of insights from the analytics panel. For specific in-depth exports, see the download button in the Analytics panel.
TXT Analytics Report  CSV Report  N-Grams CSV

Network Graph Data:

The raw data with all the statistics for further analysis in another software.
JSON  CSV  Gexf (Gephi)

All the Text (for backup and duplicating):

Plain text used to create this graph without any meta-data
Download Plain Text (All Statements)
× ⁝⁝ 
Share Graph Image

 
Share a non-interactive image of the graph only, no text:
Download Image Tweet
 
Share Interactive Text Graph

 

 
×  ⁝⁝ 
Save This Graph View:

 

×  ⁝⁝ 
Delete This Graph:

 

×  ⁝⁝ 
Your Project Notes
Interpret graph data, save ideas, AI content, and analytics reports. Add Analytics
Top keywords (global influence):
Top topics (local contexts):
Explore the main topics and terms outlined above or see them in the excerpts from this text below.
See the relevant data in context: click here to show the excerpts from this text that contain these topics below.
Tip: use the form below to save the most relevant keywords for this search query. Or start writing your content and see how it relates to the existing search queries and results.
Tip: here are the keyword queries that people search for but don't actually find in the search results.

symptom networks there is no such common cause. Second, symptom network relations depend on the content of mental states and as such feature intentionality. Third, the strength of network relations is highly likely to partially depend on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's (1987) notion of real patterns, and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic

   edit   deselect   + to AI

 

research strategy is necessary for progress in the study of mental disorders. Behav Brain Sci Brain disorders? PubMed C:\Users\SarahCatanese\Zotero\storage\8RDCDP6I\8RDCDP6I.pdf; http://www.ncbi.nlm.nih.gov/pubmed/29361992

   edit   deselect   + to AI

 

report 2021 Singh, Fiza; University of California, San Diego; National Institutes of Health (NIH) Enhancing Gamma Band Response in Schizophrenia to Improve Working https://clinicaltrials.gov/ct2/show/NCT03260257 Schizophrenia affects 2.4 million Americans and causes significant individual and societal costs. Cognitive deficits including poor working memory arise early in the course of illness, account for poor long-term outcomes and have been difficult to treat with available treatments. The investigators are proposing to develop a novel, computer-based brain training to improve working memory in schizophrenia patients, which, if successful could have significant personal, societal, and economic impact. A Neurofeedback Intervention to Improve Working Memory in Schizophrenia clinicaltrials.gov clinicaltrials.gov

   edit   deselect   + to AI

 

journalArticle 2016 Friston, Karl; Brown, Harriet R.; Siemerkus, Jakob; Stephan, Klaas E. The dysconnection hypothesis (2016) Schizophrenia Research 10.1016/j.schres.2016.07.014 https://www.sciencedirect.com/science/article/pii/S0920996416303310 Twenty years have passed since the dysconnection hypothesis was first proposed (Friston and Frith, 1995; Weinberger, 1993). In that time, neuroscience has witnessed tremendous advances: we now live in a world of non-invasive neuroanatomy, computational neuroimaging and the Bayesian brain. The genomics era has come and gone. Connectomics and large-scale neuroinformatics initiatives are emerging everywhere. So where is the dysconnection hypothesis now? This article considers how the notion of schizophrenia as a dysconnection syndrome has developed – and how it has been enriched by recent advances in clinical neuroscience. In particular, we examine the dysconnection hypothesis in the context of (i) theoretical neurobiology and computational

   edit   deselect   + to AI

 

psychiatry; (ii) the empirical insights afforded by neuroimaging and associated connectomics – and (iii) how bottom-up (molecular biology and genetics) and top-down (systems biology) perspectives are converging on the mechanisms and nature of dysconnections in schizophrenia. Schizophrenia Research ScienceDirect C:\Users\SarahCatanese\Zotero\storage\KXWL4Q4A\Friston et al. - 2016 - The dysconnection hypothesis (2016).pdf; C:\Users\SarahCatanese\Zotero\storage\IPDRE8RP\S0920996416303310.html Bayesian; Dysconnection; Neurogenetics; Neuromodulation; Predictive coding; Schizophrenia

   edit   deselect   + to AI

 

journalArticle 2017 Matzke, Dora; Hughes, Matthew; Badcock, Johanna C.; Michie, Patricia; Heathcote, Andrew Failures of cognitive control or attention? The case of stop-signal deficits in schizophrenia Attention, Perception, & Psychophysics 10.3758/s13414-017-1287-8 https://doi.org/10.3758/s13414-017-1287-8 We used Bayesian cognitive modelling to identify the underlying causes of apparent inhibitory deficits in the stop-signal paradigm. The analysis was applied to stop-signal data reported by Badcock et al. (Psychological Medicine 32: 87-297, 2002) and Hughes et al. (Biological Psychology 89: 220-231, 2012), where schizophrenia patients and control participants made rapid choice responses, but on some trials were signalled to stop their ongoing response. Previous research has assumed an inhibitory deficit in schizophrenia, because estimates of the mean time taken to react to the stop signal are longer in patients than controls. We showed that these longer estimates are partly due to

   edit   deselect   + to AI

 

failing to react to the stop signal (“trigger failures”) and partly due to a slower initiation of inhibition, implicating a failure of attention rather than a deficit in the inhibitory process itself. Correlations between the probability of trigger failures and event-related potentials reported by Hughes et al. are interpreted as supporting the attentional account of inhibitory deficits. Our results, and those of Matzke et al. (2016), who report that controls also display a substantial although lower trigger-failure rate, indicate that attentional factors need to be taken into account when interpreting results from the stop-signal paradigm. Atten Percept Psychophys Failures of cognitive control or attention? Springer Link C:\Users\SarahCatanese\Zotero\storage\8KWME5NZ\Matzke et al_2017_Failures of cognitive control or attention.pdf

   edit   deselect   + to AI

 

journalArticle 2018 Sterzer, Philipp; Adams, Rick A.; Fletcher, Paul; Frith, Chris; Lawrie, Stephen M.; Muckli, Lars; Petrovic, Predrag; Uhlhaas, Peter; Voss, Martin; Corlett, Philip R. The Predictive Coding Account of Psychosis Biological Psychiatry 10.1016/j.biopsych.2018.05.015 https://www.biologicalpsychiatryjournal.com/article/S0006-3223(18)31532-4/abstract <h2>Abstract</h2><p>Fueled by developments in computational neuroscience, there has been increasing interest in the underlying neurocomputational mechanisms of psychosis. One successful approach involves predictive coding and Bayesian inference. Here, inferences regarding the current state of the world are made by combining prior beliefs with incoming sensory signals. Mismatches between prior beliefs and incoming signals constitute prediction errors that drive new learning. Psychosis has been suggested to result from a decreased precision in the encoding of prior beliefs relative to the sensory data, thereby garnering

   edit   deselect   + to AI

 

maladaptive inferences. Here, we review the current evidence for aberrant predictive coding and discuss challenges for this canonical predictive coding account of psychosis. For example, hallucinations and delusions may relate to distinct alterations in predictive coding, despite their common co-occurrence. More broadly, some studies implicate weakened prior beliefs in psychosis, and others find stronger priors. These challenges might be answered with a more nuanced view of predictive coding. Different priors may be specified for different sensory modalities and their integration, and deficits in each modality need not be uniform. Furthermore, hierarchical organization may be critical. Altered processes at lower levels of a hierarchy need not be linearly related to processes at higher levels (and vice versa). Finally, canonical theories do not highlight active inference—the process through which the effects of our actions on our sensations are anticipated and minimized. It is possible

   edit   deselect   + to AI

 

that conflicting findings might be reconciled by considering these complexities, portending a framework for psychosis more equipped to deal with its many manifestations.</p> Biological Psychiatry www.biologicalpsychiatryjournal.com C:\Users\SarahCatanese\Zotero\storage\JBQ3QJA5\Sterzer et al. - 2018 - The Predictive Coding Account of Psychosis.pdf; http://www.ncbi.nlm.nih.gov/pubmed/30007575

   edit   deselect   + to AI

 

webpage CPSYMAP CPSYMAP https://ncnp-cpsy-rmap.web.app The Computational Psychiatry Research Map (CPSYMAP) is a tool for visualizing research papers from computational psychiatry as a two-dimensional "map". Using this map, explore the distribution of papers along neuroscientific, psychiatric and computational dimensions. C:\Users\SarahCatanese\Zotero\storage\TYK2JJCH\search.html

   edit   deselect   + to AI

 

journalArticle 2020 Tost, Meritxell; Monreal, José Antonio; Armario, Antonio; Barbero, Juan David; Cobo, Jesús; García-Rizo, Clemente; Bioque, Miquel; Usall, Judith; Huerta-Ramos, Elena; Soria, Virginia; PNECAT Group; Labad, Javier Targeting Hormones for Improving Cognition in Major Mood Disorders and Schizophrenia: Thyroid Hormones and Prolactin Clinical Drug Investigation 10.1007/s40261-019-00854-w Cognitive deficits are a core feature of serious mental illnesses such as major depression, bipolar disorder and schizophrenia and are a common cause of functional disability. However, the efficacy of pharmacological interventions for improving the cognitive deficits in these disorders is limited. As pro-cognitive pharmacological treatments are lacking, we aimed to review whether thyroid hormones or drugs that target prolactin may become potential candidates for 'repurposing' trials aiming to improve cognition. We conducted a narrative review focused on thyroid hormones and prolactin as

   edit   deselect   + to AI

 

potential targets for improving cognition in major mood disorders or schizophrenia. The role of thyroid hormones and prolactin on cognitive processes in non-psychiatric populations was also reviewed. Although clinical trials regarding these hormones are lacking, particularly in patients with schizophrenia, bipolar disorder or major depression, there is evidence from observational studies for the contribution of these hormones to cognitive processes. Patients with bipolar disorder and subclinical hypothyroidism show poorer cognitive function than euthyroid patients. In patients with early psychosis, lower free thyroxine concentrations have been associated with poorer attention whereas increased prolactin levels have been associated with poorer speed of processing. Only two small clinical trials tested the potential pro-cognitive effects of thyroid hormones, with positive findings for triiodothyronine (T3) treatment in patients receiving lithium or electroconvulsive therapy. In sum,

   edit   deselect   + to AI

 

thyroid hormones and prolactin might contribute to the cognitive performance of patients with major mood disorders and psychotic disorders. Thyroid hormones and prolactin-lowering drugs (e.g. cabergoline, aripiprazole) are candidate drugs to be tested in repurposing clinical trials aiming to improve the cognitive abilities of patients with major mood disorder and schizophrenia. Clin Drug Investig Targeting Hormones for Improving Cognition in Major Mood Disorders and Schizophrenia PubMed http://www.ncbi.nlm.nih.gov/pubmed/31612424 Schizophrenia; Humans; Bipolar Disorder; Cognition Disorders; Depressive Disorder, Major; Hypothyroidism; Mood Disorders; Prolactin; Psychotic Disorders; Thyroid Hormones; Triiodothyronine

   edit   deselect   + to AI

 

journalArticle 2018 MacKay, Mary-Anne B.; Paylor, John W.; Wong, James T. F.; Winship, Ian R.; Baker, Glen B.; Dursun, Serdar M. Multidimensional Connectomics and Treatment-Resistant Schizophrenia: Linking Phenotypic Circuits to Targeted Therapeutics Frontiers in Psychiatry 10.3389/fpsyt.2018.00537 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218602/ Schizophrenia is a very complex syndrome that involves widespread brain multi-dysconnectivity. Neural circuits within specific brain regions and their links to corresponding regions are abnormal in the illness. Theoretical models of dysconnectivity and the investigation of connectomics and brain network organization have been examined in schizophrenia since the early nineteenth century. In more recent years, advancements have been achieved with the development of neuroimaging tools that have provided further clues to the structural and functional organization of the brain and global neural networks in the illness. Neural circuitry that

   edit   deselect   + to AI

 

extends across prefrontal, temporal and parietal areas of the cortex as well as limbic and other subcortical brain regions is disrupted in schizophrenia. As a result, many patients have a poor response to antipsychotic treatment and treatment failure is common. Treatment resistance that is specific to positive, negative, and cognitive domains of the illness may be related to distinct circuit phenotypes unique to treatment-refractory disease. Currently, there are no customized neural circuit-specific and targeted therapies that address this neural dysconnectivity. Investigation of targeted therapeutics that addresses particular areas of substantial regional dysconnectivity is an intriguing approach to precision medicine in schizophrenia. This review examines current findings of system and circuit-level brain dysconnectivity in treatment-resistant schizophrenia based on neuroimaging studies. Within a connectome context, on-off circuit connectivity synonymous with excitatory and

   edit   deselect   + to AI

 

inhibitory neuronal pathways is discussed. Mechanistic cellular, neurochemical and molecular studies are included with specific emphasis given to cell pathology and synaptic communication in glutamatergic and GABAergic systems. In this review we attempt to deconstruct how augmenting treatments may be applied within a circuit context to improve circuit integration and treatment response. Clinical studies that have used a variety of glutamate receptor and GABA interneuron modulators, nitric oxide-based therapies and a variety of other strategies as augmenting treatments with antipsychotic drugs are included. This review supports the idea that the methodical mapping of system-level networks to both on (excitatory) and off (inhibitory) cellular circuits specific to treatment-resistant disease may be a logical and productive approach in directing future research toward the advancement of targeted pharmacotherapeutics in schizophrenia. Front Psychiatry Multidimensional Connectomics and

   edit   deselect   + to AI

 

Treatment-Resistant Schizophrenia PubMed Central C:\Users\SarahCatanese\Zotero\storage\JBUUJAUE\MacKay et al_2018_Multidimensional Connectomics and Treatment-Resistant Schizophrenia.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218602/

   edit   deselect   + to AI

 

journalArticle 2019 Corlett, Philip R.; Horga, Guillermo; Fletcher, Paul C.; Alderson-Day, Ben; Schmack, Katharina; Powers, Albert R. Hallucinations and Strong Priors Trends in Cognitive Sciences 10.1016/j.tics.2018.12.001 https://www.sciencedirect.com/science/article/pii/S1364661318302821 Hallucinations, perceptions in the absence of objectively identifiable stimuli, illustrate the constructive nature of perception. Here, we highlight the role of prior beliefs as a critical elicitor of hallucinations. Recent empirical work from independent laboratories shows strong, overly precise priors can engender hallucinations in healthy subjects and that individuals who hallucinate in the real world are more susceptible to these laboratory phenomena. We consider these observations in light of work demonstrating apparently weak, or imprecise, priors in psychosis. Appreciating the interactions within and between hierarchies of inference can reconcile this apparent disconnect. Data from neural

   edit   deselect   + to AI

 

networks, human behavior, and neuroimaging support this contention. This work underlines the continuum from normal to aberrant perception, encouraging a more empathic approach to clinical hallucinations. Trends in Cognitive Sciences ScienceDirect C:\Users\SarahCatanese\Zotero\storage\JDRVX9XJ\Corlett et al. - 2019 - Hallucinations and Strong Priors.pdf; C:\Users\SarahCatanese\Zotero\storage\R2CL4F9K\S1364661318302821.html psychosis; auditory verbal hallucinations; hallucinations; predictive coding; prior beliefs

   edit   deselect   + to AI

 

journalArticle 2019 Corlett, Philip R.; Horga, Guillermo; Fletcher, Paul C.; Alderson-Day, Ben; Schmack, Katharina; Powers, Albert R. Hallucinations and Strong Priors Trends in Cognitive Sciences 10.1016/j.tics.2018.12.001 https://www.sciencedirect.com/science/article/pii/S1364661318302821 Hallucinations, perceptions in the absence of objectively identifiable stimuli, illustrate the constructive nature of perception. Here, we highlight the role of prior beliefs as a critical elicitor of hallucinations. Recent empirical work from independent laboratories shows strong, overly precise priors can engender hallucinations in healthy subjects and that individuals who hallucinate in the real world are more susceptible to these laboratory phenomena. We consider these observations in light of work demonstrating apparently weak, or imprecise, priors in psychosis. Appreciating the interactions within and between hierarchies of inference can reconcile this apparent disconnect. Data from neural

   edit   deselect   + to AI

 

networks, human behavior, and neuroimaging support this contention. This work underlines the continuum from normal to aberrant perception, encouraging a more empathic approach to clinical hallucinations. Trends in Cognitive Sciences ScienceDirect C:\Users\SarahCatanese\Zotero\storage\7SYE438E\Corlett et al. - 2019 - Hallucinations and Strong Priors.pdf; C:\Users\SarahCatanese\Zotero\storage\795BZWBI\S1364661318302821.html psychosis; auditory verbal hallucinations; hallucinations; predictive coding; prior beliefs

   edit   deselect   + to AI

 

journalArticle 2020 Zhou, Mengshi; Zheng, Chunlei; Xu, Rong Combining phenome-driven drug-target interaction prediction with patients' electronic health records-based clinical corroboration toward drug discovery Bioinformatics (Oxford, England) 10.1093/bioinformatics/btaa451 MOTIVATION: Predicting drug-target interactions (DTIs) using human phenotypic data have the potential in eliminating the translational gap between animal experiments and clinical outcomes in humans. One challenge in human phenome-driven DTI predictions is integrating and modeling diverse drug and disease phenotypic relationships. Leveraging large amounts of clinical observed phenotypes of drugs and diseases and electronic health records (EHRs) of 72 million patients, we developed a novel integrated computational drug discovery approach by seamlessly combining DTI prediction and clinical corroboration. RESULTS: We developed a network-based DTI prediction system (TargetPredict) by modeling 855 904 phenotypic and

   edit   deselect   + to AI

 

genetic relationships among 1430 drugs, 4251 side effects, 1059 diseases and 17 860 genes. We systematically evaluated TargetPredict in de novo cross-validation and compared it to a state-of-the-art phenome-driven DTI prediction approach. We applied TargetPredict in identifying novel repositioned candidate drugs for Alzheimer's disease (AD), a disease affecting over 5.8 million people in the United States. We evaluated the clinical efficiency of top repositioned drug candidates using EHRs of over 72 million patients. The area under the receiver operating characteristic (ROC) curve was 0.97 in the de novo cross-validation when evaluated using 910 drugs. TargetPredict outperformed a state-of-the-art phenome-driven DTI prediction system as measured by precision-recall curves [measured by average precision (MAP): 0.28 versus 0.23, P-value < 0.0001]. The EHR-based case-control studies identified that the prescriptions top-ranked repositioned drugs are significantly associated with lower

   edit   deselect   + to AI

 

odds of AD diagnosis. For example, we showed that the prescription of liraglutide, a type 2 diabetes drug, is significantly associated with decreased risk of AD diagnosis [adjusted odds ratios (AORs): 0.76; 95% confidence intervals (CI) (0.70, 0.82), P-value < 0.0001]. In summary, our integrated approach that seamlessly combines computational DTI prediction and large-scale patients' EHRs-based clinical corroboration has high potential in rapidly identifying novel drug targets and drug candidates for complex diseases. AVAILABILITY AND IMPLEMENTATION: nlp.case.edu/public/data/TargetPredict. Bioinformatics PubMed ; C:\Users\SarahCatanese\Zotero\storage\2RXHJT3I\Zhou et al. - 2020 - Combining phenome-driven drug-target interaction p.pdf http://www.ncbi.nlm.nih.gov/pubmed/32657406 Humans; Diabetes Mellitus, Type 2; Drug Development; Drug Discovery; Electronic Health Records; Pharmaceutical Preparations

   edit   deselect   + to AI

 

journalArticle 2015 Xu, Rong; Wang, QuanQiu PhenoPredict: A disease phenome-wide drug repositioning approach towards schizophrenia drug discovery Journal of Biomedical Informatics 10.1016/j.jbi.2015.06.027 Schizophrenia (SCZ) is a common complex disorder with poorly understood mechanisms and no effective drug treatments. Despite the high prevalence and vast unmet medical need represented by the disease, many drug companies have moved away from the development of drugs for SCZ. Therefore, alternative strategies are needed for the discovery of truly innovative drug treatments for SCZ. Here, we present a disease phenome-driven computational drug repositioning approach for SCZ. We developed a novel drug repositioning system, PhenoPredict, by inferring drug treatments for SCZ from diseases that are phenotypically related to SCZ. The key to PhenoPredict is the availability of a comprehensive drug treatment knowledge base that we recently constructed. PhenoPredict retrieved all 18

   edit   deselect   + to AI

 

FDA-approved SCZ drugs and ranked them highly (recall=1.0, and average ranking of 8.49%). When compared to PREDICT, one of the most comprehensive drug repositioning systems currently available, in novel predictions, PhenoPredict represented clear improvements over PREDICT in Precision-Recall (PR) curves, with a significant 98.8% improvement in the area under curve (AUC) of the PR curves. In addition, we discovered many drug candidates with mechanisms of action fundamentally different from traditional antipsychotics, some of which had published literature evidence indicating their treatment benefits in SCZ patients. In summary, although the fundamental pathophysiological mechanisms of SCZ remain unknown, integrated systems approaches to studying phenotypic connections among diseases may facilitate the discovery of innovative SCZ drugs. J Biomed Inform PhenoPredict PubMed ; C:\Users\SarahCatanese\Zotero\storage\56VMVRS4\Xu_Wang_2015_PhenoPredict.pdf

   edit   deselect   + to AI

 

http://www.ncbi.nlm.nih.gov/pubmed/26151312 Schizophrenia; Computational Biology; Algorithms; Drug Discovery; Antipsychotic Agents; Area Under Curve; Databases, Factual; Disease phenotype; Drug Delivery Systems; Drug discovery; Drug repositioning; Drug Repositioning; Knowledge Bases; Phenotype; Reproducibility of Results; Software; Systems biology; United States; United States Food and Drug Administration

   edit   deselect   + to AI

 

journalArticle 2014 Gururajan, Anand; Buuse, Maarten van den Is the mTOR-signalling cascade disrupted in Schizophrenia? Journal of Neurochemistry https://doi.org/10.1111/jnc.12622 https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.12622 The mammalian target of rapamycin (mTOR) signalling cascade is involved in the intracellular regulation of protein synthesis, specifically for proteins involved in controlling neuronal morphology and facilitating synaptic plasticity. Research has revealed that the activity of the mTOR cascade is influenced by several extracellular and environmental factors that have been implicated in schizophrenia. Therefore, there is reason to believe that one of the downstream consequences of dysfunction or hypofunction of these factors in schizophrenia is disrupted mTOR signalling and hence impaired protein synthesis. This results in abnormal neurodevelopment and deficient synaptic plasticity, outcomes which could underlie some of the positive, negative and

   edit   deselect   + to AI

 

cognitive symptoms of schizophrenia. This review will discuss the functional roles of the mTOR cascade and present evidence in support of a novel mTOR-based hypothesis of the neuropathology of schizophrenia. During neurodevelopment, genetic and epigenetic factors can disrupt mTOR signalling which affects synthesis of proteins essential for correct neuronal growth and network connectivity. This renders the CNS particularly vulnerable to the effects of secondary factors during adolescence which increases the risk of developing schizophrenia in adulthood. This review discusses the functional roles of the mTOR cascade and presents evidence in support of a novel mTOR-based hypothesis of the neuropathology of schizophrenia. Testing this hypothesis will advance our understanding of the aetiology of this illness and reveal novel therapeutic targets. Wiley Online Library schizophrenia; BDNF; glutamate; mammalian target of rapamycin; Reelin

   edit   deselect   + to AI

 

journalArticle 2020 Okano, Kana; Bauer, Clemens C. C.; Ghosh, Satrajit S.; Lee, Yoon Ji; Melero, Helena; de Los Angeles, Carlo; Nestor, Paul G.; Del Re, Elisabetta C.; Northoff, Georg; Whitfield-Gabrieli, Susan; Niznikiewicz, Margaret A. Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence Psychiatry Research 10.1016/j.psychres.2020.112862 Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to teach 10 SZ patients with pharmacology-resistant AH to modulate their brain activity in the superior temporal gyrus

   edit   deselect   + to AI

 

(STG), a key area in the neurophysiology of AH. A functional task was designed in order to provide patients with a specific strategy to help them modify their brain activity in the desired direction. Specifically, they received neurofeedback from their own STG and were trained to upregulate it while listening to their own voice recording and downregulate it while ignoring a stranger's voice recording. This guided performance neurofeedback training resulted in a) a significant reduction in STG activation while ignoring a stranger's voice, and b) reductions in AH scores after the neurofeedback session. A single, 21-minute session of rt-fMRI NFB was enough to produce these effects, suggesting that this approach may be an efficient and clinically viable alternative for the treatment of pharmacology-resistant AH. Psychiatry Res Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction PubMed http://www.ncbi.nlm.nih.gov/pubmed/32113035

   edit   deselect   + to AI

 

journalArticle 2012 McCarthy-Jones, Simon Taking Back the Brain: Could Neurofeedback Training Be Effective for Relieving Distressing Auditory Verbal Hallucinations in Patients With Schizophrenia? Schizophrenia Bulletin 10.1093/schbul/sbs006 https://academic.oup.com/schizophreniabulletin/article/38/4/678/1869206 Abstract. Progress in identifying the neural correlates of auditory verbal hallucinations (AVHs) experienced by patients with schizophrenia has not fulfilled i Schizophr Bull Taking Back the Brain academic.oup.com C:\Users\SarahCatanese\Zotero\storage\2DGXP8BY\McCarthy-Jones - 2012 - Taking Back the Brain Could Neurofeedback Trainin.pdf; C:\Users\SarahCatanese\Zotero\storage\K2Q5NC96\1869206.html

   edit   deselect   + to AI

 

webpage Normalizing the Abnormal: Do Antipsychotic Drugs Push the Cortex Into an Unsustainable Metabolic Envelope? | Schizophrenia Bulletin | Oxford Academic https://academic.oup.com/schizophreniabulletin/article/46/3/484/5637929 C:\Users\SarahCatanese\Zotero\storage\WP9YU3L3\5637929.html

   edit   deselect   + to AI

 

webpage Quantitative EEG and normative databases Anatomical Concepts https://www.biofeedback-tech.com/articles/2017/9/19/quantitative-eeg-and-databases-meg5l Electroencephalography (EEG) reflecting the ebb and flow of electrical energy from the brain has been in and out of fashion over the years.&nbsp; It's complexity has meant that increasing interest has usually coincided with advances in hardware and software for processing it.&nbsp; So called C:\Users\SarahCatanese\Zotero\storage\MGXE7Z8U\quantitative-eeg-and-databases-meg5l.html

   edit   deselect   + to AI

 

webpage Integrative Psychiatry Institute - Psychiatry Training Online CME Integrative Psychiatry Institute https://psychiatryinstitute.com/ Learn a new, integrative approach today. Receive Continued Medical Education (CME) with our online eLearning platform for Integrative Psychiatry Training. C:\Users\SarahCatanese\Zotero\storage\AYE8D5GE\psychiatryinstitute.com.html

   edit   deselect   + to AI

 

journalArticle Thatcher, Robert W NINETEEN CHANNEL QUANTITATIVE EEG AND EEG BIOFEEDBACK Zotero C:\Users\SarahCatanese\Zotero\storage\ZY9IMCS5\Thatcher - NINETEEN CHANNEL QUANTITATIVE EEG AND EEG BIOFEEDB.pdf

   edit   deselect   + to AI

 

book 2009 Introduction to quantitative EEG and neurofeedback: advanced theory and applications 978-0-12-374534-7 Introduction to quantitative EEG and neurofeedback Academic Press/Elsevier Library of Congress ISBN RC489.B53 I55 2009 C:\Users\SarahCatanese\Zotero\storage\GIJN68NN\Budzynski - 2009 - Introduction to quantitative EEG and neurofeedback.pdf Biofeedback training; Neurofeedback; Electroencephalography

   edit   deselect   + to AI

 

webpage tDCS Montage Guide tDCS.com https://www.tdcs.com/montage-guide Every up-to-date tDCS electrode montage out there, with electrode placement instruction using the 10/20 system--along with notes for each montage as well as their respective sources and publications. C:\Users\SarahCatanese\Zotero\storage\2386ZKRP\montage-guide.html

   edit   deselect   + to AI

 

journalArticle 2017 Zhang, Ye; Song, Weiqun; Du, Jubao; Huo, Su; Shan, Guixiang; Li, Ran Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of Consciousness: Combined Behavioral and Event-Related Potential Evidence Frontiers in Neurology 10.3389/fneur.2017.00620 https://www.frontiersin.org/articles/10.3389/fneur.2017.00620/full Background: The electrophysiological evidence supporting the therapeutic efficacy of multiple transcranial direct current stimulation (tDCS) sessions on consciousness improvement in patients with prolonged disorders of consciousness (DOCs) has not been firmly established. Objectives: To assess the effects of repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS-R) score and event-related potential (ERP). Method: Using a sham-controlled randomized double-blind design, twenty-six patients were randomly assigned to either a real (five vegetative state (VS) and eight minimally conscious state (MCS) patients) or

   edit   deselect   + to AI

 

sham (six VS and seven MCS patients) stimulation group. The patients in the real stimulation group underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 10 consecutive working days. The CRS-R score and P300 amplitude and latency in a hierarchical cognitive assessment were recorded to evaluate the consciousness level before tDCS and immediately after the 20 sessions. Results: The intra-group CRS-R analysis revealed a clinically significant improvement in the MCS patients in the real stimulation group. The inter-group CRS-R analysis showed a significant difference in CRS-R between VS and MCS patients at baseline in both the real and sham stimulation groups. The intra-group ERP analysis revealed a significant increase in P300 amplitude after tDCS in the MCS patients in the real stimulation group, but no significant differences in P300 latency. For the inter-group ERP analysis, we observed significant differences regarding the presence of P300 at

   edit   deselect   + to AI

 

baseline between the VS and MCS patients in both groups. Conclusion: The repeated anodal tDCS of the left DLPFC could produce clinically significant improvements in MCS patients. The observed tDCS-related consciousness improvements might be related to improvements in attention resource allocation (reflected by the P300 amplitude). The findings support the use of tDCS in clinical practice and ERP might serve as an efficient electrophysiological assessment tool in patients with DOCs. Front. Neurol. Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of Consciousness Frontiers C:\Users\SarahCatanese\Zotero\storage\NBSSU9TY\Zhang et al. - 2017 - Transcranial Direct Current Stimulation in Patient.pdf P300; Coma Recovery Scale-Revised; disorders of consciousness; Event-related potentials; transcranial direct current stimulation

   edit   deselect   + to AI

 

journalArticle 2018 Buckley, Peter F.; Miller, Brian J. Rheumatoid Arthritis Drugs for Schizophrenia? Psychiatric Annals 10.3928/00485713-20180405-01 https://www.healio.com/psychiatry/journals/psycann/2018-5-48-5/{4a1c3326-1508-4ca0-9577-146258e785bb}/rheumatoid-arthritis-drugs-for-schizophrenia Psychiatric Annals | Any relationship between treatment of rheumatoid arthritis and the current treatment of schizophrenia seems, at first glance, far-fetched. And yet, in a relatively short period of intensive research work, the field of schizophrenia research has come to appreciate that there are fundamental immunological associations with schizophrenia. Several groups have conducted studies of antirheumatic Psychiatr Ann www.healio.com C:\Users\SarahCatanese\Zotero\storage\CYHN5S5J\rheumatoid-arthritis-drugs-for-schizophrenia.html

   edit   deselect   + to AI

 

journalArticle 2019 Kantrowitz, Joshua T.; Sehatpour, Pejman; Avissar, Michael; Horga, Guillermo; Gwak, Anna; Hoptman, Mathew J.; Beggel, Odeta; Girgis, Ragy R.; Vail, Blair; Silipo, Gail; Carlson, Marlene; Javitt, Daniel C. Significant improvement in treatment resistant auditory verbal hallucinations after 5 days of double-blind, randomized, sham controlled, fronto-temporal, transcranial direct current stimulation (tDCS): A replication/extension study Brain Stimulation 10.1016/j.brs.2019.03.003 http://www.sciencedirect.com/science/article/pii/S1935861X19300828 Background Transcranial direct current stimulation (tDCS) is a potentially novel treatment for antipsychotic-resistant auditory verbal hallucinations (AVH) in schizophrenia. Nevertheless, results have been mixed across studies. Methods 89 schizophrenia/schizoaffective subjects (active: 47; Sham: 42) were randomized to five days of twice-daily 20-min active tDCS vs. sham treatments across two recruitment sites. AVH severity was

   edit   deselect   + to AI

 

assessed using the Auditory Hallucination Rating Scale (AHRS) total score. To assess target engagement, MRI was obtained in a sub sample. Results We observed a statistically significant, moderate effect-size change in AHRS total score across one-week and one-month favoring active treatment following covariation for baseline symptoms and antipsychotic dose (p = 0.036; d = 0.48). Greatest change was observed on the AHRS loudness item (p = 0.003; d = 0.69). In exploratory analyses, greatest effects on AHRS were observed in patients with lower cognitive symptoms (d = 0.61). In target engagement analysis, suprathreshold mean field-strength (>0.2 V/m) was seen within language-sensitive regions. However, off-target field-strength, which correlated significantly with less robust clinical response, was observed in anterior regions. Conclusions This is the largest study of tDCS for persistent AVH conducted to date. We replicate previous reports of significant therapeutic benefit, but only if

   edit   deselect   + to AI

 

medication dosage is considered, with patients receiving lowest medication dosage showing greatest effect. Response was also greatest in patients with lowest levels of cognitive symptoms. Overall, these findings support continued development of tDCS for persistent AVH, but also suggest that response may be influenced by specific patient and treatment characteristics. ClinicalTrials.gov NCT01898299. Brain Stimulation Significant improvement in treatment resistant auditory verbal hallucinations after 5 days of double-blind, randomized, sham controlled, fronto-temporal, transcranial direct current stimulation (tDCS) ScienceDirect C:\Users\SarahCatanese\Zotero\storage\RSGUH95B\S1935861X19300828.html Schizophrenia; Auditory hallucinations; Clinical trial; Target engagement; tDCS

   edit   deselect   + to AI

 

blogPost 2019 ArticlesPsychology·January 9, FeaturedNeuroscienceOpen Neuroscience; 2019 Statins May Help Treat Serious Mental Illness Neuroscience News https://neurosciencenews.com/statins-mental-health-10473/ A new study reveals statins, biguanides and other drugs that help treat physical conditions may have significant benefits for the treatment of bipolar disorder and schizophrenia. C:\Users\SarahCatanese\Zotero\storage\T3CBIKHL\statins-mental-health-10473.html

   edit   deselect   + to AI

 

webpage 10-20-System-Electrode-Distances.jpg (592×618) https://www.diytdcs.com/media/10-20-System-Electrode-Distances.jpg C:\Users\SarahCatanese\Zotero\storage\IMYGM9K6\10-20-System-Electrode-Distances.html

   edit   deselect   + to AI

 

journalArticle 2009 Fisher, Melissa; Holland, Christine; Merzenich, Michael M.; Vinogradov, Sophia Using Neuroplasticity-Based Auditory Training to Improve Verbal Memory in Schizophrenia American Journal of Psychiatry 10.1176/appi.ajp.2009.08050757 http://psychiatryonline.org/doi/abs/10.1176/appi.ajp.2009.08050757 AJP DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\MMDIYRS9\Fisher et al. - 2009 - Using Neuroplasticity-Based Auditory Training to I.pdf

   edit   deselect   + to AI

 

journalArticle 2020 Maric, Vojislav; Ramanathan, Dhakshin; Mishra, Jyoti Respiratory regulation & interactions with neuro-cognitive circuitry Neuroscience & Biobehavioral Reviews 10.1016/j.neubiorev.2020.02.001 https://linkinghub.elsevier.com/retrieve/pii/S0149763419301599 Neuroscience & Biobehavioral Reviews DOI.org (Crossref)

   edit   deselect   + to AI

 

journalArticle 2011 DaSilva, Alexandre F.; Volz, Magdalena Sarah; Bikson, Marom; Fregni, Felipe Electrode Positioning and Montage in Transcranial Direct Current Stimulation Journal of Visualized Experiments 10.3791/2744 http://www.jove.com/index/Details.stp?ID=2744 Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability2. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation6. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders – especially when applied over several consecutive sessions4. One area that has been

   edit   deselect   + to AI

 

attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks3,5. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex7. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation. JoVE DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\VETIEUUQ\DaSilva et al. - 2011 - Electrode Positioning and Montage in Transcranial .pdf

   edit   deselect   + to AI

 

webpage Drug ‘Ecstasy’ May Help Individuals with Schizophrenia, Autism https://psychcentral.com/news/2010/12/17/drug-ecstasy-may-help-individuals-with-schizophrenia-autism#1 C:\Users\SarahCatanese\Zotero\storage\45SIZG52\drug-ecstasy-may-help-individuals-with-schizophrenia-autism.html

   edit   deselect   + to AI

 

webpage Nitric Oxide and Symptom Reduction in Schizophrenia | Neurology | JAMA Psychiatry | JAMA Network https://jamanetwork.com/journals/jamapsychiatry/article-abstract/1686036 C:\Users\SarahCatanese\Zotero\storage\4TMUEA2Q\1686036.html

   edit   deselect   + to AI

 

webpage Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review - PubMed https://pubmed.ncbi.nlm.nih.gov/28718181/ C:\Users\SarahCatanese\Zotero\storage\2X87RVQ4\28718181.html

   edit   deselect   + to AI

 

journalArticle 2018 Li, Xian-Bin; Zheng, Wei; Ning, Yu-Ping; Cai, Dong-Bin; Yang, Xin-Hu; Ungvari, Gabor S.; Ng, Chee H.; Wang, Chuan-Yue; Xiang, Yu-Tao Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review Pharmacopsychiatry Pharmacopsychiatry

   edit   deselect   + to AI

 

journalArticle 2019 Dellazizzo, Laura; Potvin, Stéphane; Bahig, Sami; Dumais, Alexandre Comprehensive review on virtual reality for the treatment of violence: implications for youth with schizophrenia npj Schizophrenia 10.1038/s41537-019-0079-7 https://www.nature.com/articles/s41537-019-0079-7 Youth violence is a complex and multifactorial issue that has severe health and social consequences. While treatment options exist to treat/reduce violence in at-risk populations such as schizophrenia, there remains limitations in the efficacy of current interventions. Virtual reality (VR) appears to be a unique possibility to expose offenders and to train coping skills in virtual situations that are capable of eliciting aggression‐relevant behavior without threatening others. The focus of this paper is to provide a comprehensive review of studies using VR to manage violence across several at-risk populations, with a particular emphasis on youth with schizophrenia. Despite the encouraging

   edit   deselect   + to AI

 

success of VR applications for the treatment of different mental health problems, no studies have explored the usability of VR to specifically treat violence in patients with schizophrenia. A limited number of studies have focused on violence risk factors in other mental health problems (i.e., emotion regulation in individual suffering from post-traumatic disorders) that may be targeted in treatments to reduce the risk of violence. The preliminary studies using VR as a therapeutic element have shown reductions in anger, improvements in conflict-resolution skills as well as in empathy levels, and decreases in aggression. Possible applications of these interventions in youth with schizophrenia will be discussed. Comprehensive review on virtual reality for the treatment of violence www.nature.com C:\Users\SarahCatanese\Zotero\storage\NUA3MHUZ\Dellazizzo et al. - 2019 - Comprehensive review on virtual reality for the tr.pdf

   edit   deselect   + to AI

 

journalArticle 2019 Kim, Sung-Wan; Kang, Hee-Ju; Jhon, Min; Kim, Ju-Wan; Lee, Ju-Yeon; Walker, Adam J.; Agustini, Bruno; Kim, Jae-Min; Berk, Michael Statins and Inflammation: New Therapeutic Opportunities in Psychiatry Frontiers in Psychiatry 10.3389/fpsyt.2019.00103 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413672/ Statins, which are widely used to treat hypercholesterolemia, have anti-inflammatory and anti-oxidant effects. These are thought to be responsible for the potential effects of statins on various psychiatric disorders. In this study, we comprehensively review the literature to investigate the effects of statins on various psychiatric disorders including depression, schizophrenia, and dementia. In addition, we review adverse effects and drug interactions of statins to give clinically useful information guiding statin use in the psychiatric field. Statins seem useful in reducing depression, particularly in patients with physical disorders such as cardiovascular disease.

   edit   deselect   + to AI

 

In patients with schizophrenia, negative symptoms may be reduced by adjuvant statin therapy. Studies on cohorts at risk for dementia have generally shown protective effects of statins, while those on treatment for dementia show inconsistent results. In conclusion, statins used in combination with conventional psychotropic medications may be effective for various psychiatric disorders including depression, schizophrenia, and dementia. Further study is required to determine optimal doses and duration of statin use for the treatment of psychiatric disorders. Front Psychiatry Statins and Inflammation PubMed Central C:\Users\SarahCatanese\Zotero\storage\M9LY2USU\Kim et al. - 2019 - Statins and Inflammation New Therapeutic Opportun.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413672/

   edit   deselect   + to AI

 

blogPost 2019 ArticlesPsychology·January 9, FeaturedNeuroscienceOpen Neuroscience; 2019 Statins May Help Treat Serious Mental Illness Neuroscience News https://neurosciencenews.com/statins-mental-health-10473/ A new study reveals statins, biguanides and other drugs that help treat physical conditions may have significant benefits for the treatment of bipolar disorder and schizophrenia. C:\Users\SarahCatanese\Zotero\storage\JVFXS6CL\statins-mental-health-10473.html

   edit   deselect   + to AI

 

journalArticle 2015 Cole, Jonathan C.; Green Bernacki, Carolyn; Helmer, Amanda; Pinninti, Narsimha; O’reardon, John P. Efficacy of Transcranial Magnetic Stimulation (TMS) in the Treatment of Schizophrenia: A Review of the Literature to Date Innovations in Clinical Neuroscience https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558786/ We reviewed the literature on transcranial magnetic stimulation and its uses and efficacy in schizophrenia. Multiple sources were examined on transcranial magnetic stimulation efficacy in relieving positive and negative symptoms of schizophrenia. Literature review was conducted via Ovid Medline and PubMed databases. We found multiple published studies and metaanalyses that give evidence that repetitive transcranial magnetic stimulation can have benefit in relieving positive and negative symptoms of schizophrenia, particularly auditory hallucinations. These findings should encourage the psychiatric community to expand research into other applications for

   edit   deselect   + to AI

 

which transcranial magnetic stimulation may be used to treat patients with psychiatric disability. Innov Clin Neurosci Efficacy of Transcranial Magnetic Stimulation (TMS) in the Treatment of Schizophrenia PubMed Central C:\Users\SarahCatanese\Zotero\storage\8AQN7I85\Cole et al. - 2015 - Efficacy of Transcranial Magnetic Stimulation (TMS.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558786/

   edit   deselect   + to AI

 

webpage Frontiers | Dorsolateral prefrontal cortex network properties are altered in schizophrenia: a TMS-EEG study https://www.frontiersin.org/10.3389/conf.fnhum.2013.212.00158/event_abstract Frontiers | Dorsolateral prefrontal cortex network properties are altered in schizophrenia

   edit   deselect   + to AI

 

journalArticle 2013 Coyle, Joseph T. Nitric Oxide and Symptom Reduction in Schizophrenia JAMA Psychiatry 10.1001/jamapsychiatry.2013.210 https://doi.org/10.1001/jamapsychiatry.2013.210 In this issue of the journal, Hallak et al report results from a placebo-controlled clinical trial showing that infusion of sodium nitroprusside causes a rapid and persistent reduction of symptoms in patients with schizophrenia who have been symptomatically stabilized with antipsychotic medications. The peer reviewers of the manuscript concurred that the study pointed to a potentially new avenue for pharmacologic intervention in schizophrenia, although they recognized that the small number of patients studied was a serious limitation. It is true that the field is littered with small trials with robust outcomes that ultimately are not replicated. However, the rationale for the study was tethered to an increasingly compelling body of evidence from drug challenges, postmortem analysis, and gene

   edit   deselect   + to AI

 

association studies that hypofunction of the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor subtype that mediates neural plasticity, is a core feature of schizophrenia. In particular, NMDA receptor hypofunction appears to be particularly relevant to negative symptoms and cognitive impairments in schizophrenia. JAMA Psychiatry Silverchair C:\Users\SarahCatanese\Zotero\storage\459WBS7W\1686036.html

   edit   deselect   + to AI

 

journalArticle 2015 Cole, Jonathan C.; Green Bernacki, Carolyn; Helmer, Amanda; Pinninti, Narsimha; O’reardon, John P. Efficacy of Transcranial Magnetic Stimulation (TMS) in the Treatment of Schizophrenia: A Review of the Literature to Date Innovations in Clinical Neuroscience https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558786/ We reviewed the literature on transcranial magnetic stimulation and its uses and efficacy in schizophrenia. Multiple sources were examined on transcranial magnetic stimulation efficacy in relieving positive and negative symptoms of schizophrenia. Literature review was conducted via Ovid Medline and PubMed databases. We found multiple published studies and metaanalyses that give evidence that repetitive transcranial magnetic stimulation can have benefit in relieving positive and negative symptoms of schizophrenia, particularly auditory hallucinations. These findings should encourage the psychiatric community to expand research into other applications for

   edit   deselect   + to AI

 

which transcranial magnetic stimulation may be used to treat patients with psychiatric disability. Innov Clin Neurosci Efficacy of Transcranial Magnetic Stimulation (TMS) in the Treatment of Schizophrenia PubMed Central C:\Users\SarahCatanese\Zotero\storage\SSNJRAVM\Cole et al. - 2015 - Efficacy of Transcranial Magnetic Stimulation (TMS.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558786/

   edit   deselect   + to AI

 

journalArticle 2018 Chang, Chuan-Chia; Tzeng, Nian-Sheng; Chao, Che-Yi; Yeh, Chin-Bin; Chang, Hsin-An The Effects of Add-on Fronto-Temporal Transcranial Direct Current Stimulation (tDCS) on Auditory Verbal Hallucinations, Other Psychopathological Symptoms, and Insight in Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Trial International Journal of Neuropsychopharmacology 10.1093/ijnp/pyy074 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209860/ Background The efficacy of fronto-temporal transcranial direct current stimulation in treating auditory verbal hallucinations and other psychopathological symptoms of schizophrenia patients has been examined in a small number of clinical trials with limited sample sizes, but the results are mixed. Fronto-temporal transcranial direct current stimulation has also been demonstrated to enhance patients’ insight into their mental illness in an open-label pilot study. The current investigation aimed to investigate the therapeutic effects

   edit   deselect   + to AI

 

of fronto-temporal transcranial direct current stimulation on the severity of auditory verbal hallucinations, other schizophrenia symptoms, and insight in a large double blind, randomized, sham-controlled trial. Methods Sixty patients with medication-refractory auditory verbal hallucinations were randomized over 2 conditions: transcranial direct current stimulation with 2-mA, twice-daily sessions for 5 consecutive days, with anodal stimulation to the left prefrontal cortex and cathodal stimulation to the left temporo-parietal junction, and sham treatment. Results Fronto-temporal transcranial direct current stimulation failed to cause significant changes in the severity of auditory verbal hallucinations and other schizophrenia symptoms. The levels of insight into illness (effect size=0.511, P<.001) and positive symptoms (effect size=0.781, P<.001) were largely promoted by 5 days of transcranial direct current stimulation relative to sham treatment. The beneficial effects on the 2

   edit   deselect   + to AI

 

insight dimensions remained 1 month after transcranial direct current stimulation. Conclusions Fronto-temporal transcranial direct current stimulation is not more effective for auditory verbal hallucinations and other schizophrenia symptoms than sham treatment. But the results of transcranial direct current stimulation-associated improvement in awareness of illness and positive symptoms show promise and provide a new direction for future research into insight promotion interventions in schizophrenia. Int J Neuropsychopharmacol The Effects of Add-on Fronto-Temporal Transcranial Direct Current Stimulation (tDCS) on Auditory Verbal Hallucinations, Other Psychopathological Symptoms, and Insight in Schizophrenia PubMed Central C:\Users\SarahCatanese\Zotero\storage\Q5BNRIFE\Chang et al. - 2018 - The Effects of Add-on Fronto-Temporal Transcranial.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209860/

   edit   deselect   + to AI

 

journalArticle 2018 Rohde, Christopher; Polcwiartek, Christoffer; Asztalos, Marton; Nielsen, Jimmi Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia: A Nation-Wide Register Study Schizophrenia Bulletin 10.1093/schbul/sbx043 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768038/ Objective: Negative symptoms and cognitive deficits are main features of schizophrenia but with limited treatment options. Earlier studies have suggested that central nervous system (CNS) stimulants have a small effect on these domains, but with inconclusive results. As the first study to date, we aimed to investigate whether CNS stimulants improve naturalistic outcomes (psychiatric admissions and antipsychotic use) in patients with schizophrenia. Methods: By using extensive health registers all patients with schizophrenia and their use of CNS stimulants in Denmark were identified. Two models were used to investigate the effectiveness of CNS stimulants in

   edit   deselect   + to AI

 

patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. Results: CNS stimulants use was associated with a reduction in number of psychiatric admissions from 3.43 (95% CI = 2.86 to 4.01) to 2.62 (95% CI = 1.99 to 3.25) (P = .009), with a more pronounced reduction for women (mean difference: −1.37, 95% CI = −2.34 to −0.40, P = .006). Psychiatric bed-days were reduced by 40 (95% CI = 24.5 to 55.6, P < .001) for individuals with at least 1 admission before CNS stimulant use. In addition, the total amount of antipsychotic use (Defined Daily Dose [DDD]) was reduced (P = .001). The Hazard rate ratio in psychiatric admissions between women taking CNS stimulants compared to women not taking CNS stimulants was 0.77 (95% CI = 0.67 to 0.88). Conclusion: CNS stimulants may have clinical potentials for improving functional

   edit   deselect   + to AI

 

outcomes in patients with schizophrenia and randomized clinical studies evaluating this topic are warranted. Schizophr Bull Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia PubMed Central ; C:\Users\SarahCatanese\Zotero\storage\QX7Q8S3F\Rohde et al. - 2018 - Effectiveness of Prescription-Based CNS Stimulants.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768038/

   edit   deselect   + to AI

 

journalArticle 2016 Shilling, Paul D.; Feifel, David Potential of Oxytocin in the Treatment of Schizophrenia CNS drugs 10.1007/s40263-016-0315-x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458113/ Schizophrenia is a heterogeneous, debilitating disorder characterized by three distinct sets of clinical features: positive symptoms, negative symptoms and cognitive deficits. Extant antipsychotic drugs have been most successful at treating the positive symptoms of patients that suffer from schizophrenia but have minimal therapeutic effects on negative symptoms and cognitive deficits, which are the symptoms that best predict the poor prognosis of these patients. Therefore, there has been a major effort towards identifying compounds that alleviate these symptoms., Oxytocin (OT) is a nonapeptide that regulates peripheral reproductive-relevant functions, and also acts as a neurotransmitter in the brain. Converging evidence from both preclinical and clinical research suggests that OT may have

   edit   deselect   + to AI

 

therapeutic efficacy for the positive symptoms, negative symptoms and cognitive deficits of schizophrenia. In the majority of the small-randomized placebo controlled clinical trials conducted to date, OT has shown particular promise in its potential to treat the intractable negative symptoms and social cognitive deficits exhibited by most of the patients with this debilitating disorder., In this leading article, we summarize the clinical evidence relevant to 1) endogenous OT and schizophrenia, and 2) the putative therapeutic effects of OT on each of the three clinical domains. CNS Drugs PubMed Central C:\Users\SarahCatanese\Zotero\storage\D4T97DBT\Shilling and Feifel - 2016 - Potential of Oxytocin in the Treatment of Schizoph.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458113/

   edit   deselect   + to AI

 

webpage 2017 Julapalli, Venu Tenet 6 (Continued): Health 3.0 is Antifragile — Hormesis in Health Care Medium https://medium.com/@vrjula/tenet-6-5-health-3-0-is-antifragile-hormesis-in-health-care-85b8c9e02d70 There is nothing more Finnish than a sauna. Tenet 6 (Continued) C:\Users\SarahCatanese\Zotero\storage\KHKCERN8\tenet-6-5-health-3-0-is-antifragile-hormesis-in-health-care-85b8c9e02d70.html

   edit   deselect   + to AI

 

journalArticle 2019 Palacios, Ensor Rafael; Isomura, Takuya; Parr, Thomas; Friston, Karl The emergence of synchrony in networks of mutually inferring neurons Scientific Reports 10.1038/s41598-019-42821-7 http://www.nature.com/articles/s41598-019-42821-7 Sci Rep DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\CXGPHNXN\Palacios et al. - 2019 - The emergence of synchrony in networks of mutually.pdf

   edit   deselect   + to AI

 

journalArticle 2015 Liedtka, Jeanne Perspective: Linking Design Thinking with Innovation Outcomes through Cognitive Bias Reduction Journal of Product Innovation Management https://doi.org/10.1111/jpim.12163 https://onlinelibrary.wiley.com/doi/abs/10.1111/jpim.12163 “Design thinking” has generated significant attention in the business press and has been heralded as a novel problem-solving methodology well suited to the often-cited challenges business organizations face in encouraging innovation and growth. Yet the specific mechanisms through which the use of design, approached as a thought process, might improve innovation outcomes have not received significant attention from business scholars. In particular, its utility has only rarely been linked to the academic literature on individual cognition and decision-making. This perspective piece advocates addressing this omission by examining “design thinking” as a practice potentially valuable for improving innovation outcomes by helping

   edit   deselect   + to AI

 

decision-makers reduce their individual level cognitive biases. In this essay, I first review the assumptions, principles, and key process tools associated with design thinking. I then establish its foundation in the decision-making literature, drawing on an extensive body of research on cognitive biases and their impact. The essay concludes by advancing a set of propositions and research implications, aiming to demonstrate one particular path that future research might take in assessing the utility of design thinking as a method for improving organizational outcomes related to innovation. In doing so, it seeks to address the challenge of conducting academic research on a practice that is obviously popular in management circles but appears resistant to rigorous empirical inquiry because of the multifaceted nature of its “basket” of tools and processes and the complexity of measuring the outcomes it produces. Perspective Wiley Online Library

   edit   deselect   + to AI

 

journalArticle 2021 Cuthbert, Bruce N.; Morris, Sarah E. Evolving Concepts of the Schizophrenia Spectrum: A Research Domain Criteria Perspective Frontiers in Psychiatry 10.3389/fpsyt.2021.641319 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947312/ Several trends intersecting over the past two decades have generated increasing debate as to how the concepts of schizophrenia, the schizophrenia spectrum, and the psychotic disorders spectrum should be regarded. These trends are reflected in various areas of research such as genomics, neuroimaging, and data-driven computational studies of multiple response systems. Growing evidence suggests that schizophrenia represents a broad and heterogenous syndrome, rather than a specific disease entity, that is part of a multi-faceted psychosis spectrum. Progress in explicating these various developments has been hampered by the dependence upon sets of symptoms and signs for determining a diagnosis, and by the reliance on traditional diagnostic

   edit   deselect   + to AI

 

categories in reviewing clinical research grants. To address these concerns, the U.S. National Institute of Mental Health initiated the Research Domain Criteria (RDoC) project, a translational research program that calls for studies designed in terms of empirically-based functions (such as cognitive control or reward learning) rather than diagnostic groups. RDoC is a research framework rather than an alternative diagnostic system, intended to provide data that can inform future nosological manuals. This commentary includes a brief summary of RDoC as it pertains to schizophrenia and psychotic spectra, examples of recent data that highlight the utility of the approach, and conclusions regarding the implications for evolving conceptualizations of serious mental illness. Front Psychiatry Evolving Concepts of the Schizophrenia Spectrum PubMed Central C:\Users\SarahCatanese\Zotero\storage\JMHXTISD\Cuthbert and Morris - 2021 - Evolving Concepts of the Schizophrenia Spectrum A.pdf;

   edit   deselect   + to AI

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947312/

   edit   deselect   + to AI

 

webpage The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia - ScienceDirect https://www.sciencedirect.com/science/article/abs/pii/S0193953X16000046?via%3Dihub C:\Users\SarahCatanese\Zotero\storage\WPNDWCG8\S0193953X16000046.html

   edit   deselect   + to AI

 

webpage Intranasal Oxytocin Reduces Negative Effects, Improves Cognitive Function in Schizophrenia - Psychiatry Advisor https://www.psychiatryadvisor.com/home/schizophrenia-advisor/intranasal-oxytocin-reduces-negative-effects-improves-cognitive-function-in-schizophrenia/ C:\Users\SarahCatanese\Zotero\storage\5SJ46R5R\intranasal-oxytocin-reduces-negative-effects-improves-cognitive-function-in-schizophrenia.html

   edit   deselect   + to AI

 

webpage MDMA in a Severely Disturbed Man with Psychosis, Administered by his Brother https://maps.org/research-archive/mdma/edsstory.html C:\Users\SarahCatanese\Zotero\storage\7LNKMT6T\edsstory.html

   edit   deselect   + to AI

 

journalArticle 2017 Donegan, Jennifer J.; Tyson, Jennifer A.; Branch, Sarah Y.; Beckstead, Michael J.; Anderson, Stewart A.; Lodge, Daniel J. Stem cell derived interneuron transplants as a treatment for schizophrenia: preclinical validation in a rodent model Molecular psychiatry 10.1038/mp.2016.121 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290293/ An increasing literature suggests that schizophrenia is associated with a reduction in hippocampal interneuron function. Thus, we posit that stem cell-derived interneuron transplants may be an effective therapeutic strategy to reduce hippocampal hyperactivity and attenuate behavioral deficits in schizophrenia. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of parvalbumin (PV)- or somatostatin (SST)-positive interneurons, which were transplanted into the ventral hippocampus of the methylazoxymethanol (MAM) rodent model of schizophrenia. These interneuron transplants integrate within the existing

   edit   deselect   + to AI

 

circuitry, reduce hippocampal hyperactivity, and normalize aberrant dopamine neuron activity. Further, interneuron transplants alleviate behaviors that model negative and cognitive symptoms, including deficits in social interaction and cognitive inflexibility. Interestingly, PV- and SST-enriched transplants produced differential effects on behavior, with PV-enriched populations effectively normalizing all the behaviors examined. These data suggest that stem cell-derived interneuron transplants may represent a novel therapeutic strategy for schizophrenia. Mol Psychiatry Stem cell derived interneuron transplants as a treatment for schizophrenia PubMed Central C:\Users\SarahCatanese\Zotero\storage\HBDT7GSZ\Donegan et al. - 2017 - Stem cell derived interneuron transplants as a tre.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290293/

   edit   deselect   + to AI

 

journalArticle 2019 Pape, Katrin; Tamouza, Ryad; Leboyer, Marion; Zipp, Frauke Immunoneuropsychiatry — novel perspectives on brain disorders Nature Reviews Neurology 10.1038/s41582-019-0174-4 https://www.nature.com/articles/s41582-019-0174-4 Immune processes have a vital role in CNS homeostasis, resilience and brain reserve. Our cognitive and social abilities rely on a highly sensitive and fine-tuned equilibrium of immune responses that involve both innate and adaptive immunity. Autoimmunity, chronic inflammation, infection and psychosocial stress can tip the scales towards disruption of higher-order networks. However, not only classical neuroinflammatory diseases, such as multiple sclerosis and autoimmune encephalitis, are caused by immune dysregulation that affects CNS function. Recent insight indicates that similar processes are involved in psychiatric diseases such as schizophrenia, autism spectrum disorder, bipolar disorder and depression. Pathways that are common to these

   edit   deselect   + to AI

 

disorders include microglial activation, pro-inflammatory cytokines, molecular mimicry, anti-neuronal autoantibodies, self-reactive T cells and disturbance of the blood–brain barrier. These discoveries challenge our traditional classification of neurological and psychiatric diseases. New clinical paths are required to identify subgroups of neuropsychiatric disorders that are phenotypically distinct but pathogenically related and to pave the way for mechanism-based immune treatments. Combined expertise from neurologists and psychiatrists will foster translation of these paths into clinical practice. The aim of this Review is to highlight outstanding findings that have transformed our understanding of neuropsychiatric diseases and to suggest new diagnostic and therapeutic criteria for the emerging field of immunoneuropsychiatry. www.nature.com C:\Users\SarahCatanese\Zotero\storage\Z7D622CJ\s41582-019-0174-4.html

   edit   deselect   + to AI

 

journalArticle 2020 Shukla, Rammohan; Henkel, Nicholas D.; Alganem, Khaled; Hamoud, Abdul-rizaq; Reigle, James; Alnafisah, Rawan S.; Eby, Hunter M.; Imami, Ali S.; Creeden, Justin; Miruzzi, Scott A.; Meller, Jaroslaw; Mccullumsmith, Robert E. Integrative Omics for Informed Drug Repurposing: Targeting CNS Disorders bioRxiv 10.1101/2020.04.24.060392 https://www.biorxiv.org/content/10.1101/2020.04.24.060392v1 <h3>Abstract</h3> <p>The treatment of CNS disorders, and in particular psychiatric illnesses, lacks disease-altering therapeutics for many conditions. This is likely due to regulatory challenges involving the high cost and slow-pace of drug development for CNS disorders as well as due to limited understanding of disease causality. Repurposing drugs for new indications have lower cost and shorter development timeline compared to that of de novo drug development. Historically, empirical drug-repurposing is a standard practice in psychiatry; however, recent advances in characterizing

   edit   deselect   + to AI

 

molecules with their structural and transcriptomic signatures along with ensemble of data analysis approaches, provides informed and cost-effective repurposing strategies that ameliorate the regulatory challenges. In addition, the potential to incorporate ontological approaches along with signature-based repurposing techniques addresses the various knowledge-based challenges associated with CNS drug development. In this review we primarily discuss signature-based <i>in silico</i> approaches to drug repurposing, and its integration with data science platforms for evidence-based drug repurposing. We contrast various <i>in silico</i> and empirical approaches and discuss possible avenues to improve the clinical relevance. These concepts provide a promising new translational avenue for developing new therapies for difficult to treat disorders, and offer the possibility of connecting drug discovery platforms and big data analytics with personalized disease signatures.</p> Integrative Omics

   edit   deselect   + to AI

 

for Informed Drug Repurposing www.biorxiv.org C:\Users\SarahCatanese\Zotero\storage\7DQWDL46\Shukla et al. - 2020 - Integrative Omics for Informed Drug Repurposing T.pdf; C:\Users\SarahCatanese\Zotero\storage\2PUCJJEP\2020.04.24.060392v1.html

   edit   deselect   + to AI

 

journalArticle 2019 Tenenbaum, Jessica D; Bhuvaneshwar, Krithika; Gagliardi, Jane P; Fultz Hollis, Kate; Jia, Peilin; Ma, Liang; Nagarajan, Radhakrishnan; Rakesh, Gopalkumar; Subbian, Vignesh; Visweswaran, Shyam; Zhao, Zhongming; Rozenblit, Leon Translational bioinformatics in mental health: open access data sources and computational biomarker discovery Briefings in Bioinformatics 10.1093/bib/bbx157 https://academic.oup.com/bib/article/20/3/842/4662948 Translational bioinformatics in mental health DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\KEZX66WS\Tenenbaum et al. - 2019 - Translational bioinformatics in mental health ope.pdf

   edit   deselect   + to AI

 

webpage Maps, Open Knowledge Overview of research on repositioning drugs, schizophrenia Open Knowledge Maps https://openknowledgemaps.org/map/91e762e38e94479cfa3ef0a59a802779 Get an overview of repositioning drugs, schizophrenia, find relevant papers, and identify important concepts. C:\Users\SarahCatanese\Zotero\storage\6PGVTGJC\91e762e38e94479cfa3ef0a59a802779.html

   edit   deselect   + to AI

 

journalArticle 2019 Karunakaran, Kalyani B.; Chaparala, Srilakshmi; Ganapathiraju, Madhavi K. Potentially repurposable drugs for schizophrenia identified from its interactome Scientific Reports 10.1038/s41598-019-48307-w https://www.nature.com/articles/s41598-019-48307-w We previously presented the protein-protein interaction network of schizophrenia associated genes, and from it, the drug-protein interactome which showed the drugs that target any of the proteins in the interactome. Here, we studied these drugs further to identify whether any of them may potentially be repurposable for schizophrenia. In schizophrenia, gene expression has been described as a measurable aspect of the disease reflecting the action of risk genes. We studied each of the drugs from the interactome using the BaseSpace Correlation Engine, and shortlisted those that had a negative correlation with differential gene expression of schizophrenia. This analysis resulted in 12 drugs whose differential gene

   edit   deselect   + to AI

 

expression (drug versus normal) had an anti-correlation with differential expression for schizophrenia (disorder versus normal). Some of these drugs were already being tested for their clinical activity in schizophrenia and other neuropsychiatric disorders. Several proteins in the protein interactome of the targets of several of these drugs were associated with various neuropsychiatric disorders. The network of genes with opposite drug-induced versus schizophrenia-associated expression profiles were significantly enriched in pathways relevant to schizophrenia etiology and GWAS genes associated with traits or diseases that had a pathophysiological overlap with schizophrenia. Drugs that targeted the same genes as the shortlisted drugs, have also demonstrated clinical activity in schizophrenia and other related disorders. This integrated computational analysis will help translate insights from the schizophrenia drug-protein interactome to clinical research - an important step, especially

   edit   deselect   + to AI

 

in the field of psychiatric drug development which faces a high failure rate. www.nature.com C:\Users\SarahCatanese\Zotero\storage\BRU7BA6S\Karunakaran et al. - 2019 - Potentially repurposable drugs for schizophrenia i.pdf; C:\Users\SarahCatanese\Zotero\storage\W3JG3PC8\s41598-019-48307-w.html

   edit   deselect   + to AI

 

journalArticle 2019 Kinon, Bruce J. The Group of Treatment Resistant Schizophrenias. Heterogeneity in Treatment Resistant Schizophrenia (TRS) Frontiers in Psychiatry 10.3389/fpsyt.2018.00757 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363683/ Schizophrenia is composed of a heterogeneous group of patient segments. Our current notion of the heterogeneity in schizophrenia is based on patients presenting with diverse disease symptom phenotypes, risk factors, structural and functional neuropathology, and a mixed range of expressed response to treatment. It is important for clinicians to recognize the various clinical presentations of resistance to treatment in schizophrenia and to understand how heterogeneity across treatment resistant patient segments may potentially inform new strategies for the development of effective treatments for Treatment Resistant Schizophrenia (TRS). The heterogeneity of schizophrenia may be reduced by parsing patient segments based on whether patients

   edit   deselect   + to AI

 

demonstrate an adequate or inadequate response to treatment. In our current concept of TRS, TRS is defined as non-response to at least two adequate trials of antipsychotic medication and is estimated to affect about 30% of all patients with schizophrenia. In this narrative review, the author discusses that the demonstration of inadequate response to antipsychotic drugs (APDs) may infer that some TRS patients may be suffering from a non-dopamine pathophysiology since D2 receptor antagonist-based treatment is ineffective. Preliminary neurobiological findings may further support the pathophysiologic distinction of TRS from that of general schizophrenia. Investigation of the basis for heterogeneity in TRS through the systematic investigation of relevant “clusters” of similarly at risk individuals may hopefully bring us closer to realize a precision medicine approach for developing effective therapies for TRS patient segments. Front Psychiatry PubMed Central

   edit   deselect   + to AI

 

C:\Users\SarahCatanese\Zotero\storage\XD8SCQE5\Kinon - 2019 - The Group of Treatment Resistant Schizophrenias. H.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363683/

   edit   deselect   + to AI

 

journalArticle 2015 Martínez, Víctor; Navarro, Carmen; Cano, Carlos; Fajardo, Waldo; Blanco, Armando DrugNet: network-based drug-disease prioritization by integrating heterogeneous data Artificial Intelligence in Medicine 10.1016/j.artmed.2014.11.003 OBJECTIVE: Computational drug repositioning can lead to a considerable reduction in cost and time in any drug development process. Recent approaches have addressed the network-based nature of biological information for performing complex prioritization tasks. In this work, we propose a new methodology based on heterogeneous network prioritization that can aid researchers in the drug repositioning process. METHODS: We have developed DrugNet, a new methodology for drug-disease and disease-drug prioritization. Our approach is based on a network-based prioritization method called ProphNet which has recently been developed by the authors. ProphNet is able to integrate data from complex networks involving a wide range of types of elements and

   edit   deselect   + to AI

 

interactions. In this work, we built a network of interconnected drugs, proteins and diseases and applied DrugNet to different types of tests for drug repositioning. RESULTS: We tested the performance of our approach on different validation tests, including cross validation and tests based on real clinical trials. DrugNet achieved a mean AUC value of 0.9552±0.0015 in 5-fold cross validation tests, and a mean AUC value of 0.8364 for tests based on recent clinical trials (phases 0-4) not present in our data. These results suggest that DrugNet could be very useful for discovering new drug uses. We also studied specific cases of particular interest, proving the benefits of heterogeneous data integration in this problem. CONCLUSIONS: Our methodology suggests that new drugs can be repositioned by generating ranked lists of drugs based on a given disease query or vice versa. Our study shows that the simultaneous integration of information about diseases, drugs and targets can lead to a

   edit   deselect   + to AI

 

significant improvement in drug repositioning tasks. DrugNet is available as a web tool from http://genome2.ugr.es/drugnet/ (accessed 23.09.14). Matlab source code is also available on the website. Artif Intell Med DrugNet PubMed http://www.ncbi.nlm.nih.gov/pubmed/25704113 Computational Biology; Humans; Models, Theoretical; Area Under Curve; Databases, Factual; Drug repositioning; Drug Repositioning; Reproducibility of Results; Computer Simulation; Data integration; Data Mining; Disease networks; Flow propagation; Network-based prioritization; ROC Curve; Systems Integration

   edit   deselect   + to AI

 

journalArticle 2018 Kauppi, Karolina; Rosenthal, Sara Brin; Lo, Min-Tzu; Sanyal, Nilotpal; Jiang, Mian; Abagyan, Ruben; McEvoy, Linda K; Andreassen, Ole A; Chen, Chi-Hua Revisiting antipsychotic drug actions through gene networks associated with schizophrenia The American journal of psychiatry 10.1176/appi.ajp.2017.17040410 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028303/ Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding of schizophrenia pathogenesis could shed light on actions of current drugs and reveal novel druggable pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks and uncover drug-disease relationships. Polygenic overlap between schizophrenia risk genes and antipsychotic drug targets has been demonstrated. However, the specific genes and pathways constituting this overlap are

   edit   deselect   + to AI

 

undetermined. Risk genes of polygenic disorders do not operate in isolation, but in combination with other genes. Thus, we utilized protein-protein interaction networks (interactome) to map antipsychotic drug targets (n=88) to networks of schizophrenia risk genes (n=328). Our results showed that schizophrenia risk genes were significantly localized in the interactome (p=0.0015), forming a distinct disease module. Core genes of the module were enriched for genes involved in developmental biology and cognition, which may have a central role in schizophrenia etiology. Intriguingly, antipsychotic drug targets overlapped with the core disease module and comprised multiple pathways beyond dopamine. Some important risk genes like CHRN, PCDH and HCN families were not connected to existing antipsychotics, but may be suitable targets for novel drugs or drug repurposing opportunities to treat other aspects of schizophrenia such as cognitive dysfunction and negative symptoms. This network

   edit   deselect   + to AI

 

medicine approach provides a platform to collate information of disease genetics and drug-gene interactions to shift focus from development of antipsychotics to multi-target anti-schizophrenia drugs. This approach is transferable to other diseases. Am J Psychiatry PubMed Central C:\Users\SarahCatanese\Zotero\storage\VIUKHRW8\Kauppi et al. - 2018 - Revisiting antipsychotic drug actions through gene.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028303/

   edit   deselect   + to AI

 

journalArticle 2015 Oliveira, Pedro; Zejnilovic, Leid; Canhão, Helena; von Hippel, Eric Innovation by patients with rare diseases and chronic needs Orphanet Journal of Rare Diseases 10.1186/s13023-015-0257-2 https://doi.org/10.1186/s13023-015-0257-2 We provide the first empirical exploration of disease-related innovation by patients and their caregivers. Our aims were to explore to what degree do patients develop innovative solutions; how many of these are unique developments; and do these solutions have positive perceived impact on the patients’ overall quality of life? In addition, we explored the factors associated with patient innovation development, and sharing of the solutions that the patients developed. Orphanet Journal of Rare Diseases BioMed Central C:\Users\SarahCatanese\Zotero\storage\HN5KGSKH\Oliveira et al. - 2015 - Innovation by patients with rare diseases and chro.pdf Diffusion of Innovation; Patient Innovation; Rare Diseases; User Innovation in Health

   edit   deselect   + to AI

 

webpage Programs • Karuna https://karunatx.com/programs/#pipeline C:\Users\SarahCatanese\Zotero\storage\VV4JA68J\programs.html

   edit   deselect   + to AI

 

book Alataş, Esra; Günay, Gamer Can Stem Cell Transplant Be a New Alternative in the Treatment of Schizophrenia? Until recently, it was thought that there is no neuronal regeneration and neuron loss is irreversible, but today the exist-ence of neural regeneration and neural plasticity have been documented. The effectiveness of stem cell treatment in nu-merous degenerative diseases, as well as some neurodegenerative diseases, has created hopes toward the use of stem cell treatment in schizophrenia, which is a disease that progresses with neuronal degeneration and loss of neurons, and is characterized with worsening clinical outcomes and impairment. CiteSeer C:\Users\SarahCatanese\Zotero\storage\XCBE8R28\Alataş and Günay - Can Stem Cell Transplant Be a New Alternative in t.pdf; C:\Users\SarahCatanese\Zotero\storage\ZGYHNTIE\summary.html

   edit   deselect   + to AI

 

journalArticle 2014 Clark, Vincent P.; Parasuraman, Raja Neuroenhancement: Enhancing brain and mind in health and in disease NeuroImage 10.1016/j.neuroimage.2013.08.071 http://www.sciencedirect.com/science/article/pii/S1053811913009385 Humans have long used cognitive enhancement methods to expand the proficiency and range of the various mental activities that they engage in, including writing to store and retrieve information, and computers that allow them to perform myriad activities that are now commonplace in the internet age. Neuroenhancement describes the use of neuroscience-based techniques for enhancing cognitive function by acting directly on the human brain and nervous system, altering its properties to increase performance. Cognitive neuroscience has now reached the point where it may begin to put theory derived from years of experimentation into practice. This special issue includes 16 articles that employ or examine a variety of neuroenhancement methods currently being

   edit   deselect   + to AI

 

developed to increase cognition in healthy people and in patients with neurological or psychiatric illness. This includes transcranial electromagnetic stimulation methods, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), along with deep brain stimulation, neurofeedback, behavioral training techniques, and these and other techniques in conjunction with neuroimaging. These methods can be used to improve attention, perception, memory and other forms of cognition in healthy individuals, leading to better performance in many aspects of everyday life. They may also reduce the cost, duration and overall impact of brain and mental illness in patients with neurological and psychiatric illness. Potential disadvantages of these techniques are also discussed. Given that the benefits of neuroenhancement outweigh the potential costs, these methods could potentially reduce suffering and improve quality of life for everyone, while further increasing

   edit   deselect   + to AI

 

our knowledge about the mechanisms of human cognition. NeuroImage Neuroenhancement ScienceDirect C:\Users\SarahCatanese\Zotero\storage\FU8JX3LD\Clark and Parasuraman - 2014 - Neuroenhancement Enhancing brain and mind in heal.pdf; C:\Users\SarahCatanese\Zotero\storage\T6NXJJ5X\S1053811913009385.html

   edit   deselect   + to AI

 

webpage Our Team | The Rothfeld Center | Waltham, MA copy-of-rcworkup https://www.rothfeldcenter.com/about The Rothfeld Center for Integrative Medicine has expertly trained practitioners including integrative doctors, nurses, and clinical staff. C:\Users\SarahCatanese\Zotero\storage\T3AXDUQR\about.html

   edit   deselect   + to AI

 

journalArticle 2014 Ahnaou, A.; Huysmans, H.; Jacobs, T.; Drinkenburg, W. H. I. M. Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential Neuropharmacology 10.1016/j.neuropharm.2014.08.015 http://www.sciencedirect.com/science/article/pii/S0028390814002986 Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist

   edit   deselect   + to AI

 

scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations. Cognition enhancers elicited systematic (“fingerprint”) enhancement of cortical slow theta (4.5–6 Hz) and gamma (30.5–50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma

   edit   deselect   + to AI

 

oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to assess efficacy of novel therapeutic drugs with cognition enhancing potential. Neuropharmacology ScienceDirect C:\Users\SarahCatanese\Zotero\storage\AXI6VZRX\S0028390814002986.html Animal model; Cognition enhancers; Coherent functional network; EEG oscillations; Neurodegenerative disorders; Translational biomarker

   edit   deselect   + to AI

 

journalArticle 2020 Tong, Jing; Kong, Chao; Wang, Xin; Liu, Huanhuan; Li, Baike; He, Yuying Transcranial direct current stimulation influences bilingual language control mechanism: evidence from cross-frequency coupling Cognitive Neurodynamics 10.1007/s11571-019-09561-w https://doi.org/10.1007/s11571-019-09561-w How to better suppress the interference from the non-target language when switching from one language to the other in bilingual production? The current study applied transcranial direct current stimulation over the right dorsolateral prefrontal cortex to modulate language control measured by cross-frequency coupling. We found that switching to L2 was more modulated by F4–F3 alpha–beta phase-amplitude compared to switching to L1 after receiving the anodal stimulation at the language task schema phase. These findings suggest that anodal stimulation affects the selection of the target language task schema by enhancing the activation of frontal areas and facilitating the

   edit   deselect   + to AI

 

coordination between the left and the right frontal hemispheres. Cogn Neurodyn Transcranial direct current stimulation influences bilingual language control mechanism Springer Link

   edit   deselect   + to AI

 

journalArticle 2020 Swyer, Ariel; Powers, Albert R. Voluntary control of auditory hallucinations: phenomenology to therapeutic implications npj Schizophrenia 10.1038/s41537-020-0106-8 https://www.nature.com/articles/s41537-020-0106-8 Auditory verbal hallucinations (AVH) have traditionally been thought to be outside the influence of conscious control. However, recent work with voice hearers makes clear that both treatment-seeking and non-treatment-seeking voice hearers may exert varying degrees of control over their voices. Evidence suggests that this ability may be a key factor in determining health status, but little systematic examination of control in AVH has been carried out. This review provides an overview of the research examining control over AVH in both treatment-seeking and non-treatment-seeking populations. We first examine the relationship between control over AVH and health status as well as the psychosocial factors that may influence control and functioning. We then

   edit   deselect   + to AI

 

link control to various cognitive constructs that appear to be important for voice hearing. Finally, we reconcile the possibility of control with the field’s current understanding of the proposed cognitive, computational, and neural underpinnings of hallucinations and perception more broadly. Established relationships between control, health status, and functioning suggest that the development of control over AVH could increase functioning and reduce distress. A more detailed understanding of the discrete types of control, their development, and their neural underpinnings is essential for translating this knowledge into new therapeutic approaches. Voluntary control of auditory hallucinations www.nature.com C:\Users\SarahCatanese\Zotero\storage\LC9ZF9R4\Swyer and Powers - 2020 - Voluntary control of auditory hallucinations phen.pdf; C:\Users\SarahCatanese\Zotero\storage\L8SWSAEG\s41537-020-0106-8.html

   edit   deselect   + to AI

 

journalArticle 2020 Myers, John C.; Mock, Jeffrey R.; Golob, Edward J. Sensorimotor Integration Can Enhance Auditory Perception Scientific Reports 10.1038/s41598-020-58447-z https://www.nature.com/articles/s41598-020-58447-z Whenever we move, speak, or play musical instruments, our actions generate auditory sensory input. The sensory consequences of our actions are thought to be predicted via sensorimotor integration, which involves anatomical and functional links between auditory and motor brain regions. The physiological connections are relatively well established, but less is known about how sensorimotor integration affects auditory perception. The sensory attenuation hypothesis suggests that the perceived loudness of self-generated sounds is attenuated to help distinguish self-generated sounds from ambient sounds. Sensory attenuation would work for louder ambient sounds, but could lead to less accurate perception if the ambient sounds were quieter. We hypothesize that a key

   edit   deselect   + to AI

 

function of sensorimotor integration is the facilitated processing of self-generated sounds, leading to more accurate perception under most conditions. The sensory attenuation hypothesis predicts better performance for higher but not lower intensity comparisons, whereas sensory facilitation predicts improved perception regardless of comparison sound intensity. A series of experiments tested these hypotheses, with results supporting the enhancement hypothesis. Overall, people were more accurate at comparing the loudness of two sounds when making one of the sounds themselves. We propose that the brain selectively modulates the perception of self-generated sounds to enhance representations of action consequences. www.nature.com C:\Users\SarahCatanese\Zotero\storage\A7RRWVK6\Myers et al. - 2020 - Sensorimotor Integration Can Enhance Auditory Perc.pdf; C:\Users\SarahCatanese\Zotero\storage\KVREA7IF\s41598-020-58447-z.html

   edit   deselect   + to AI

 

journalArticle 2015 Guastella, Adam J.; Ward, Philip B.; Hickie, Ian B.; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M.; Langdon, Robyn A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia Schizophrenia Research 10.1016/j.schres.2015.06.005 http://www.sciencedirect.com/science/article/pii/S0920996415003205 Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved

   edit   deselect   + to AI

 

higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in

   edit   deselect   + to AI

 

a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Schizophrenia Research ScienceDirect C:\Users\SarahCatanese\Zotero\storage\Z7QYR59G\S0920996415003205.html Emotion recognition; Hormone; Neuropeptides; Psychosis; Social behavior

   edit   deselect   + to AI

 

journalArticle 2012 MacCabe, James H.; Brébion, Gildas; Reichenberg, Abraham; Ganguly, Taposhri; McKenna, Peter J.; Murray, Robin M.; David, Anthony S. Superior intellectual ability in schizophrenia: Neuropsychological characteristics. Neuropsychology 10.1037/a0026376 http://doi.apa.org/getdoi.cfm?doi=10.1037/a0026376 Objective: It has been suggested that neurocognitive impairment is a core deficit in schizophrenia. However, it appears that some patients with schizophrenia have intelligence quotients (IQs) in the superior range. In this study, we sought out schizophrenia patients with an estimated premorbid Intelligence Quotient (IQ) of at least 115 and studied their neuropsychological profile. Method: Thirty-four patients meeting diagnostic criteria for schizophrenia or schizoaffective disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM–IV), with mean estimated premorbid IQ of 120, were recruited and divided into two subgroups, according

   edit   deselect   + to AI

 

to whether or not their IQ had declined by at least 10 points from their premorbid estimate. Their performance on an extensive neuropsychological battery was compared with that of 19 IQ-matched healthy controls and a group of 16 “typical” schizophrenia patients with estimated premorbid IQ Ͻ110, using one way ANOVAs and profile analysis using MANOVAs. Results: Schizophrenia patients whose estimated premorbid and current IQ both lay in the superior range were statistically indistinguishable from IQ-matched healthy controls on all neurocognitive tests. However, their profile of relative performance in subtests was similar to that of typical schizophrenia patients. Patients with superior premorbid IQ and evidence of intellectual deterioration had intermediate scores. Conclusions: Our results confirm the existence of patients meeting DSM–IV diagnostic criteria for schizophrenia who have markedly superior premorbid intellectual level and appear to be free of gross neuropsychological

   edit   deselect   + to AI

 

deficits. We discuss the implications of these findings for the primacy of cognitive deficits in schizophrenia. Neuropsychology Superior intellectual ability in schizophrenia DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\P3H22MN5\MacCabe et al. - 2012 - Superior intellectual ability in schizophrenia Ne.pdf

   edit   deselect   + to AI

 

journalArticle 2021 Ľupták, Matej; Michaličková, Danica; Fišar, Zdeněk; Kitzlerová, Eva; Hroudová, Jana Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets World Journal of Psychiatry 10.5498/wjp.v11.i7.277 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311514/ Schizophrenia is a severe psychiatric disorder characterized by emotional, behavioral and cognitive disturbances, and the treatment of schizophrenia is often complicated by noncompliance and pharmacoresistance. The search for the pathophysiological mechanisms underlying schizophrenia has resulted in the proposal of several hypotheses to explain the impacts of environmental, genetic, neurodevelopmental, immune and inflammatory factors on disease onset and progression. This review discusses the newest insights into the pathophysiology of and risk factors for schizophrenia and notes novel approaches in antipsychotic treatment and potential diagnostic and theranostic biomarkers. The current

   edit   deselect   + to AI

 

hypotheses focusing on neuromediators (dopamine, glutamate, and serotonin), neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, and oxidative stress are summarized. Key genetic features, including small nucleotide polymorphisms, copy number variations, microdeletions, mutations and epigenetic changes, are highlighted. Current pharmacotherapy of schizophrenia relies mostly on dopaminergic and serotonergic antagonists/partial agonists, but new findings in the pathophysiology of schizophrenia have allowed the expansion of novel approaches in pharmacotherapy and the establishment of more reliable biomarkers. Substances with promising results in preclinical and clinical studies include lumateperone, pimavanserin, xanomeline, roluperidone, agonists of trace amine-associated receptor 1, inhibitors of glycine transporters, AMPA allosteric modulators, mGLUR2-3 agonists, D-amino acid oxidase inhibitors and cannabidiol. The use of anti-inflammatory agents as an add-on

   edit   deselect   + to AI

 

therapy is mentioned. World J Psychiatry PubMed Central C:\Users\SarahCatanese\Zotero\storage\8Y59AMZP\Ľupták et al. - 2021 - Novel approaches in schizophrenia-from risk factor.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311514/

   edit   deselect   + to AI

 

journalArticle 2020 Rutigliano, Grazia; Zucchi, Riccardo Molecular Variants in Human Trace Amine-Associated Receptors and Their Implications in Mental and Metabolic Disorders Cellular and Molecular Neurobiology 10.1007/s10571-019-00743-y http://link.springer.com/10.1007/s10571-019-00743-y We provide a comprehensive review of the available evidence on the pathophysiological implications of genetic variants in the human trace amine-associated receptor (TAAR) superfamily. Genes coding for trace amine-associated receptors (taars) represent a multigene family of G-protein-coupled receptors, clustered to a small genomic region of 108 kb located in chromosome 6q23, which has been consistently identified by linkage analyses as a susceptibility locus for schizophrenia and affective disorders. Most TAARs are expressed in brain areas involved in emotions, reward and cognition. TAARs are activated by endogenous trace amines and thyronamines, and evidence for a modulatory action on other

   edit   deselect   + to AI

 

monaminergic systems has been reported. Therefore, linkage analyses were followed by fine mapping association studies in schizophrenia and affective disorders. However, none of these reports has received sufficient universal replication, so their status remains uncertain. Single nucleotide polymorphisms in taars have emerged as susceptibility loci from genome-wide association studies investigating migraine and brain development, but none of the detected variants reached the threshold for genome-wide significance. In the last decade, technological advances enabled single-gene or whole-exome sequencing, thus allowing the detection of rare genetic variants, which may have a greater impact on the risk of complex disorders. Using these approaches, several taars (especially taar1) variants have been detected in patients with mental and metabolic disorders, and in some cases, defective receptor function has been demonstrated in vitro. Finally, with the use of transcriptomic and peptidomic

   edit   deselect   + to AI

 

techniques, dysregulations of TAARs (especially TAAR6) have been identified in brain disorders characterized by cognitive impairment. Cell Mol Neurobiol DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\EB6GBBZC\Rutigliano and Zucchi - 2020 - Molecular Variants in Human Trace Amine-Associated.pdf

   edit   deselect   + to AI

 

journalArticle 2021 Kantrowitz, Joshua T. Trace Amine-Associated Receptor 1 as a Target for the Development of New Antipsychotics: Current Status of Research and Future Directions CNS Drugs 10.1007/s40263-021-00864-3 https://doi.org/10.1007/s40263-021-00864-3 Schizophrenia is a mental illness associated with an array of symptoms that often result in disability. The primary treatments for schizophrenia are termed antipsychotics. Although antipsychotics modulate a number of different receptor types and subtypes, all currently regulatory agency-approved antipsychotics share in common direct or functional antagonism at the dopamine type 2 receptor (D2R). The majority of people with schizophrenia do not achieve full resolution of their symptoms with antipsychotics, suggesting the need for alternative or complementary approaches. The primary focus of this review is to assess the evidence for the role of the trace amine-associated receptor 1 (TAAR-1) in schizophrenia and the role of TAAR-1

   edit   deselect   + to AI

 

modulators as novel-mechanism antipsychotics. Topics include an overview of TAAR-1 physiology and pathophysiology in schizophrenia, interaction with other neurotransmitter systems, including the dopaminergic, glutamatergic and serotonergic system, and finally, a review of investigational TAAR-1 compounds that have reached Phase II clinical studies in schizophrenia: SEP-363856 (ulotaront) and RO6889450 (ralmitaront). Thus far, results are publicly available only for ulotaront in a relatively young (18–40 years) and acutely exacerbated cohort. These results showed positive effects for overall schizophrenia symptoms without significant tolerability concerns. An ongoing study of ralmitaront will assess specific efficacy in patients with persistent negative symptoms. If trials of TAAR-1 modulators, and other novel-mechanism targets for schizophrenia that are under active study, continue to show positive results, the definition of an antipsychotic may need to be expanded beyond the D2R

   edit   deselect   + to AI

 

target in the near future. CNS Drugs Trace Amine-Associated Receptor 1 as a Target for the Development of New Antipsychotics Springer Link

   edit   deselect   + to AI

 

webpage Schizophrenia treatments: a stagnant field on the cusp of change? https://www.clinicaltrialsarena.com/analysis/schizophrenia-treatments/ C:\Users\SarahCatanese\Zotero\storage\6N4T7RGU\schizophrenia-treatments.html

   edit   deselect   + to AI

 

webpage Publications OLSON RESEARCH GROUP https://www.olsonlab.org/publications.html Publications After 7/1/15 C:\Users\SarahCatanese\Zotero\storage\3IKNIPRT\publications.html

   edit   deselect   + to AI

 

journalArticle 2021 Olson, David E. The Promise of Psychedelic Science ACS Pharmacology & Translational Science 10.1021/acsptsci.1c00071 https://doi.org/10.1021/acsptsci.1c00071 ACS Pharmacol. Transl. Sci. ACS Publications C:\Users\SarahCatanese\Zotero\storage\CG5LTTFS\acsptsci.html; C:\Users\SarahCatanese\Zotero\storage\DH8UFJ39\Olson - 2021 - The Promise of Psychedelic Science.pdf

   edit   deselect   + to AI

 

journalArticle Kim, Saehyeon; Okazaki, Satoshi; Otsuka, Ikuo; Shinko, Yutaka; Horai, Tadasu; Shimmyo, Naofumi; Hirata, Takashi; Yamaki, Naruhisa; Tanifuji, Takaki; Boku, Shuken; Sora, Ichiro; Hishimoto, Akitoyo Searching for biomarkers in schizophrenia and psychosis: Case-control study using capillary electrophoresis and liquid chromatography time-of-flight mass spectrometry and systematic review for biofluid metabolites Neuropsychopharmacology Reports 10.1002/npr2.12223 https://onlinelibrary.wiley.com/doi/abs/10.1002/npr2.12223 Metabolomics has been attracting attention in recent years as an objective method for diagnosing schizophrenia. In this study, we analyzed 378 metabolites in the serum of schizophrenia patients using capillary electrophoresis- and liquid chromatography-time-of-flight mass spectrometry. Using multivariate analysis with the orthogonal partial least squares method, we observed significantly higher levels of alanine, glutamate, lactic acid, ornithine, and serine

   edit   deselect   + to AI

 

and significantly lower levels of urea, in patients with chronic schizophrenia compared to healthy controls. Additionally, levels of fatty acids (15:0), (17:0), and (19:1), cis-11-eicosenoic acid, and thyroxine were significantly higher in patients with acute psychosis than in those in remission. Moreover, we conducted a systematic review of comprehensive metabolomics studies on schizophrenia over the last 20 years and observed consistent trends of increase in some metabolites such as glutamate and glucose, and decrease in citrate in schizophrenia patients across several studies. Hence, we provide substantial evidence for metabolic biomarkers in schizophrenia patients through our metabolomics study. Searching for biomarkers in schizophrenia and psychosis Wiley Online Library C:\Users\SarahCatanese\Zotero\storage\JP9LNYLC\Kim et al. - Searching for biomarkers in schizophrenia and psyc.pdf; C:\Users\SarahCatanese\Zotero\storage\UC7VWZS8\npr2.html schizophrenia; systematic review;

   edit   deselect   + to AI

 

psychosis; biomarkers; metabolomics

   edit   deselect   + to AI

 

journalArticle 2018 Szilágyi, Bence; Ferenczy, György G.; Keserű, György M. Drug discovery strategies and the preclinical development of D-amino-acid oxidase inhibitors as antipsychotic therapies Expert Opinion on Drug Discovery 10.1080/17460441.2018.1524459 https://doi.org/10.1080/17460441.2018.1524459 Introduction: D-amino-acid oxidase (DAAO) degrades D-serine, a co-agonist of the NMDA receptor whose dysfunction is involved in the positive, negative, and cognitive symptoms of schizophrenia. The inhibition of DAAO appears to be a viable strategy to increase D-serine level and to have therapeutic potential in schizophrenia.Areas covered: This review describes the efforts to develop DAAO inhibitors and to optimize their in vitro and in vivo effects in preclinical settings. The structural evolution of DAAO inhibitors is presented from simple carboxylic acid derivatives via small, planar compounds with carboxylic acid mimetics to extended compounds whose binding is possible owing to

   edit   deselect   + to AI

 

DAAO flexibility. Inhibitory potency and pharmacokinetic properties are discussed in the context of compounds’ ability to increase D-serine level and to show efficacy in animal models of schizophrenia.Expert opinion: The accumulated knowledge on the structural requirements of DAAO inhibitors and on their in vitro and in vivo effects provides appropriate basis to develop inhibitors with optimized potency, selectivity and pharmacokinetic profile including blood-brain penetration. In addition, the validation of DAAO inhibition therapy in alleviating the symptoms of schizophrenia requires further studies on the efficacy of DAAO inhibitors in behavioral assays of animals and on the species differences in D-serine metabolism. Taylor and Francis+NEJM C:\Users\SarahCatanese\Zotero\storage\3SXVAMAQ\17460441.2018.html schizophrenia; D-amino-acid oxidase; D-serine

   edit   deselect   + to AI

 

webpage Neuropsychiatric Drug Developers Show a Renewed Sense of Purpose: Therapeutics for depression, schizophrenia, and other neuropsychiatric disorders are targeting inflammation, stimulating neurogenesis, and taking cues from biomarkers: Genetic Engineering & Biotechnology News: Vol 41, No 11 https://www.liebertpub.com/doi/10.1089/gen.41.11.13

   edit   deselect   + to AI

 

journalArticle 2017 Krystal, John H.; Murray, John D.; Chekroud, Adam M.; Corlett, Philip R.; Yang, Genevieve; Wang, Xiao-Jing; Anticevic, Alan Computational Psychiatry and the Challenge of Schizophrenia Schizophrenia Bulletin 10.1093/schbul/sbx025 Schizophrenia research is plagued by enormous challenges in integrating and analyzing large datasets and difficulties developing formal theories related to the etiology, pathophysiology, and treatment of this disorder. Computational psychiatry provides a path to enhance analyses of these large and complex datasets and to promote the development and refinement of formal models for features of this disorder. This presentation introduces the reader to the notion of computational psychiatry and describes discovery-oriented and theory-driven applications to schizophrenia involving machine learning, reinforcement learning theory, and biophysically-informed neural circuit models. Schizophr Bull PubMed

   edit   deselect   + to AI

 

C:\Users\SarahCatanese\Zotero\storage\2J4KUBSX\Krystal et al. - 2017 - Computational Psychiatry and the Challenge of Schi.pdf; http://www.ncbi.nlm.nih.gov/pubmed/28338845 schizophrenia; Schizophrenia; Computational Biology; Humans; machine learning; computational neuroscience; computational psychiatry; delusions; medication selection; Neurosciences; Psychiatry; working memory

   edit   deselect   + to AI

 

journalArticle 2020 Apryatin, Sergey A.; Алексеевич, Апрятин Сергей; Karpenko, Marina N.; Николаевна, Карпенко Марина; Muruzheva, Zamira M.; Магомедовна, Муружева Замира; Bolshakova, Maria V.; Валерьевна, Большакова Мария; Magazenkova, Daria N.; Николаевна, Магазенкова Дарья; Klimenko, Victor M.; Матвеевич, Клименко Виктор Neurodegenerative and metabolic disorders, mediated by the trace amines and their receptors Medical academic journal 10.17816/MAJ25746 https://doi.org/10.17816/MAJ25746 The aim of the study is the modern scientific literature estimation in the field of the investigation of neurodegenerative and metabolic disorders mediated by the trace amines and their receptors. The analysis of modern ideas about the “feedback” of neurodegenerative and metabolic diseases in which the trace amines and their receptors are involved was carried out. The important role of trace amines and their receptors in the regulation of the dopamine system, in connection with metabolic and

   edit   deselect   + to AI

 

neurodegenerative diseases, including Parkinson's disease, ADHD, schizophrenia, obesity, metabolic syndrome and other pathological conditions, has been shown. Trace amines and their receptors have a direct effect on dopamine systems, being regulators of various metabolic and neurodegenerative processes, participating in energy metabolism, neurogenesis,and other vital processes. journals-eco--vector-com.translate.goog C:\Users\SarahCatanese\Zotero\storage\EYPZUMWU\Apryatin et al. - 2020 - Neurodegenerative and metabolic disorders, mediate.pdf neurodegenerative and metabolic diseases; trace amines; trace amines receptors; нейродегенеративные и метаболические заболевания; рецепторы следовых аминов; следовые амины

   edit   deselect   + to AI

 

journalArticle 2013 Revel, F. G.; Moreau, J.-L.; Pouzet, B.; Mory, R.; Bradaia, A.; Buchy, D.; Metzler, V.; Chaboz, S.; Groebke Zbinden, K.; Galley, G.; Norcross, R. D.; Tuerck, D.; Bruns, A.; Morairty, S. R.; Kilduff, T. S.; Wallace, T. L.; Risterucci, C.; Wettstein, J. G.; Hoener, M. C. A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight Molecular Psychiatry 10.1038/mp.2012.57 https://www.nature.com/articles/mp201257 Schizophrenia is a chronic, severe and highly complex mental illness. Current treatments manage the positive symptoms, yet have minimal effects on the negative and cognitive symptoms, two prominent features of the disease with critical impact on the long-term morbidity. In addition, antipsychotic treatments trigger serious side effects that precipitate treatment discontinuation. Here, we show that activation of the trace amine-associated receptor 1 (TAAR1), a modulator of

   edit   deselect   + to AI

 

monoaminergic neurotransmission, represents a novel therapeutic option. In rodents, activation of TAAR1 by two novel and pharmacologically distinct compounds, the full agonist RO5256390 and the partial agonist RO5263397, blocks psychostimulant-induced hyperactivity and produces a brain activation pattern reminiscent of the antipsychotic drug olanzapine, suggesting antipsychotic-like properties. TAAR1 agonists do not induce catalepsy or weight gain; RO5263397 even reduced haloperidol-induced catalepsy and prevented olanzapine from increasing body weight and fat accumulation. Finally, TAAR1 activation promotes vigilance in rats and shows pro-cognitive and antidepressant-like properties in rodent and primate models. These data suggest that TAAR1 agonists may provide a novel and differentiated treatment of schizophrenia as compared with current medication standards: TAAR1 agonists may improve not only the positive symptoms but also the negative symptoms and cognitive deficits, without

   edit   deselect   + to AI

 

causing adverse effects such as motor impairments or weight gain. Mol Psychiatry A new perspective for schizophrenia www.nature.com C:\Users\SarahCatanese\Zotero\storage\9AS8HN9Q\Revel et al. - 2013 - A new perspective for schizophrenia TAAR1 agonist.pdf; C:\Users\SarahCatanese\Zotero\storage\9DWNR9ZL\mp201257.html Schizophrenia; Drug therapy; G protein-coupled receptors

   edit   deselect   + to AI

 

journalArticle 2021 Kantrowitz, Joshua T. Trace Amine-Associated Receptor 1 as a Target for the Development of New Antipsychotics: Current Status of Research and Future Directions CNS drugs 10.1007/s40263-021-00864-3 Schizophrenia is a mental illness associated with an array of symptoms that often result in disability. The primary treatments for schizophrenia are termed antipsychotics. Although antipsychotics modulate a number of different receptor types and subtypes, all currently regulatory agency-approved antipsychotics share in common direct or functional antagonism at the dopamine type 2 receptor (D2R). The majority of people with schizophrenia do not achieve full resolution of their symptoms with antipsychotics, suggesting the need for alternative or complementary approaches. The primary focus of this review is to assess the evidence for the role of the trace amine-associated receptor 1 (TAAR-1) in schizophrenia and the role of TAAR-1 modulators as novel-mechanism

   edit   deselect   + to AI

 

antipsychotics. Topics include an overview of TAAR-1 physiology and pathophysiology in schizophrenia, interaction with other neurotransmitter systems, including the dopaminergic, glutamatergic and serotonergic system, and finally, a review of investigational TAAR-1 compounds that have reached Phase II clinical studies in schizophrenia: SEP-363856 (ulotaront) and RO6889450 (ralmitaront). Thus far, results are publicly available only for ulotaront in a relatively young (18-40 years) and acutely exacerbated cohort. These results showed positive effects for overall schizophrenia symptoms without significant tolerability concerns. An ongoing study of ralmitaront will assess specific efficacy in patients with persistent negative symptoms. If trials of TAAR-1 modulators, and other novel-mechanism targets for schizophrenia that are under active study, continue to show positive results, the definition of an antipsychotic may need to be expanded beyond the D2R target in the near future. CNS

   edit   deselect   + to AI

 

Drugs Trace Amine-Associated Receptor 1 as a Target for the Development of New Antipsychotics PubMed http://www.ncbi.nlm.nih.gov/pubmed/34655036

   edit   deselect   + to AI

 

journalArticle 2021 Guynn, Michael Optogenetics and Controlling the Human Mind Curiosity: Interdisciplinary Journal of Research and Innovation 10.36898/001c.28096 https://curiosity.scholasticahq.com/article/28096-optogenetics-and-controlling-the-human-mind From the dawn of history to modern times humans have been using knowledge of neural structures to alter behavior (Faria, 2013). In modern times brain stimulation experiments have been conducted on animals and even humans to control the mind (Marzullo, 2017; Bishop et al., 1963). Behavioral psychologist B.F. Skinner proposed that all behavior can be controlled using rewards and punishments (Schultz & Schultz, 2019). A new technology in neural engineering known as optogenetics uses CRISPR Cas-9 to genetically modify human neurons to express photosensitive opsins and thus fire when stimulated by certain light wavelengths (Boyden, 2011). Optogenetics offers greater spatial and temporal control of brain activity than current

   edit   deselect   + to AI

 

technologies like transcranial magnetic stimulation or psychopharmacological drugs (Williams and Entcheva, 2015; Deisseroth et al., 2006; Shao et al., 2018). The ethics of potential side effects, invasiveness, and abuse should be taken into consideration before human trials begin in the near future (Mathews, 2011; Gilbert, Harris, & Kidd, 2021). Curiosity curiosity.scholasticahq.com C:\Users\SarahCatanese\Zotero\storage\3J9ZQNCE\Guynn - 2021 - Optogenetics and Controlling the Human Mind.pdf; C:\Users\SarahCatanese\Zotero\storage\C4PCLAWD\28096-optogenetics-and-controlling-the-human-mind.html

   edit   deselect   + to AI

 

journalArticle 2021 Bloomingdale, Peter; Karelina, Tatiana; Cirit, Murat; Muldoon, Sarah F.; Baker, Justin; McCarty, William J.; Geerts, Hugo; Macha, Sreeraj Quantitative systems pharmacology in neuroscience: Novel methodologies and technologies CPT: Pharmacometrics & Systems Pharmacology 10.1002/psp4.12607 https://onlinelibrary.wiley.com/doi/abs/10.1002/psp4.12607 The development and application of quantitative systems pharmacology models in neuroscience have been modest relative to other fields, such as oncology and immunology, which may reflect the complexity of the brain. Technological and methodological advancements have enhanced the quantitative understanding of brain physiology and pathophysiology and the effects of pharmacological interventions. To maximize the knowledge gained from these novel data types, pharmacometrics modelers may need to expand their toolbox to include additional mathematical and statistical frameworks. A session was held at the 10th annual American

   edit   deselect   + to AI

 

Conference on Pharmacometrics (ACoP10) to highlight several recent advancements in quantitative and systems neuroscience. In this mini-review, we provide a brief overview of technological and methodological advancements in the neuroscience therapeutic area that were discussed during the session and how these can be leveraged with quantitative systems pharmacology modeling to enhance our understanding of neurological diseases. Microphysiological systems using human induced pluripotent stem cells (IPSCs), digital biomarkers, and large-scale imaging offer more clinically relevant experimental datasets, enhanced granularity, and a plethora of data to potentially improve the preclinical-to-clinical translation of therapeutics. Network neuroscience methodologies combined with quantitative systems models of neurodegenerative disease could help bridge the gap between cellular and molecular alterations and clinical end points through the integration of information on neural connectomics.

   edit   deselect   + to AI

 

Additional topics, such as the neuroimmune system, microbiome, single-cell transcriptomic technologies, and digital device biomarkers, are discussed in brief. Quantitative systems pharmacology in neuroscience Wiley Online Library C:\Users\SarahCatanese\Zotero\storage\SQAYFBQJ\Bloomingdale et al. - 2021 - Quantitative systems pharmacology in neuroscience.pdf; C:\Users\SarahCatanese\Zotero\storage\PI6WMMJN\psp4.html

   edit   deselect   + to AI

 

journalArticle 2021 Underhill, Suzanne M.; Hullihen, Patrick D.; Chen, Jingshan; Fenollar-Ferrer, Cristina; Rizzo, M. A.; Ingram, Susan L.; Amara, Susan G. Amphetamines signal through intracellular TAAR1 receptors coupled to Gα13 and GαS in discrete subcellular domains Molecular Psychiatry 10.1038/s41380-019-0469-2 https://www.nature.com/articles/s41380-019-0469-2 The extensive use of amphetamines to treat attention deficit hyperactivity disorders in children provides a compelling rationale for understanding the mechanisms of action of amphetamines and amphetamine-related drugs. We have previously shown that acute amphetamine (AMPH) regulates the trafficking of both dopamine and glutamate transporters in dopamine neurons by increasing activation of the small GTPase RhoA and of protein kinase A. Here we demonstrate that these downstream signaling events depend upon the direct activation of a trace amine-associated receptor, TAAR1, an intracellular G-protein coupled receptor (GPCR)

   edit   deselect   + to AI

 

that can be activated by amphetamines, trace amines, and biogenic amine metabolites. Using cell lines and mouse lines in which TAAR1 expression has been disrupted, we demonstrate that TAAR1 mediates the effects of AMPH on both RhoA and cAMP signaling. Inhibition of different Gα signaling pathways in cell lines and in vivo using small cell-permeable peptides confirms that the endogenous intracellular TAAR1 couples to G13 and to GS α-subunits to increase RhoA and PKA activity, respectively. Results from experiments with RhoA- and PKA-FRET sensors targeted to different subcellular compartments indicate that AMPH-elicited PKA activation occurs throughout the cell, whereas G13-mediated RhoA activation is concentrated near the endoplasmic reticulum. These observations define TAAR1 as an obligate intracellular target for amphetamines in dopamine neurons and support a model in which distinct pools of TAAR1 mediate the activation of signaling pathways in different compartments to regulate

   edit   deselect   + to AI

 

excitatory and dopaminergic neurotransmission. Mol Psychiatry www.nature.com C:\Users\SarahCatanese\Zotero\storage\I4WSRS7G\Underhill et al. - 2021 - Amphetamines signal through intracellular TAAR1 re.pdf; C:\Users\SarahCatanese\Zotero\storage\7FUJF3HL\s41380-019-0469-2.html Cell biology; Neuroscience

   edit   deselect   + to AI

 

journalArticle 2021 Heffernan, Michele L. R.; Herman, Lee W.; Brown, Scott; Jones, Philip G.; Shao, Liming; Hewitt, Michael C.; Campbell, John E.; Dedic, Nina; Hopkins, Seth C.; Koblan, Kenneth S.; Xie, Linghong Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia ACS Medicinal Chemistry Letters 10.1021/acsmedchemlett.1c00527 https://doi.org/10.1021/acsmedchemlett.1c00527 Ulotaront (SEP-363856) is a trace-amine associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity in Phase 3 clinical development, with FDA Breakthrough Therapy Designation, for the treatment of schizophrenia. TAAR1 is a G-protein-coupled receptor (GPCR) that is expressed in cortical, limbic, and midbrain monoaminergic regions. It is activated by endogenous trace amines, and is believed to play an important role in modulating dopaminergic, serotonergic, and glutamatergic circuitry. TAAR1 agonism data are reported herein for ulotaront and its analogues in comparison to endogenous TAAR1

   edit   deselect   + to AI

 

agonists. In addition, a human TAAR1 homology model was built around ulotaront to identify key interactions and attempt to better understand the scaffold-specific TAAR1 agonism structure–activity relationships. ACS Med. Chem. Lett. Ulotaront ACS Publications C:\Users\SarahCatanese\Zotero\storage\F65PY7HF\acsmedchemlett.html; C:\Users\SarahCatanese\Zotero\storage\TEE93XVX\Heffernan et al. - 2021 - Ulotaront A TAAR1 Agonist for the Treatment of Sc.pdf

   edit   deselect   + to AI

 

webpage Experimental schizophrenia drug could reduce long-neglected symptoms https://www.science.org/content/article/experimental-schizophrenia-drug-could-reduce-long-neglected-symptoms New compound targets different neural receptors than existing antipsychotic drugs do C:\Users\SarahCatanese\Zotero\storage\VDF63EI8\experimental-schizophrenia-drug-could-reduce-long-neglected-symptoms.html

   edit   deselect   + to AI

 

webpage 2022 Two large studies reveal genes and genome regions that influence schizophrenia risk Broad Institute https://www.broadinstitute.org/news/two-large-studies-reveal-genes-and-genome-regions-influence-schizophrenia-risk International collaborations analyze common and rare DNA variants in hundreds of thousands of people, further elucidating genetic roots of psychiatric disorder C:\Users\SarahCatanese\Zotero\storage\KHMQBCCG\two-large-studies-reveal-genes-and-genome-regions-influence-schizophrenia-risk.html

   edit   deselect   + to AI

 

webpage Results | SCHEMA browser https://schema.broadinstitute.org/results C:\Users\SarahCatanese\Zotero\storage\Y385B6ZF\results.html

   edit   deselect   + to AI

 

report 2020 Singh, Tarjinder; Neale, Benjamin M.; Daly, Mark J.; Consortium, on behalf of the Schizophrenia Exome Meta-Analysis (SCHEMA) Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia https://www.medrxiv.org/content/10.1101/2020.09.18.20192815v1 By meta-analyzing the whole-exomes of 24,248 cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in ten genes as conferring substantial risk for schizophrenia (odds ratios 3 - 50, P < 2.14 × 10-6), and 32 genes at a FDR < 5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure, and function of the synapse. The associations of NMDA receptor subunit GRIN2A and AMPA receptor subunit GRIA3 provide support for the dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We find significant evidence for an overlap of

   edit   deselect   + to AI

 

rare variant risk between schizophrenia, autism spectrum disorders (ASD), and severe neurodevelopmental disorders (DD/ID), supporting a neurodevelopmental etiology for schizophrenia. We show that protein-truncating variants in GRIN2A, TRIO, and CACNA1G confer risk for schizophrenia whereas specific missense mutations in these genes confer risk for DD/ID. Nevertheless, few of the strongly associated schizophrenia genes appear to confer risk for DD/ID. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk, suggesting that common and rare genetic risk factors at least partially converge on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, implying that more schizophrenia risk genes await discovery using this approach. medRxiv medRxiv C:\Users\SarahCatanese\Zotero\storage\TJMVNZEI\Singh et al. - 2020 -

   edit   deselect   + to AI

 

Exome sequencing identifies rare coding variants i.pdf; C:\Users\SarahCatanese\Zotero\storage\KDA8LCAL\2020.09.18.html

   edit   deselect   + to AI

 

journalArticle 2021 Lam, Max; Chen, Chia-Yen; Ge, Tian; Xia, Yan; Hill, David W.; Trampush, Joey W.; Yu, Jin; Knowles, Emma; Davies, Gail; Stahl, Eli A.; Huckins, Laura; Liewald, David C.; Djurovic, Srdjan; Melle, Ingrid; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J.; Steen, Vidar M.; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Giegling, Ina; Konte, Bettina; Hartmann, Annette M.; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E.; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Koltai, Deborah C.; Need, Anna C.; Cirulli, Elizabeth T.; Voineskos, Aristotle N.; Stefanis, Nikos C.; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Smyrnis, Nikolaos; Bilder, Robert M.; Freimer, Nelson B.; Cannon, Tyrone D.; London, Edythe; Poldrack, Russell A.; Sabb, Fred W.; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A.; Dickinson, Dwight; Straub, Richard E.; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill,

   edit   deselect   + to AI

 

Michael; Hariri, Ahmad R.; Weinberger, Daniel R.; Pendleton, Neil; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C.; Andreassen, Ole A.; Deary, Ian J.; Glahn, David C.; Huang, Hailiang; Liu, Chunyu; Malhotra, Anil K.; Lencz, Todd Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 10.1038/s41386-021-01023-4 https://escholarship.org/uc/item/338966jd Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze

   edit   deselect   + to AI

 

results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. escholarship.org C:\Users\SarahCatanese\Zotero\storage\Q2E6EMTL\Lam et al. - 2021 - Identifying nootropic drug targets via large-scale.pdf;

   edit   deselect   + to AI

 

C:\Users\SarahCatanese\Zotero\storage\YQD3G3HT\338966jd.html

   edit   deselect   + to AI

 

journalArticle 2022 Barron, Daniel S.; Friedman, Richard A. The doors of precision: Reenergizing psychiatric drug development with psychedelics and open access computational tools Science Advances 10.1126/sciadv.abp8283 https://www.science.org/doi/10.1126/sciadv.abp8283 Psychedelics paired with new applications of computational tools might help bypass the imprecision of psychiatric diagnosis and connect measures of behavior to specific physiologic targets. Sci. Adv. The doors of precision DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\JULJWLHX\Barron and Friedman - 2022 - The doors of precision Reenergizing psychiatric d.pdf

   edit   deselect   + to AI

 

journalArticle 2021 Mejia-Gutierrez, Melissa; Vásquez-Paz, Bryan D.; Fierro, Leonardo; Maza, Julio R. In Silico Repositioning of Dopamine Modulators with Possible Application to Schizophrenia: Pharmacophore Mapping, Molecular Docking and Molecular Dynamics Analysis ACS Omega 10.1021/acsomega.0c05984 https://doi.org/10.1021/acsomega.0c05984 We have performed theoretical calculations with 70 drugs that have been considered in 231 clinical trials as possible candidates to repurpose drugs for schizophrenia based on their interactions with the dopaminergic system. A hypothesis of shared pharmacophore features was formulated to support our calculations. To do so, we have used the crystal structure of the D2-like dopamine receptor in complex with risperidone, eticlopride, and nemonapride. Linagliptin, citalopram, flunarizine, sildenafil, minocycline, and duloxetine were the drugs that best fit with our model. Molecular docking calculations, molecular dynamics outcomes, blood-brain barrier

   edit   deselect   + to AI

 

penetration, and human intestinal absorption were studied and compared with the results. From the six drugs selected in the shared pharmacophore features input, flunarizine showed the best docking score with D2, D3, and D4 dopamine receptors and had high stability during molecular dynamics simulations. Flunarizine is a frequently used medication to treat migraines and vertigo. However, its antipsychotic properties have been previously hypothesized, particularly because of its possible ability to block the D2 dopamine receptors. In Silico Repositioning of Dopamine Modulators with Possible Application to Schizophrenia ACS Publications C:\Users\SarahCatanese\Zotero\storage\MST7WW94\Mejia-Gutierrez et al. - 2021 - In Silico Repositioning of Dopamine Modulators wit.pdf

   edit   deselect   + to AI

 

journalArticle 2022 Lago, Santiago G.; Bahn, Sabine The druggable schizophrenia genome: from repurposing opportunities to unexplored drug targets npj Genomic Medicine 10.1038/s41525-022-00290-4 https://www.nature.com/articles/s41525-022-00290-4 There have been no new drugs for the treatment of schizophrenia in several decades and treatment resistance represents a major unmet clinical need. The drugs that exist are based on serendipitous clinical observations rather than an evidence-based understanding of disease pathophysiology. In the present review, we address these bottlenecks by integrating common, rare, and expression-related schizophrenia risk genes with knowledge of the druggability of the human genome as a whole. We highlight novel drug repurposing opportunities, clinical trial candidates which are supported by genetic evidence, and unexplored therapeutic opportunities in the lesser-known regions of the schizophrenia genome. By identifying translational gaps and opportunities

   edit   deselect   + to AI

 

across the schizophrenia disease space, we discuss a framework for translating increasingly well-powered genetic association studies into personalized treatments for schizophrenia and initiating the vital task of characterizing clinically relevant drug targets in underexplored regions of the human genome. npj Genom. Med. The druggable schizophrenia genome www.nature.com C:\Users\SarahCatanese\Zotero\storage\LXIP5VBU\Lago and Bahn - 2022 - The druggable schizophrenia genome from repurposi.pdf; C:\Users\SarahCatanese\Zotero\storage\3X998UB3\s41525-022-00290-4.html Schizophrenia; Genome; Pharmaceutics; Target identification

   edit   deselect   + to AI

 

journalArticle 2021 Shukla, Rammohan; Henkel, Nicholas D.; Alganem, Khaled; Hamoud, Abdul-rizaq; Reigle, James; Alnafisah, Rawan S.; Eby, Hunter M.; Imami, Ali S.; Creeden, Justin F; Miruzzi, Scott A.; Meller, Jaroslaw; Mccullumsmith, Robert E. Signature-based approaches for informed drug repurposing: targeting CNS disorders Neuropsychopharmacology 10.1038/s41386-020-0752-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688959/ CNS disorders, and in particular psychiatric illnesses, lack definitive disease-altering therapeutics. The limited understanding of the mechanisms driving these illnesses with the slow pace and high cost of drug development exacerbates this issue. For these reasons, drug repurposing – both a less expensive and time-efficient practice compared to de novo drug development – has been a promising strategy to overcome the paucity of treatments available for these debilitating disorders. While empirical drug-repurposing has been a routine practice in clinical

   edit   deselect   + to AI

 

psychiatry, innovative, informed, and cost-effective repurposing efforts using big data (“omics”) have been designed to characterize drugs by structural and transcriptomic signatures. These strategies, in conjunction with ontological integration, provide an important opportunity to address knowledge-based challenges associated with drug development for CNS disorders. In this review, we discuss various signature-based in silico approaches to drug repurposing, its integration with multiple omics platforms, and how this data can be used for clinically relevant, evidence-based drug repurposing. These tools provide an exciting translational avenue to merge omics-based drug discovery platforms with patient-specific disease signatures, ultimately facilitating the identification of new therapies for numerous psychiatric disorders. Neuropsychopharmacology Signature-based approaches for informed drug repurposing PubMed Central C:\Users\SarahCatanese\Zotero\storage\XV6HUGYC\Shukla et al. -

   edit   deselect   + to AI

 

2021 - Signature-based approaches for informed drug repur.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688959/

   edit   deselect   + to AI

 

journalArticle 2022 Barron, Daniel S.; Friedman, Richard A. The doors of precision: Reenergizing psychiatric drug development with psychedelics and open access computational tools Science Advances 10.1126/sciadv.abp8283 https://www.science.org/doi/10.1126/sciadv.abp8283 Psychedelics paired with new applications of computational tools might help bypass the imprecision of psychiatric diagnosis and connect measures of behavior to specific physiologic targets. Sci. Adv. The doors of precision DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\WW24JWLI\Barron and Friedman - 2022 - The doors of precision Reenergizing psychiatric d.pdf

   edit   deselect   + to AI

 

journalArticle 2019 Marder, Stephen R.; Cannon, Tyrone D. Schizophrenia New England Journal of Medicine 10.1056/NEJMra1808803 http://www.nejm.org/doi/10.1056/NEJMra1808803 N Engl J Med DOI.org (Crossref)

   edit   deselect   + to AI

 

journalArticle 2016 Estes, Myka L.; McAllister, A. Kimberley Maternal immune activation: Implications for neuropsychiatric disorders Science 10.1126/science.aag3194 https://www.science.org/doi/10.1126/science.aag3194 Epidemiological evidence implicates maternal infection as a risk factor for autism spectrum disorder and schizophrenia. Animal models corroborate this link and demonstrate that maternal immune activation (MIA) alone is sufficient to impart lifelong neuropathology and altered behaviors in offspring. This Review describes common principles revealed by these models, highlighting recent findings that strengthen their relevance for schizophrenia and autism and are starting to reveal the molecular mechanisms underlying the effects of MIA on offspring. The role of MIA as a primer for a much wider range of psychiatric and neurologic disorders is also discussed. Finally, the need for more research in this nascent field and the implications for identifying and developing new

   edit   deselect   + to AI

 

treatments for individuals at heightened risk for neuroimmune disorders are considered. Science Maternal immune activation DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\FEVAXBM2\Estes and McAllister - 2016 - Maternal immune activation Implications for neuro.pdf

   edit   deselect   + to AI

 

webpage Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia | bioRxiv https://www.biorxiv.org/content/10.1101/2022.03.07.483231v1 C:\Users\SarahCatanese\Zotero\storage\FRIVPGKJ\2022.03.07.html

   edit   deselect   + to AI

 

journalArticle 2021 Shukla, Rammohan; Henkel, Nicholas D.; Alganem, Khaled; Hamoud, Abdul-rizaq; Reigle, James; Alnafisah, Rawan S.; Eby, Hunter M.; Imami, Ali S.; Creeden, Justin F; Miruzzi, Scott A.; Meller, Jaroslaw; Mccullumsmith, Robert E. Signature-based approaches for informed drug repurposing: targeting CNS disorders Neuropsychopharmacology 10.1038/s41386-020-0752-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688959/ CNS disorders, and in particular psychiatric illnesses, lack definitive disease-altering therapeutics. The limited understanding of the mechanisms driving these illnesses with the slow pace and high cost of drug development exacerbates this issue. For these reasons, drug repurposing – both a less expensive and time-efficient practice compared to de novo drug development – has been a promising strategy to overcome the paucity of treatments available for these debilitating disorders. While empirical drug-repurposing has been a routine practice in clinical

   edit   deselect   + to AI

 

psychiatry, innovative, informed, and cost-effective repurposing efforts using big data (“omics”) have been designed to characterize drugs by structural and transcriptomic signatures. These strategies, in conjunction with ontological integration, provide an important opportunity to address knowledge-based challenges associated with drug development for CNS disorders. In this review, we discuss various signature-based in silico approaches to drug repurposing, its integration with multiple omics platforms, and how this data can be used for clinically relevant, evidence-based drug repurposing. These tools provide an exciting translational avenue to merge omics-based drug discovery platforms with patient-specific disease signatures, ultimately facilitating the identification of new therapies for numerous psychiatric disorders. Neuropsychopharmacology Signature-based approaches for informed drug repurposing PubMed Central C:\Users\SarahCatanese\Zotero\storage\6HA4P3T8\Shukla et al. -

   edit   deselect   + to AI

 

2021 - Signature-based approaches for informed drug repur.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688959/

   edit   deselect   + to AI

 

bookSection 2022 Talevi, Alan; Bellera, Carolina L. Drug Discovery Paradigms: Phenotypic-Based Drug Discovery Drug Target Selection and Validation 978-3-030-95895-4 https://doi.org/10.1007/978-3-030-95895-4_2 A drug discovery and development project typically starts with the identification of novel active scaffolds, i.e., core chemical structures with a desired biological effect. Beyond serendipitous discoveries and findings based on ethnopharmacology/traditional medicine, drug discovery in the modern age has been guided by two fundamental screening philosophies (implemented whether through in silico, in vitro or less often, in vivo approximations). Occasionally, novel chemotypes can be designed de novo by searching for complementary features to a binding site in a predefined drug target. Historically, systematic screening for new active compounds comprised phenotypic screening assays (e.g., against a collection of microorganisms, animal models of disease, or cellular models). Later,

   edit   deselect   + to AI

 

the interest of the pharmaceutical companies experienced a substantial shift toward target-focused approximations in which exquisitely selective compounds were sought, usually through high-throughput screening. There, the test compounds were typically confronted with some biological entity, usually a protein, to identify those which could modulate such biomolecule. Nevertheless, as target-focused approximation failed to deliver the expectations, especially when pursuing therapies for complex disorders, renewed interest in phenotypic screening was observed in the pharmaceutical community, supported by a network pharmacology paradigm, high-content screening, small animal models, and organoids and other advanced cell culture platforms. Drug Discovery Paradigms Springer International Publishing Springer Link Drug discovery; High-content analysis; High-content screening (HCS); High-throughput screening; Hit identification; Phenotypic screening; Target deconvolution; Target-focused

   edit   deselect   + to AI

 

approximations

   edit   deselect   + to AI

 

report 2022 Koch, Elise; Kauppi, Karolina; Chen, Chi-Hua Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia http://biorxiv.org/lookup/doi/10.1101/2022.03.07.483231 In the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After

   edit   deselect   + to AI

 

excluding drugs contraindicated in schizophrenia, we identified eight drug candidates, most of which have anti-inflammatory and neuroprotective effects. Due to gene expression differences in male and female patients, four of those drugs were also selected in our male-specific analyses, and the other four in the female-specific analyses. Based on our bioinformatics analyses of disease genetics, we suggest eight candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options. Genetics DOI.org (Crossref) C:\Users\SarahCatanese\Zotero\storage\7SKG6VKU\Koch et al. - 2022 - Candidates for Drug Repurposing to Address the Cog.pdf

   edit   deselect   + to AI

 

journalArticle 2021 Zanin, Massimiliano; Aitya, Nadim A.A.; Basilio, José; Baumbach, Jan; Benis, Arriel; Behera, Chandan K.; Bucholc, Magda; Castiglione, Filippo; Chouvarda, Ioanna; Comte, Blandine; Dao, Tien-Tuan; Ding, Xuemei; Pujos-Guillot, Estelle; Filipovic, Nenad; Finn, David P.; Glass, David H.; Harel, Nissim; Iesmantas, Tomas; Ivanoska, Ilinka; Joshi, Alok; Boudjeltia, Karim Zouaoui; Kaoui, Badr; Kaur, Daman; Maguire, Liam P.; McClean, Paula L.; McCombe, Niamh; de Miranda, João Luís; Moisescu, Mihnea Alexandru; Pappalardo, Francesco; Polster, Annikka; Prasad, Girijesh; Rozman, Damjana; Sacala, Ioan; Sanchez-Bornot, Jose M.; Schmid, Johannes A.; Sharp, Trevor; Solé-Casals, Jordi; Spiwok, Vojtěch; Spyrou, George M.; Stalidzans, Egils; Stres, Blaž; Sustersic, Tijana; Symeonidis, Ioannis; Tieri, Paolo; Todd, Stephen; Van Steen, Kristel; Veneva, Milena; Wang, Da-Hui; Wang, Haiying; Wang, Hui; Watterson, Steven; Wong-Lin, KongFatt; Yang, Su; Zou, Xin; Schmidt, Harald H.H.W. An Early

   edit   deselect   + to AI

 

Stage Researcher's Primer on Systems Medicine Terminology Network and Systems Medicine 10.1089/nsm.2020.0003 https://www.liebertpub.com/doi/10.1089/nsm.2020.0003 Background: Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. Methods: In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of

   edit   deselect   + to AI

 

applications, and lists of relevant references. Results: This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term, where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic. liebertpub.com (Atypon) C:\Users\SarahCatanese\Zotero\storage\ND4V4A5X\Zanin et al. - 2021 - An Early Stage Researcher's Primer on Systems Medi.pdf multiscale data science; multiscale modeling; systems medicine

   edit   deselect   + to AI

 

journalArticle 2021 Lam, Max; Chen, Chia-Yen; Ge, Tian; Xia, Yan; Hill, David W.; Trampush, Joey W.; Yu, Jin; Knowles, Emma; Davies, Gail; Stahl, Eli A.; Huckins, Laura; Liewald, David C.; Djurovic, Srdjan; Melle, Ingrid; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J.; Steen, Vidar M.; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Giegling, Ina; Konte, Bettina; Hartmann, Annette M.; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E.; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Koltai, Deborah C.; Need, Anna C.; Cirulli, Elizabeth T.; Voineskos, Aristotle N.; Stefanis, Nikos C.; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Smyrnis, Nikolaos; Bilder, Robert M.; Freimer, Nelson B.; Cannon, Tyrone D.; London, Edythe; Poldrack, Russell A.; Sabb, Fred W.; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A.; Dickinson, Dwight; Straub, Richard E.; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill,

   edit   deselect   + to AI

 

Michael; Hariri, Ahmad R.; Weinberger, Daniel R.; Pendleton, Neil; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C.; Andreassen, Ole A.; Deary, Ian J.; Glahn, David C.; Huang, Hailiang; Liu, Chunyu; Malhotra, Anil K.; Lencz, Todd Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 10.1038/s41386-021-01023-4 https://escholarship.org/uc/item/338966jd Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze

   edit   deselect   + to AI

 

results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. escholarship.org C:\Users\SarahCatanese\Zotero\storage\9QMTIT9S\Lam et al. - 2021 - Identifying nootropic drug targets via large-scale.pdf;

   edit   deselect   + to AI

 

C:\Users\SarahCatanese\Zotero\storage\I8VG7KRU\338966jd.html

   edit   deselect   + to AI

 

journalArticle 2020 Rutigliano, Grazia; Zucchi, Riccardo Molecular Variants in Human Trace Amine-Associated Receptors and Their Implications in Mental and Metabolic Disorders Cellular and Molecular Neurobiology 10.1007/s10571-019-00743-y https://doi.org/10.1007/s10571-019-00743-y We provide a comprehensive review of the available evidence on the pathophysiological implications of genetic variants in the human trace amine-associated receptor (TAAR) superfamily. Genes coding for trace amine-associated receptors (taars) represent a multigene family of G-protein-coupled receptors, clustered to a small genomic region of 108 kb located in chromosome 6q23, which has been consistently identified by linkage analyses as a susceptibility locus for schizophrenia and affective disorders. Most TAARs are expressed in brain areas involved in emotions, reward and cognition. TAARs are activated by endogenous trace amines and thyronamines, and evidence for a modulatory action on other monaminergic

   edit   deselect   + to AI

 

systems has been reported. Therefore, linkage analyses were followed by fine mapping association studies in schizophrenia and affective disorders. However, none of these reports has received sufficient universal replication, so their status remains uncertain. Single nucleotide polymorphisms in taars have emerged as susceptibility loci from genome-wide association studies investigating migraine and brain development, but none of the detected variants reached the threshold for genome-wide significance. In the last decade, technological advances enabled single-gene or whole-exome sequencing, thus allowing the detection of rare genetic variants, which may have a greater impact on the risk of complex disorders. Using these approaches, several taars (especially taar1) variants have been detected in patients with mental and metabolic disorders, and in some cases, defective receptor function has been demonstrated in vitro. Finally, with the use of transcriptomic and peptidomic techniques,

   edit   deselect   + to AI

 

dysregulations of TAARs (especially TAAR6) have been identified in brain disorders characterized by cognitive impairment. Cell Mol Neurobiol Springer Link C:\Users\SarahCatanese\Zotero\storage\WBDH8DBY\Rutigliano and Zucchi - 2020 - Molecular Variants in Human Trace Amine-Associated.pdf Schizophrenia; Bipolar disorder; Genetics; Single nucletide polymorphism; Trace amine-associated receptors

   edit   deselect   + to AI

 

journalArticle 2022 Xiao, Guangqing; Chen, Yu-Luan; Dedic, Nina; Xie, Linghong; Koblan, Kenneth S.; Galluppi, Gerald R. In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HT1A Receptor Agonist for the Treatment of Schizophrenia Pharmaceutical Research 10.1007/s11095-022-03267-1 PURPOSE: Ulotaront (SEP-363856) is a TAAR1 agonist with 5-HT1A agonist activity currently in clinical development for the treatment of schizophrenia. The objectives of the current study were to characterize the in vitro ADME properties, preclinical PK, and to evaluate the DDI potential of ulotaront and its major metabolite SEP-383103. METHODS: Solubility, permeability, plasma protein binding, CYP inhibition and induction, transporter inhibition and uptake studies were conducted in vitro. Phenotyping studies were conducted using recombinant human CYPs and FMOs, human liver microsomes and human liver homogenates. Preclinical plasma and brain pharmacokinetics were determined after a single

   edit   deselect   + to AI

 

intraperitoneal, intravenous, and oral administration of ulotaront. RESULTS: Ulotaront is a compound of high solubility, high permeability, and low binding to plasma proteins. Ulotaront metabolism is mediated via both NADPH-dependent and NADPH-independent pathways, with CYP2D6 as the major metabolizing enzyme. Ulotaront is an inducer of CYP2B6, and an inhibitor of CYP2D6, OCT1 and OCT2, while SEP-383103 is neither a CYP inducer nor a potent inhibitor of CYPs and human transporters. Ulotaront exhibits rapid absorption, greater than 70% bioavailability, approximately 3.5 L/kg volume of distribution, 1.5-4 h half-life, 12-43 ml/min/kg clearance, and good penetration across the blood-brain barrier in preclinical species. CONCLUSIONS: Ulotaront has been designated as a BCS1 compound by US FDA. The ability of ulotaront to penetrate the blood-brain barrier for CNS targeting has been demonstrated in mice and rats. The potential for ulotaront and SEP-383103 to act as perpetrators of CYP and

   edit   deselect   + to AI

 

transporter-mediated DDIs is predicted to be remote. Pharm Res PubMed http://www.ncbi.nlm.nih.gov/pubmed/35484370 Schizophrenia; Pharmaceutical Preparations; Animals; blood–brain barrier; CYP2D6; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; drug-drug interactions; Mice; Microsomes, Liver; NADP; phenotyping; Rats; Receptor, Serotonin, 5-HT1A; TAAR1; ulotaront

   edit   deselect   + to AI

 

journalArticle 2016 Gilson, Michael K.; Liu, Tiqing; Baitaluk, Michael; Nicola, George; Hwang, Linda; Chong, Jenny BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology Nucleic Acids Research 10.1093/nar/gkv1072 BindingDB, www.bindingdb.org, is a publicly accessible database of experimental protein-small molecule interaction data. Its collection of over a million data entries derives primarily from scientific articles and, increasingly, US patents. BindingDB provides many ways to browse and search for data of interest, including an advanced search tool, which can cross searches of multiple query types, including text, chemical structure, protein sequence and numerical affinities. The PDB and PubMed provide links to data in BindingDB, and vice versa; and BindingDB provides links to pathway information, the ZINC catalog of available compounds, and other resources. The BindingDB website offers specialized tools that take

   edit   deselect   + to AI

 

advantage of its large data collection, including ones to generate hypotheses for the protein targets bound by a bioactive compound, and for the compounds bound by a new protein of known sequence; and virtual compound screening by maximal chemical similarity, binary kernel discrimination, and support vector machine methods. Specialized data sets are also available, such as binding data for hundreds of congeneric series of ligands, drawn from BindingDB and organized for use in validating drug design methods. BindingDB offers several forms of programmatic access, and comes with extensive background material and documentation. Here, we provide the first update of BindingDB since 2007, focusing on new and unique features and highlighting directions of importance to the field as a whole. Nucleic Acids Res BindingDB in 2015 PubMed C:\Users\SarahCatanese\Zotero\storage\JX3KQHGJ\Gilson et al. - 2016 - BindingDB in 2015 A public database for medicinal.pdf;

   edit   deselect   + to AI

 

http://www.ncbi.nlm.nih.gov/pubmed/26481362 Pharmaceutical Preparations; Software; Databases, Pharmaceutical; Drug Design; Internet; Ligands; Patents as Topic; Protein Binding; Protein Folding; Proteins; Systems Biology

   edit   deselect   + to AI

 

journalArticle 2020 Xu, Zhengrong; Li, Qian TAAR Agonists Cellular and Molecular Neurobiology 10.1007/s10571-019-00774-5 Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors (GPCRs) that are evolutionarily conserved in vertebrates. The first discovered TAAR1 is mainly expressed in the brain, and is able to detect low abundant trace amines. TAAR1 is also activated by several synthetic compounds and psychostimulant drugs like amphetamine. Activation of TAAR1 by specific agonists can regulate the classical monoaminergic systems in the brain. Further studies have revealed that other TAAR family members are highly expressed in the olfactory system which are termed olfactory TAARs. In vertebrates, olfactory TAARs can specifically recognize volatile or water-soluble amines. Some of these TAAR agonists are produced by decarboxylation of amino acids. In addition, some TAAR agonists are ethological odors that mediate animal innate behaviors. In this study, we

   edit   deselect   + to AI

 

provide a comprehensive review of TAAR agonists, including their structures, biosynthesis pathways, and functions. Cell Mol Neurobiol PubMed http://www.ncbi.nlm.nih.gov/pubmed/31848873 Humans; Animals; Agonist; Biogenic Amines; Central Nervous System Stimulants; G protein-coupled receptor (GPCR); Olfactory receptor; Receptors, G-Protein-Coupled; Signal Transduction; Trace amine-associated receptor (TAAR); Trace amines; Volatile amines

   edit   deselect   + to AI

 

journalArticle 2019 Corlett, Philip R.; Horga, Guillermo; Fletcher, Paul C.; Alderson-Day, Ben; Schmack, Katharina; Powers, Albert R. Hallucinations and Strong Priors Trends in Cognitive Sciences 10.1016/j.tics.2018.12.001 Hallucinations, perceptions in the absence of objectively identifiable stimuli, illustrate the constructive nature of perception. Here, we highlight the role of prior beliefs as a critical elicitor of hallucinations. Recent empirical work from independent laboratories shows strong, overly precise priors can engender hallucinations in healthy subjects and that individuals who hallucinate in the real world are more susceptible to these laboratory phenomena. We consider these observations in light of work demonstrating apparently weak, or imprecise, priors in psychosis. Appreciating the interactions within and between hierarchies of inference can reconcile this apparent disconnect. Data from neural networks, human behavior, and neuroimaging support this contention.

   edit   deselect   + to AI

 

This work underlines the continuum from normal to aberrant perception, encouraging a more empathic approach to clinical hallucinations. Trends Cogn Sci PubMed C:\Users\SarahCatanese\Zotero\storage\U4TUGXF9\Corlett et al. - 2019 - Hallucinations and Strong Priors.pdf; http://www.ncbi.nlm.nih.gov/pubmed/30583945 Illusions; psychosis; Humans; auditory verbal hallucinations; hallucinations; predictive coding; prior beliefs; Hallucinations; Nerve Net; Speech Perception

   edit   deselect   + to AI

 

journalArticle 2022 Nair, Pramod C.; Chalker, Justin M.; McKinnon, Ross A.; Langmead, Christopher J; Gregory, Karen J.; Bastiampillai, Tarun Trace Amine-Associated Receptor 1 (TAAR1): Molecular and Clinical Insights for the Treatment of Schizophrenia and Related Comorbidities ACS Pharmacology & Translational Science 10.1021/acsptsci.2c00016 https://doi.org/10.1021/acsptsci.2c00016 Schizophrenia is a complex and severe mental illness. Current treatments for schizophrenia typically modulate dopaminergic neurotransmission by D2-receptor blockade. While reducing positive symptoms of schizophrenia, current antipsychotic drugs have little clinical effect on negative symptoms and cognitive impairments. For the last few decades, discovery efforts have sought nondopaminergic compounds with the aim to effectively treat the broad symptoms of schizophrenia. In this viewpoint, we provide an overview on trace-amine associated receptor-1 (TAAR1), which presents a clinically validated

   edit   deselect   + to AI

 

nondopaminergic target for treating schizophrenia and related disorders, with significantly less overall side-effect burden. TAAR1 agonists may also be specifically beneficial for the substance abuse comorbidity and metabolic syndrome that is often present in patients with schizophrenia. ACS Pharmacol. Transl. Sci. Trace Amine-Associated Receptor 1 (TAAR1) ACS Publications C:\Users\SarahCatanese\Zotero\storage\9TB4YCLZ\acsptsci.html; C:\Users\SarahCatanese\Zotero\storage\ZYLW5XQT\Nair et al. - 2022 - Trace Amine-Associated Receptor 1 (TAAR1) Molecul.pdf

   edit   deselect   + to AI

 

webpage Redefining the standard of care for brain disorders | MapLight Therapeutics MapLight https://maplightrx.com/ Targeted treatment for Autism Spectrum Disorder, Parkinson’s Disease and Schizophrenia. C:\Users\SarahCatanese\Zotero\storage\Y8FRT6CC\maplightrx.com.html

   edit   deselect   + to AI

 

journalArticle Bugda Gwilt, Katlynn; González, Dulce Pamela; Olliffe, Neva; Oller, Haley; Hoffing, Rachel; Puzan, Marissa; El Aidy, Sahar; Miller, Gregory M. Actions of Trace Amines in the Brain-Gut-Microbiome Axis via Trace Amine-Associated Receptor-1 (TAAR1) Cellular and Molecular Neurobiology 10.1007/s10571-019-00772-7 Trace amines and their primary receptor, Trace Amine-Associated Receptor-1 (TAAR1) are widely studied for their involvement in the pathogenesis of neuropsychiatric disorders despite being found in the gastrointestinal tract at physiological levels. With the emergence of the “brain-gut-microbiome axis,” we take the opportunity to review what is known about trace amines in the brain, the defined sources of trace amines in the gut, and emerging understandings on the levels of trace amines in various gastrointestinal disorders. Similarly, we discuss localization of TAAR1 expression in the gut, novel findings that TAAR1 may be implicated in inflammatory bowel diseases,

   edit   deselect   + to AI

 

and the reported comorbidities of neuropsychiatric disorders and gastrointestinal disorders. With the emergence of TAAR1 specific compounds as next-generation therapeutics for schizophrenia (Roche) and Parkinson’s related psychoses (Sunovion), we hypothesize a therapeutic benefit of these compounds in clinical trials in the brain-gut-microbiome axis, as well as a potential for thoughtful manipulation of the brain-gut-microbiome axis to modulate symptoms of neuropsychiatric disease. Dimensions <p>https://pure.rug.nl/ws/files/111443102/BugdaGwilt2019_Article_ActionsOfTraceAminesInTheBrain.pdf&lt;/p&gt; C:\Users\SarahCatanese\Zotero\storage\3Y2SQ7WG\Bugda Gwilt et al. - Actions of Trace Amines in the Brain-Gut-Microbiom.pdf

   edit   deselect   + to AI

 

journalArticle 2021 Zanin, Massimiliano; Aitya, Nadim A.A.; Basilio, José; Baumbach, Jan; Benis, Arriel; Behera, Chandan K.; Bucholc, Magda; Castiglione, Filippo; Chouvarda, Ioanna; Comte, Blandine; Dao, Tien-Tuan; Ding, Xuemei; Pujos-Guillot, Estelle; Filipovic, Nenad; Finn, David P.; Glass, David H.; Harel, Nissim; Iesmantas, Tomas; Ivanoska, Ilinka; Joshi, Alok; Boudjeltia, Karim Zouaoui; Kaoui, Badr; Kaur, Daman; Maguire, Liam P.; McClean, Paula L.; McCombe, Niamh; de Miranda, João Luís; Moisescu, Mihnea Alexandru; Pappalardo, Francesco; Polster, Annikka; Prasad, Girijesh; Rozman, Damjana; Sacala, Ioan; Sanchez-Bornot, Jose M.; Schmid, Johannes A.; Sharp, Trevor; Solé-Casals, Jordi; Spiwok, Vojtěch; Spyrou, George M.; Stalidzans, Egils; Stres, Blaž; Sustersic, Tijana; Symeonidis, Ioannis; Tieri, Paolo; Todd, Stephen; Van Steen, Kristel; Veneva, Milena; Wang, Da-Hui; Wang, Haiying; Wang, Hui; Watterson, Steven; Wong-Lin, KongFatt; Yang, Su; Zou, Xin; Schmidt, Harald H.H.W. An Early

   edit   deselect   + to AI

 

Stage Researcher's Primer on Systems Medicine Terminology Network and Systems Medicine 10.1089/nsm.2020.0003 https://www.liebertpub.com/doi/10.1089/nsm.2020.0003 Background: Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. Methods: In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of

   edit   deselect   + to AI

 

applications, and lists of relevant references. Results: This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term, where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic. liebertpub.com (Atypon) C:\Users\SarahCatanese\Zotero\storage\V6AY7M6H\Zanin et al. - 2021 - An Early Stage Researcher's Primer on Systems Medi.pdf multiscale data science; multiscale modeling; systems medicine

   edit   deselect   + to AI

 

journalArticle 2021 Gomes, Felipe V.; Grace, Anthony A. Beyond Dopamine Receptor Antagonism: New Targets for Schizophrenia Treatment and Prevention International Journal of Molecular Sciences 10.3390/ijms22094467 Treatment of schizophrenia (SCZ) historically relies on the use of antipsychotic drugs to treat psychosis, with all of the currently available antipsychotics acting through the antagonism of dopamine D2 receptors. Although antipsychotics reduce psychotic symptoms in many patients, they induce numerous undesirable effects and are not effective against negative and cognitive symptoms. These highlight the need to develop new drugs to treat SCZ. An advanced understanding of the circuitry of SCZ has pointed to pathological origins in the excitation/inhibition balance in regions such as the hippocampus, and restoring function in this region, particularly as a means to compensate for parvalbumin (PV) interneuron loss and resultant hippocampal hyperactivity, may be a more

   edit   deselect   + to AI

 

efficacious approach to relieve a broad range of SCZ symptoms. Other targets, such as cholinergic receptors and the trace amine-associated receptor 1 (TAAR1), have also shown some promise for the treatment of SCZ. Importantly, assessing efficacy of novel compounds must take into consideration treatment history of the patient, as preclinical studies suggest prior antipsychotic treatment may interfere with the efficacy of these novel agents. However, while novel therapeutic targets may be more effective in treating SCZ, a more effective approach would be to prevent the transition to SCZ in susceptible individuals. A focus on stress, which has been shown to be a predisposing factor in risk for SCZ, is a possible avenue that has shown promise in preclinical studies. Therefore, therapeutic approaches based on our current understanding of the circuitry of SCZ and its etiology are likely to enable development of more effective therapeutic interventions for this complex disorder. Int J Mol

   edit   deselect   + to AI

 

Sci Beyond Dopamine Receptor Antagonism PubMed C:\Users\SarahCatanese\Zotero\storage\A5TEMVIK\Gomes and Grace - 2021 - Beyond Dopamine Receptor Antagonism New Targets f.pdf; http://www.ncbi.nlm.nih.gov/pubmed/33922888 antipsychotics; dopamine; Schizophrenia; psychosis; Humans; Antipsychotic Agents; glutamate; Animals; Receptors, G-Protein-Coupled; D-Amino-Acid Oxidase; Dopamine Antagonists; gamma-Aminobutyric Acid; Glutamic Acid; hippocampus; Molecular Targeted Therapy; parvalbumin; Receptors, Cholinergic; Sodium Benzoate; stress

   edit   deselect   + to AI

 

journalArticle 2021 Alnefeesi, Yazen; Tamura, Jocelyn K.; Lui, Leanna M. W.; Jawad, Muhammad Youshay; Ceban, Felicia; Ling, Susan; Nasri, Flora; Rosenblat, Joshua D.; McIntyre, Roger S. Trace amine-associated receptor 1 (TAAR1): Potential application in mood disorders: A systematic review Neuroscience & Biobehavioral Reviews 10.1016/j.neubiorev.2021.09.020 https://www.sciencedirect.com/science/article/pii/S0149763421004024 There is a need for innovation with respect to therapeutics in psychiatry. Available evidence indicates that the trace amine-associated receptor 1 (TAAR1) agonist SEP-363856 is promising, as it improves measures of cognitive and reward function in schizophrenia. Hedonic and cognitive impairments are transdiagnostic and constitute major burdens in mood disorders. Herein, we systematically review the behavioural and genetic literature documenting the role of TAAR1 in reward and cognitive function, and propose a mechanistic model of TAAR1’s functions in the brain.

   edit   deselect   + to AI

 

Notably, TAAR1 activity confers antidepressant-like effects, enhances attention and response inhibition, and reduces compulsive reward seeking without impairing normal function. Further characterization of the responsible mechanisms suggests ion-homeostatic, metabolic, neurotrophic, and anti-inflammatory enhancements in the limbic system. Multiple lines of evidence establish the viability of TAAR1 as a biological target for the treatment of mood disorders. Furthermore, the evidence suggests a role for TAAR1 in reward and cognitive function, which is attributed to a cascade of events that are relevant to the cellular integrity and function of the central nervous system. Neuroscience & Biobehavioral Reviews Trace amine-associated receptor 1 (TAAR1) ScienceDirect C:\Users\SarahCatanese\Zotero\storage\S2B5IYCG\S0149763421004024.html Bipolar disorder; Depression; Arousal; Attention; Brain derived neurotrophic factor (BDNF); Cognitive control; Cognitive function; Mammalian target of

   edit   deselect   + to AI

 

rapamycin (mTOR); Medial prefrontal cortex (mPFC); Reward function; Trace amine-associated receptor 1 (TAAR1); Ventral tegmental area (VTA)

   edit   deselect   + to AI

 

journalArticle 2001 Borowsky, Beth; Adham, Nika; Jones, Kenneth A.; Raddatz, Rita; Artymyshyn, Roman; Ogozalek, Kristine L.; Durkin, Margaret M.; Lakhlani, Parul P.; Bonini, James A.; Pathirana, Sudam; Boyle, Noel; Pu, Xiaosui; Kouranova, Evguenia; Lichtblau, Harvey; Ochoa, F. Yulina; Branchek, Theresa A.; Gerald, Christophe Trace amines: Identification of a family of mammalian G protein-coupled receptors Proceedings of the National Academy of Sciences 10.1073/pnas.151105198 https://www.pnas.org/doi/full/10.1073/pnas.151105198 Trace amines pnas.org (Atypon) C:\Users\SarahCatanese\Zotero\storage\HFVBXSAQ\Borowsky et al. - 2001 - Trace amines Identification of a family of mammal.pdf

   edit   deselect   + to AI

 

journalArticle 2017 Mittal, Vijay A; Bernard, Jessica A; Northoff, Georg What Can Different Motor Circuits Tell Us About Psychosis? An RDoC Perspective Schizophrenia Bulletin 10.1093/schbul/sbx087 https://doi.org/10.1093/schbul/sbx087 Signs of motor dysfunction are evidenced across a range of psychiatric disorders including schizophrenia. Historically, these features have been neglected but emerging theoretical and methodological advancements have shed new light on the utility of considering movement abnormalities. Indeed, the National Institute of Mental Health Research Domain Criteria initiative has recently met to develop a Motor Systems Domain. This reflects a growing appreciation for the enhanced reliability and validity that can come along with evaluating disturbances relevant to psychiatric illnesses from multiple levels of analysis, and conceptualizing these domains with respect to the complexity of their role in a broader integrated system (ie, weighing contributions and

   edit   deselect   + to AI

 

interactions between the cognitive, affective, and motor domains). This article discusses motor behaviors and seeks to explain how research into basal ganglia, cerebellar, and cortico-motor circuit function/dysfunction, grounded in brain circuit-motor behavior relationships, can elucidate our understanding of pathophysiology, provide vital links to other key systems of interest, significantly improve identification and classification, and drive development of targeted individualized treatments. Schizophrenia Bulletin What Can Different Motor Circuits Tell Us About Psychosis? Silverchair C:\Users\SarahCatanese\Zotero\storage\F2RY2T5F\Mittal et al. - 2017 - What Can Different Motor Circuits Tell Us About Ps.pdf; C:\Users\SarahCatanese\Zotero\storage\GWRSWWJG\3924241.html

   edit   deselect   + to AI

 

journalArticle 2022 Spark, Daisy L.; Fornito, Alex; Langmead, Christopher J.; Stewart, Gregory D. Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics Translational Psychiatry 10.1038/s41398-022-01904-2 https://www.nature.com/articles/s41398-022-01904-2 Despite 50+ years of drug discovery, current antipsychotics have limited efficacy against negative and cognitive symptoms of schizophrenia, and are ineffective—with the exception of clozapine—against any symptom domain for patients who are treatment resistant. Novel therapeutics with diverse non-dopamine D2 receptor targets have been explored extensively in clinical trials, yet often fail due to a lack of efficacy despite showing promise in preclinical development. This lack of translation between preclinical and clinical efficacy suggests a systematic failure in current methods that determine efficacy in preclinical rodent models. In this review, we critically evaluate rodent

   edit   deselect   + to AI

 

models and behavioural tests used to determine preclinical efficacy, and look to clinical research to provide a roadmap for developing improved translational measures. We highlight the dependence of preclinical models and tests on dopamine-centric theories of dysfunction and how this has contributed towards a self-reinforcing loop away from clinically meaningful predictions of efficacy. We review recent clinical findings of distinct dopamine-mediated dysfunction of corticostriatal circuits in patients with treatment-resistant vs. non-treatment-resistant schizophrenia and suggest criteria for establishing rodent models to reflect such differences, with a focus on objective, translational measures. Finally, we review current schizophrenia drug discovery and propose a framework where preclinical models are validated against objective, clinically informed measures and preclinical tests of efficacy map onto those used clinically. Transl Psychiatry Beyond antipsychotics www.nature.com

   edit   deselect   + to AI

 

C:\Users\SarahCatanese\Zotero\storage\FB9MAFN5\Spark et al. - 2022 - Beyond antipsychotics a twenty-first century upda.pdf; C:\Users\SarahCatanese\Zotero\storage\GKSQB7CG\s41398-022-01904-2.html Molecular neuroscience; Predictive markers

   edit   deselect   + to AI

 

webpage Impact of GPCR Structures on Drug Discovery - ScienceDirect https://www.sciencedirect.com/science/article/pii/S0092867420302658#mmc4

   edit   deselect   + to AI

 

journalArticle 2021 Olson, David E. The Promise of Psychedelic Science ACS Pharmacology & Translational Science 10.1021/acsptsci.1c00071 https://doi.org/10.1021/acsptsci.1c00071 ACS Pharmacol. Transl. Sci. <p>doi: 10.1021/acsptsci.1c00071</p>

   edit   deselect   + to AI

 

journalArticle 2022 Arnovitz, Mitchell D.; Spitzberg, Andrew J.; Davani, Ashkhan J.; Vadhan, Nehal P.; Holland, Julie; Kane, John M.; Michaels, Timothy I. MDMA for the Treatment of Negative Symptoms in Schizophrenia Journal of Clinical Medicine 10.3390/jcm11123255 https://www.mdpi.com/2077-0383/11/12/3255 The profound economic burden of schizophrenia is due, in part, to the negative symptoms of the disease, which can severely limit daily functioning. There is much debate in the field regarding their measurement and classification and there are no FDA-approved treatments for negative symptoms despite an abundance of research. 3,4-Methylenedioxy methamphetamine (MDMA) is a schedule I substance that has emerged as a novel therapeutic given its ability to enhance social interactions, generate empathy, and induce a state of metaplasticity in the brain. This review provides a rationale for the use of MDMA in the treatment of negative symptoms by reviewing the literature on negative

   edit   deselect   + to AI

 

symptoms, their treatment, MDMA, and MDMA-assisted therapy. It reviews recent evidence that supports the safe and potentially effective use of MDMA to treat negative symptoms and concludes with considerations regarding safety and possible mechanisms of action. www.mdpi.com C:\Users\SarahCatanese\Zotero\storage\47PGR729\Arnovitz et al. - 2022 - MDMA for the Treatment of Negative Symptoms in Sch.pdf schizophrenia; psychosis; MDMA; negative symptoms; psychedelic-assisted therapy

   edit   deselect   + to AI

 

journalArticle 2022 Spark, Daisy L.; Fornito, Alex; Langmead, Christopher J.; Stewart, Gregory D. Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics Translational Psychiatry 10.1038/s41398-022-01904-2 https://www.nature.com/articles/s41398-022-01904-2 Despite 50+ years of drug discovery, current antipsychotics have limited efficacy against negative and cognitive symptoms of schizophrenia, and are ineffective—with the exception of clozapine—against any symptom domain for patients who are treatment resistant. Novel therapeutics with diverse non-dopamine D2 receptor targets have been explored extensively in clinical trials, yet often fail due to a lack of efficacy despite showing promise in preclinical development. This lack of translation between preclinical and clinical efficacy suggests a systematic failure in current methods that determine efficacy in preclinical rodent models. In this review, we critically evaluate rodent

   edit   deselect   + to AI

 

models and behavioural tests used to determine preclinical efficacy, and look to clinical research to provide a roadmap for developing improved translational measures. We highlight the dependence of preclinical models and tests on dopamine-centric theories of dysfunction and how this has contributed towards a self-reinforcing loop away from clinically meaningful predictions of efficacy. We review recent clinical findings of distinct dopamine-mediated dysfunction of corticostriatal circuits in patients with treatment-resistant vs. non-treatment-resistant schizophrenia and suggest criteria for establishing rodent models to reflect such differences, with a focus on objective, translational measures. Finally, we review current schizophrenia drug discovery and propose a framework where preclinical models are validated against objective, clinically informed measures and preclinical tests of efficacy map onto those used clinically. Transl Psychiatry Beyond antipsychotics www.nature.com

   edit   deselect   + to AI

 

C:\Users\SarahCatanese\Zotero\storage\GFAM6V6T\Spark et al. - 2022 - Beyond antipsychotics a twenty-first century upda.pdf; C:\Users\SarahCatanese\Zotero\storage\MCRN6YQE\s41398-022-01904-2.html Molecular neuroscience; Predictive markers

   edit   deselect   + to AI

 

webpage Inflammatory bowel disease-associated gene set projecte | Open-i https://openi.nlm.nih.gov/detailedresult?img=PMC4251289_fphar-05-00252-g003&amp;query=multiscale%20neuron&amp;it=xg&amp;req=4&amp;npos=52 C:\Users\SarahCatanese\Zotero\storage\ZZTDM6RW\detailedresult.html

   edit   deselect   + to AI

 

Finding new ways to repurpose existing drugs to treat schizophrenia by targeting different genes and system in the disease.

   edit   deselect   + to AI

 

Develop a drug that specifically targets the symptoms of schizophrenia that are caused by abnormal activity in the cognitive system. This would allow patients to get the most effective treatment possible with fewer side effects.

   edit   deselect   + to AI

 

What if there was a way to target and repurpose drugs that are already on the market to treat schizophrenia? This would be a huge development in medicine, as it would provide a more effective and efficient treatment for patients with this disease. Additionally, this would allow for further study into the gene

   edit   deselect   + to AI

 

One innovative idea would be to develop a drug that targets the taar receptor in the human brain. This drug could be used to treat conditions associated with amine agonist behavior, such as ulotaront. Another innovative idea would be to repurpose an existing drug that targets the ta

   edit   deselect   + to AI

 

An innovative idea to link these two groups of concepts would be to develop a taar receptor agonist that is relevant to psychiatric conditions. This could be a new drug or a new way of using an existing drug. The goal would be to develop a treatment that is supported by clinical evidence and data

   edit   deselect   + to AI

 

What is "democracy" and what does it have to do with "doing science" or "practicing medicine"?

   edit   deselect   + to AI

 

The emergence of advanced digital technologies is a feature of our minds, bodies, and world that could facilitate the democratic distribution of opportunities. Opportunities, not the least of which include things like scientific exploration, knowledge production, and knowledge application.

   edit   deselect   + to AI

 

However, we're not usually aware of how this technology can be leveraged. The universal human right to participate in science and engineering is an idea that is understated and an application that individuals don't often exercise. Maybe there is a tendency to think or believe that only institutional entities and their direct constituents possess the unique intellectual capacities and practical resources that are required to produce epistemic and technological goods. But buying into this notion--the notion that the means of the production of knowledge is held by an intellectually “elite” few is--firstly, just theoretically flawed--and secondly, in practice, it serves to disproportionately place decision making power and access into the hands of those who are more likely to prioritize their own perceived social or economic growth.

   edit   deselect   + to AI

 

If and when this happens, it follows that the accrual of these abstract "knowledge credits" functions to feed individualistic desires, rather than desires that benefit the whole group. Left unchecked, this compromises the frequency of cooperative engagement with others, novel propositional ideas, and solution focused ventures. In the long run, it undermines the entire scientific enterprise in the sense that the system just perpetuates the inequities and harms that “science” and “technology” are supposed to mitigate. So how do we steer the ship differently?

   edit   deselect   + to AI

 

We’re all part of this problem--regardless of what you think you can or cannot do--

   edit   deselect   + to AI

 

--therefore, we’re all part of minimizing it.

   edit   deselect   + to AI

 

So, in order to solve, what do we need to identify?

   edit   deselect   + to AI

 

What do we need to structurally alter in order to bring about functional change?

   edit   deselect   + to AI

 

Examples could include things of varied dimensions and scales. For example, we could look at problematic psychological phenomena (individual level phenomenon) or "sociopolitical” dynamics (macro or population level phenomenon) that limit access to accredited education systems...

   edit   deselect   + to AI

 

Keep Tremont space a safe environment for all

   edit   deselect   + to AI

 

physical safety (We expect that we do not verbally or physically attack each other.

   edit   deselect   + to AI

 

We expect that we do not destroy or deface property

   edit   deselect   + to AI

 

We expect that we do not use hate speech)

   edit   deselect   + to AI

 

social and emotional safety (We expect that we critique each other’s arguments constructively. We do not attack each other personally. We observe and respect each other’s boundaries. Respect the right to teach and the right to learn at all times. Be appropriate; demonstrate behavior that is considerate of the community, the campus, and yourself.

   edit   deselect   + to AI

 

Acting in an inclusive way toward everyone

   edit   deselect   + to AI

 

Clean up after self in common and classrooms

   edit   deselect   + to AI

 

Use technology for only educational purposes especially school-owned tech

   edit   deselect   + to AI

 

Maintain personal space and space of others- hands, feet, and body to self/don’t touch others

   edit   deselect   + to AI

 

Leaving the Tremont space

   edit   deselect   + to AI

 

HS may leave, with permission, without an adult only if in groups of 2 or more

   edit   deselect   + to AI

 

MS must be with an adult to leave Tremont space

   edit   deselect   + to AI

 

Staff must know where you are at all times

   edit   deselect   + to AI

 

Abstract Note

   edit   deselect   + to AI

 

In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. However, the intense search for the biological basis of mental disorders has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this paper, we show that this conceptualization can help understand why reductionist approaches in psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition, because in symptom networks there is no such common cause. Second, symptom network relations depend on the content of mental states and as such feature intentionality. Third, the strength of network relations is highly likely to partially depend

   edit   deselect   + to AI

 

on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's (1987) notion of real patterns, and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders.

   edit   deselect   + to AI

 

APA PsycNet DoiLanding page

   edit   deselect   + to AI

 

"Philosophical Issues in Psychiatry III" published on by Oxford University Press.

   edit   deselect   + to AI

 

Schizophrenia is a very complex syndrome that involves widespread brain multi-dysconnectivity. Neural circuits within specific brain regions and their links to corresponding regions are abnormal in the illness. Theoretical models of dysconnectivity and the investigation of connectomics and brain network organization have been examined in schizophrenia since the early nineteenth century. In more recent years, advancements have been achieved with the development of neuroimaging tools that have provided further clues to the structural and functional organization of the brain and global neural networks in the illness. Neural circuitry that extends across prefrontal, temporal and parietal areas of the cortex as well as limbic and other subcortical brain regions is disrupted in schizophrenia. As a result, many patients have a poor response to antipsychotic treatment and treatment failure is common. Treatment resistance that is specific to positive, negative, and cognitive domains of the

   edit   deselect   + to AI

 

illness may be related to distinct circuit phenotypes unique to treatment-refractory disease. Currently, there are no customized neural circuit-specific and targeted therapies that address this neural dysconnectivity. Investigation of targeted therapeutics that addresses particular areas of substantial regional dysconnectivity is an intriguing approach to precision medicine in schizophrenia. This review examines current findings of system and circuit-level brain dysconnectivity in treatment-resistant schizophrenia based on neuroimaging studies. Within a connectome context, on-off circuit connectivity synonymous with excitatory and inhibitory neuronal pathways is discussed. Mechanistic cellular, neurochemical and molecular studies are included with specific emphasis given to cell pathology and synaptic communication in glutamatergic and GABAergic systems. In this review we attempt to deconstruct how augmenting treatments may be applied within a circuit context to improve circuit

   edit   deselect   + to AI

 

integration and treatment response. Clinical studies that have used a variety of glutamate receptor and GABA interneuron modulators, nitric oxide-based therapies and a variety of other strategies as augmenting treatments with antipsychotic drugs are included. This review supports the idea that the methodical mapping of system-level networks to both on (excitatory) and off (inhibitory) cellular circuits specific to treatment-resistant disease may be a logical and productive approach in directing future research toward the advancement of targeted pharmacotherapeutics in schizophrenia.

   edit   deselect   + to AI

 

Schizophrenia (SCZ) is a common complex disorder with poorly understood mechanisms and no effective drug treatments. Despite the high prevalence and vast unmet medical need represented by the disease, many drug companies have moved away from the development of drugs for SCZ. Therefore, alternative strategies are needed for the discovery of truly innovative drug treatments for SCZ. Here, we present a disease phenome-driven computational drug repositioning approach for SCZ. We developed a novel drug repositioning system, PhenoPredict, by inferring drug treatments for SCZ from diseases that are phenotypically related to SCZ. The key to PhenoPredict is the availability of a comprehensive drug treatment knowledge base that we recently constructed. PhenoPredict retrieved all 18 FDA-approved SCZ drugs and ranked them highly (recall=1.0, and average ranking of 8.49%). When compared to PREDICT, one of the most comprehensive drug repositioning systems currently available, in novel predictions,

   edit   deselect   + to AI

 

PhenoPredict represented clear improvements over PREDICT in Precision-Recall (PR) curves, with a significant 98.8% improvement in the area under curve (AUC) of the PR curves. In addition, we discovered many drug candidates with mechanisms of action fundamentally different from traditional antipsychotics, some of which had published literature evidence indicating their treatment benefits in SCZ patients. In summary, although the fundamental pathophysiological mechanisms of SCZ remain unknown, integrated systems approaches to studying phenotypic connections among diseases may facilitate the discovery of innovative SCZ drugs.

   edit   deselect   + to AI

 

Since the establishment of the symptoms-based categories in the Diagnostic and Statistical Manual of Mental Disorders (DSM), Third Edition, sociologists have raised concerns about the DSM’s failure to appreciate social, contextual factors when defining mental disorders. The author describes recent developments in psychiatric nosology—the DSM-5 revision process and the emergence of the Research Domain Criteria (RDoC)—and then considers their implications for decontextualization. Drawing on in-depth interviews with psychiatrists involved in the DSM-5 controversy and a content analysis of key documents, the author first recounts the ambitious DSM-5 revisions, illuminating the DSM-5 Task Force’s embrace of dimensionalization as a solution to the problem of validity and the ultimate rejection of this ‘‘paradigm shift’’ by psychiatrists. The Task Force’s failures prompted the National Institute of Mental Health to promote RDoC as an alternative nosological framework that eschews DSM

   edit   deselect   + to AI

 

categories altogether. Next, the author explores the ramifications of these events for decontextualization, which neither DSM-5 nor RDoC explicitly addresses, demonstrating how RDoC is poised to escalate decontextualization through its brain-centric conceptualization of mental disorders. To counteract these developments, sociologists should continue to promote ways of defining mental distress that underscore its social embeddedness.

   edit   deselect   + to AI

 

Purpose – Evidence-based medicine (EBM) is a technical and scientific paradigm in clinical practice that has delivered major improvements in the outcome of care in medicine and surgery. However, its value in psychiatry is much less clear. The purpose of the paper is thus to examine its value by subjecting empirical evidence from EBM to a conceptual analysis using the philosophy of Thomas Kuhn. Design/methodology/approach – The authors examine evidence drawn from meta-analyses of RCTs investigating the efficacy of specific treatments for depression in the form of antidepressant drugs and CBT. This shows that the non-specific aspects of treatment, the placebo effect and the quality of the therapeutic alliance as seen by the patient, are more important in determining outcome than the specific elements (active drug, specific therapeutic elements of CBT).

   edit   deselect   + to AI

 

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the

   edit   deselect   + to AI

 

right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise.

   edit   deselect   + to AI

 

Explanations of psychological phenomena seem to generate more public interest when they contain neuroscientific information. Even irrelevant neuroscience information in an explanation of a psychological phenomenon may interfere with people’s abilities to critically consider the underlying logic of this explanation. We tested this hypothesis by giving naïve adults, students in a neuroscience course, and neuroscience experts brief descriptions of psychological phenomena followed by one of four types of explanation, according to a 2 (good explanation vs. bad explanation) × 2 (without neuroscience vs. with neuroscience) design. Crucially, the neuroscience information was irrelevant to the logic of the explanation, as confirmed by the expert subjects. Subjects in all three groups judged good explanations as more satisfying than bad ones. But subjects in the two nonexpert groups additionally judged that explanations with logically irrelevant neuroscience information were more satisfying

   edit   deselect   + to AI

 

than explanations without. The neuroscience information had a particularly striking effect on nonexperts’ judgments of bad explanations, masking otherwise salient problems in these explanations.

   edit   deselect   + to AI

 

Physicians and other medical practitioners make untold numbers of judgments about patient care on a daily, weekly, and monthly basis. These judgments fall along a number of spectrums, from the mundane to the tragic, from the obvious to the challenging. Under the rubric of evidence-based medicine, these judgments will be informed by the robust conclusions of medical research. In the ideal circumstance medical research makes the best decision obvious to the trained professional. Even when practice approximates this ideal, it does so unevenly. Judgments in medical practice are always accompanied by uncertainty, and this uncertainty is a fickle companion—constant in its presence but inconstant in its expression. This feature of medical judgments gives rise to the moral responsibility of medical practitioners to be epistemically humble. This requires the recognition and communication of the uncertainty that accompanies their judgment as well as a commitment to avoiding intuitive

   edit   deselect   + to AI

 

innovations.

   edit   deselect   + to AI

 

Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as ‘too difficult’ a challenge to warrant major investment. Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials. My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry’s concerns.

   edit   deselect   + to AI

 

In this article, we examine the different ways in which Thomas Szasz and Michel Foucault have challenged dominant perspectives within psychiatry. We identify, analyze, and compare the central elements of their respective discourses on psychiatry and show that although they are often bracketed together, in fact there are certain fundamental differences between Szasz and Foucault. Of most importance is their contrasting ways of characterizing the nature and role of critical thought. Whereas Szasz’s analysis is predicated on a number of binary distinctions, Foucault works to overcome such distinctions. In the past ten years, a new movement of critical psychiatry has emerged. Although this shares certain concerns with the critical psychiatry of the 1960s and 1970s, there are substantial differences. We argue that this discourse is more resonant with the Foucauldian approach.

   edit   deselect   + to AI

 

Reducing stigma is crucial for facilitating recovery from psychological problems. Viewing these problems biomedically may reduce the tendency to blame affected persons, but critics have cautioned that it could also increase other facets of stigma. We report on the first meta-analytic review of the effects of biogenetic explanations on stigma. A comprehensive search yielded 28 eligible experimental studies. Four separate meta-analyses (Ns = 1207–3469) assessed the effects of biogenetic explanations on blame, perceived dangerousness, social distance, and prognostic pessimism. We found that biogenetic explanations reduce blame (Hedges g = − 0.324) but induce pessimism (Hedges g = 0.263). We also found that biogenetic explanations increase endorsement of the stereotype that people with psychological problems are dangerous (Hedges g = 0.198), although this result could reflect publication bias. Finally, we found that biogenetic explanations do not typically affect social distance. Promoting

   edit   deselect   + to AI

 

biogenetic explanations to alleviate blame may induce pessimism and set the stage for self-fulfilling prophecies that could hamper recovery from psychological problems.

   edit   deselect   + to AI

 

People with serious mental illness get sick and die 10--20 years earlier than their same age cohort. The social determinants are many: stigma associated with mental illness, poverty, ethnicity-based discrimination, higher rates of smoking and alcohol and drug use, and poor diet and exercise patterns, to name a few. Although multiple interventions have emerged as ways to combat these health challenges, additional research is necessary for the continued development and evaluation of strategies. This context serves as the springboard for Health and Wellness in People Living With Serious Mental Illness. Through multiple case vignettes, the book delves into the challenges of health and wellness for people with mental illness -- including those listed above -- summarizing the research on mortality and morbidity in this group as well as information about the status quo on wellness. It also provides a thorough description of community-based participatory research (CBPR), an approach that

   edit   deselect   + to AI

 

includes people in a community as partners in all facets of research, rather than just the subjects of that research. CBPR acts as the lens through which this guide considers solutions to these health problems, including integrated services and patient-centered medical homes; medical practices that diminish the iatrogenic effects of psychiatry; psychoeducation; interpersonal supports; and shared decision-making. Co-edited by Patrick Corrigan, with a 30-year history in services research, and Sonya Ballentine, a community-based member of a CBPR team, this volume offers a grounded, real-world illustration of CBPR in practice. Students of psychiatry, practicing clinicians, primary care providers, allied health professionals, policy makers -- all will find, in the pages of this book, a nuanced portrait of the health challenges patients with mental illness face, possible treatment options, and future directions for the field.

   edit   deselect   + to AI

 

Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding of schizophrenia pathogenesis could shed light on actions of current drugs and reveal novel druggable pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks and uncover drug-disease relationships. Polygenic overlap between schizophrenia risk genes and antipsychotic drug targets has been demonstrated. However, the specific genes and pathways constituting this overlap are undetermined. Risk genes of polygenic disorders do not operate in isolation, but in combination with other genes. Thus, we utilized protein-protein interaction networks (interactome) to map antipsychotic drug targets (n=88) to networks of schizophrenia risk genes (n=328). Our results showed that schizophrenia risk genes were significantly localized in the interactome (p=0.0015), forming a

   edit   deselect   + to AI

 

distinct disease module. Core genes of the module were enriched for genes involved in developmental biology and cognition, which may have a central role in schizophrenia etiology. Intriguingly, antipsychotic drug targets overlapped with the core disease module and comprised multiple pathways beyond dopamine. Some important risk genes like CHRN, PCDH and HCN families were not connected to existing antipsychotics, but may be suitable targets for novel drugs or drug repurposing opportunities to treat other aspects of schizophrenia such as cognitive dysfunction and negative symptoms. This network medicine approach provides a platform to collate information of disease genetics and drug-gene interactions to shift focus from development of antipsychotics to multi-target anti-schizophrenia drugs. This approach is transferable to other diseases.

   edit   deselect   + to AI

 

OBJECTIVE: Computational drug repositioning can lead to a considerable reduction in cost and time in any drug development process. Recent approaches have addressed the network-based nature of biological information for performing complex prioritization tasks. In this work, we propose a new methodology based on heterogeneous network prioritization that can aid researchers in the drug repositioning process. METHODS: We have developed DrugNet, a new methodology for drug-disease and disease-drug prioritization. Our approach is based on a network-based prioritization method called ProphNet which has recently been developed by the authors. ProphNet is able to integrate data from complex networks involving a wide range of types of elements and interactions. In this work, we built a network of interconnected drugs, proteins and diseases and applied DrugNet to different types of tests for drug repositioning. RESULTS: We tested the performance of our approach on different validation tests,

   edit   deselect   + to AI

 

including cross validation and tests based on real clinical trials. DrugNet achieved a mean AUC value of 0.9552±0.0015 in 5-fold cross validation tests, and a mean AUC value of 0.8364 for tests based on recent clinical trials (phases 0-4) not present in our data. These results suggest that DrugNet could be very useful for discovering new drug uses. We also studied specific cases of particular interest, proving the benefits of heterogeneous data integration in this problem. CONCLUSIONS: Our methodology suggests that new drugs can be repositioned by generating ranked lists of drugs based on a given disease query or vice versa. Our study shows that the simultaneous integration of information about diseases, drugs and targets can lead to a significant improvement in drug repositioning tasks. DrugNet is available as a web tool from http://genome2.ugr.es/drugnet/ (accessed 23.09.14). Matlab source code is also available on the website.

   edit   deselect   + to AI

 

Until recently, it was thought that there is no neuronal regeneration and neuron loss is irreversible, but today the exist-ence of neural regeneration and neural plasticity have been documented. The effectiveness of stem cell treatment in nu-merous degenerative diseases, as well as some neurodegenerative diseases, has created hopes toward the use of stem cell treatment in schizophrenia, which is a disease that progresses with neuronal degeneration and loss of neurons, and is characterized with worsening clinical outcomes and impairment.

   edit   deselect   + to AI

 

The communication of uncertainty in clinical evidence is an important endeavor that poses difficult conceptual, methodological, and ethical problems. Conceptual problems include logical paradoxes in the meaning of probability and “ambiguity”— second-order uncertainty arising from the lack of reliability, credibility, or adequacy of probability information. Methodological problems include questions about optimal methods for representing fundamental uncertainties and for communicating these uncertainties in clinical practice. Ethical problems include questions about whether communicating uncertainty enhances or diminishes patient autonomy and produces net benefits or harms. This article reviews the limited but growing literature on these problems and efforts to address them and identifies key areas of focus for future research. It is argued that the critical need moving forward is for greater conceptual clarity and consistent representational methods that make the meaning of various

   edit   deselect   + to AI

 

uncertainties understandable, and for clinical interventions to support patients in coping with uncertainty in decision making.

   edit   deselect   + to AI

 

Uncertainty is an inherent part of knowledge, and yet in an era of contested expertise, many shy away from openly communicating their uncertainty about what they know, fearful of their audience's reaction. But what effect does communication of such epistemic uncertainty have? Empirical research is widely scattered across many disciplines. This interdisciplinary review structures and summarizes current practice and research across domains, combining a statistical and psychological perspective. This informs a framework for uncertainty communication in which we identify three objects of uncertainty—facts, numbers and science—and two levels of uncertainty: direct and indirect. An examination of current practices provides a scale of nine expressions of direct uncertainty. We discuss attempts to codify indirect uncertainty in terms of quality of the underlying evidence. We review the limited literature about the effects of communicating epistemic uncertainty on cognition, affect, trust and

   edit   deselect   + to AI

 

decision-making. While there is some evidence that communicating epistemic uncertainty does not necessarily affect audiences negatively, impact can vary between individuals and communication formats. Case studies in economic statistics and climate change illustrate our framework in action. We conclude with advice to guide both communicators and future researchers in this important but so far rather neglected field.

   edit   deselect   + to AI

 

In recent years, the network approach to psychopathology has been advanced as an alternative way of conceptualizing mental disorders. In this approach, mental disorders arise from direct interactions between symptoms. Although the network approach has led to many novel methodologies and substantive applications, it has not yet been fully articulated as a scientific theory of mental disorders. The present paper aims to develop such a theory, by postulating a limited set of theoretical principles regarding the structure and dynamics of symptom networks. At the heart of the theory lies the notion that symptoms of psychopathology are causally connected through myriads of biological, psychological and societal mechanisms. If these causal relations are sufficiently strong, symptoms can generate a level of feedback that renders them self-sustaining. In this case, the network can get stuck in a disorder state. The network theory holds that this is a general feature of mental disorders, which

   edit   deselect   + to AI

 

can therefore be understood as alternative stable states of strongly connected symptom networks. This idea naturally leads to a comprehensive model of psychopathology, encompassing a common explanatory model for mental disorders, as well as novel definitions of associated concepts such as mental health, resilience, vulnerability and liability. In addition, the network theory has direct implications for how to understand diagnosis and treatment, and suggests a clear agenda for future research in psychiatry and associated disciplines.

   edit   deselect   + to AI

 

BindingDB, www.bindingdb.org, is a publicly accessible database of experimental protein-small molecule interaction data. Its collection of over a million data entries derives primarily from scientific articles and, increasingly, US patents. BindingDB provides many ways to browse and search for data of interest, including an advanced search tool, which can cross searches of multiple query types, including text, chemical structure, protein sequence and numerical affinities. The PDB and PubMed provide links to data in BindingDB, and vice versa; and BindingDB provides links to pathway information, the ZINC catalog of available compounds, and other resources. The BindingDB website offers specialized tools that take advantage of its large data collection, including ones to generate hypotheses for the protein targets bound by a bioactive compound, and for the compounds bound by a new protein of known sequence; and virtual compound screening by maximal chemical similarity, binary kernel

   edit   deselect   + to AI

 

discrimination, and support vector machine methods. Specialized data sets are also available, such as binding data for hundreds of congeneric series of ligands, drawn from BindingDB and organized for use in validating drug design methods. BindingDB offers several forms of programmatic access, and comes with extensive background material and documentation. Here, we provide the first update of BindingDB since 2007, focusing on new and unique features and highlighting directions of importance to the field as a whole.

   edit   deselect   + to AI

 

Background: Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. Methods: In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of applications, and lists of relevant references. Results: This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term,

   edit   deselect   + to AI

 

where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic.

   edit   deselect   + to AI

 

Drug-drug interaction (DDI) can trigger many adverse effects in patients and has emerged as a threat to medicine and public health. Despite the continuous information accumulation of clinically significant DDIs, there are few open-access knowledge systems dedicated to the curation of DDI associations. To facilitate the clinicians to screen for dangerous drug combinations and improve health systems, we present DDInter, a curated DDI database with comprehensive data, practical medication guidance, intuitive function interface, and powerful visualization to the scientific community. Currently, DDInter contains about 0.24M DDI associations connecting 1833 approved drugs (1972 entities). Each drug is annotated with basic chemical and pharmacological information and its interaction network. For DDI associations, abundant and professional annotations are provided, including severity, mechanism description, strategies for managing potential side effects, alternative medications, etc. The drug

   edit   deselect   + to AI

 

entities and interaction entities are efficiently cross-linked. In addition to basic query and browsing, the prescription checking function is developed to facilitate clinicians to decide whether drugs combinations can be used safely. It can also be used for informatics-based DDI investigation and evaluation of other prediction frameworks. We hope that DDInter will prove useful in improving clinical decision-making and patient safety. DDInter is freely available, without registration, at http://ddinter.scbdd.com/.

   edit   deselect   + to AI

 

Psychedelics have inspired new hope for treating brain disorders, as they seem to be unlike any treatments currently available. Not only do they produce sustained therapeutic effects following a single administration, they also appear to have broad therapeutic potential, demonstrating efficacy for treating depression, post-traumatic stress disorder (PTSD), anxiety disorders, substance abuse disorder, and alcohol use disorder, among others. Psychedelics belong to a more general class of compounds known as psychoplastogens, which robustly promote structural and functional neural plasticity in key circuits relevant to brain health. Here we discuss the importance of structural plasticity in the treatment of neuropsychiatric diseases, as well as the evidence demonstrating that psychedelics are among the most effective chemical modulators of neural plasticity studied to date. Furthermore, we provide a theoretical framework with the potential to explain why psychedelic compounds produce

   edit   deselect   + to AI

 

long-lasting therapeutic effects across a wide range of brain disorders. Despite their promise as broadly efficacious neurotherapeutics, there are several issues associated with psychedelic-based medicines that drastically limit their clinical scalability. We discuss these challenges and how they might be overcome through the development of non-hallucinogenic psychoplastogens. The clinical use of psychedelics and other psychoplastogenic compounds marks a paradigm shift in neuropsychiatry toward therapeutic approaches relying on the selective modulation of neural circuits with small molecule drugs. Psychoplastogen research brings us one step closer to actually curing mental illness by rectifying the underlying pathophysiology of disorders like depression, moving beyond simply treating disease symptoms. However, determining how to most effectively deploy psychoplastogenic medicines at scale will be an important consideration as the field moves forward.

   edit   deselect   + to AI

 

What is the most effective treatment for patients with schizophrenia?

   edit   deselect   + to AI

 

What is the most effective treatment for patients with schizophrenia?

   edit   deselect   + to AI

 

What are the most recent evidence-based approaches for treating drug-resistant diseases in developing communities?

   edit   deselect   + to AI

 

What is the evidence for repositioning drugs for scz in recent years?

   edit   deselect   + to AI

 

What are the most recent evidence-based approaches to repositioning drugs for the treatment of scz?

   edit   deselect   + to AI

 

One possible innovative idea is to develop a community-based approach to drug development and testing. This approach would involve engaging community members in the design and implementation of clinical trials, as well as in the development and testing of new treatments. This approach would benefit from the expertise of both community members and medical

   edit   deselect   + to AI

 

The idea is to develop a community-based approach to testing new drugs for scz. The community would be involved in every step of the process, from drug development to target selection to testing. This would ensure that the community is invested in the success of the project and that the most effective treatments

   edit   deselect   + to AI

 

The development of a community-based approach to testing new drugs for scz.

   edit   deselect   + to AI

 

A recent study found that drug repositioning – the process of finding new uses for existing drugs – is a promising approach for developing new treatments for diseases with high unmet medical needs, such as scz. The study's findings provide evidence that repositioning drugs from other therapeutic fields may be

   edit   deselect   + to AI

 

× ⁝⁝ 
        
Show Nodes with Degree > 0:

0 0

Total Nodes Shown:
 extend

Filter Graphs:


Filter Time Range
from: 0
to: 0


Recalculate Metrics Reset Filters
Show Labels for Nodes > 0 size:

0 0

Default Label Size: 0

0 20



Edges Type:



Layout Type:


 

Reset to Default
semantic variability:
×  ⁝⁝ 
×  ⁝⁝ 
Semantic Variability Score
— modulates diversity of the discourse network  how it works?
The score is calculated based on how modular the structure of the graph is (> 0.4 means the clusters are distinct and separate from one another = multiple perspectives). It also takes into account how the most influential nodes are dispersed among those clusters (higher % = lower concentration of power in a particular cluster).
Actionable Insight:

N/A

We distinguish 4 states of variability in your discourse. We recommend that a well-formed discourse should go through every stage during its evolution (in several iterations).

  1 - (bottom left quadrant) — biased — low variability, low diversity, one central idea (genesis and introduction stage).
  2 - (top right) - focused - medium variability and diversity, several concepts form a cluster (coherent communication stage).
  3 - (bottom right) - diversified — there are several distinct clusters of main ideas present in text, which interact on the global level but maintain specificity (optimization and reflection stage).
  4 - (left top) — dispersed — very high variability — there are disjointed bits and pieces of unrelated ideas, which can be used to construct new ideas (creative reformulation stage).

Read more in the cognitive variability help article.
Generate AI Suggestions
Your Workflow Variability:
 
Shows to what extent you explored all the different states of the graph, from uniform and regular to fractal and complex. Read more in the cognitive variability help article.

You can increase the score by adding content into the graph (your own and AI-generated), as well as removing the nodes from the graph to reveal latent topics and hidden patterns.
Phases to Explore:
AI Suggestions  
×  ⁝⁝ 
     
Main Topical Clusters:

please, add your data to display the stats...
+     full table   ?     Show AI Categories

The topical clusters are comprised of the nodes (words) that tend to co-occur together in the same context (next to each other).

We use a combination of clustering and graph community detection algorithm (Blondel et al based on Louvain) to identify the groups of nodes are more densely connected together than with the rest of the network. They are aligned closer to each other on the graph using the Force Atlas algorithm (Jacomy et al) and are given a distinct color.
Most Influential Elements:
please, add your data to display the stats...
+     Reveal Non-obvious   ?

AI Summarize Graph   AI Article Outline

We use the Jenks elbow cutoff algorithm to select the top prominent nodes that have significantly higher influence than the rest.

Click the Reveal Non-obvious button to remove the most influential words (or the ones you select) from the graph, to see what terms are hiding behind them.

The most influential nodes are either the ones with the highest betweenness centrality — appearing most often on the shortest path between any two randomly chosen nodes (i.e. linking the different distinct communities) — or the ones with the highest degree.
Network Structure:
N/A
?
The network structure indicates the level of its diversity. It is based on the modularity measure (>0.4 for medium, >0.65 for high modularity, measured with Louvain (Blondel et al 2008) community detection algorithm) in combination with the measure of influence distribution (the entropy of the top nodes' distribution among the top clusters), as well as the the percentage of nodes in the top community.


Download: TXT Report  CSV Report  More Options
Discourse Structure Advice:
N/A
Structural Gap Insight
(topics that could be better linked):
N/A
Highlight in Network   ↻ Show Another Gap   ?  
AI: Bridge the Gap   AI: Article Outline
 
A structural gap shows the two distinct communities (clusters of words) in this graph that are important, but not yet connected. That's where the new potential and innovative ideas may reside.

This measure is based on a combination of the graph's connectivity and community structure, selecting the groups of nodes that would either make the graph more connected if it's too dispersed or that would help maintain diversity if it's too connected.

Latent Topical Connectors
(less visible terms that link important topics):
N/A
?   ↻ Undo Selection
AI: Select & Generate Content
These are the latent brokers between the topics: the nodes that have an unusually high rate of influence (betweenness centrality) to their freqency — meaning they may appear not as often as the most influential nodes but they are important narrative shifting points.

These are usually brokers between different clusters / communities of nodes, playing not easily noticed and yet important role in this network, like the "grey cardinals" of sorts.

Emerging Keywords
N/A

Evolution of Topics
(number of occurrences per text segment) ?
The chart shows how the main topics and the most influential keywords evolved over time. X-axis: time period (split into 10% blocks). Y-axis: cumulative number of occurrences.

Drag the slider to see how the narrative evolved over time. Select the checkbox to recalculate the metrics at every step (slower, but more precise).

 
Main Topics
(according to Latent Dirichlet Allocation):
loading...
 ?  

LDA stands for Latent Dirichlet Allocation — it is a topic modelling algorithm based on calculating the maximum probability of the terms' co-occurrence in a particular text or a corpus.

We provide this data for you to be able to estimate the precision of the default InfraNodus topic modeling method based on text network analysis.
Most Influential Words
(main topics and words according to LDA):
loading...

We provide LDA stats for comparison purposes only. It works with English-language texts at the moment. More languages are coming soon, subscribe @noduslabs to be informed.

Sentiment Analysis


positive: | negative: | neutral:
reset filter    ?  

We analyze the sentiment of each statement to see whether it's positive, negative, or neutral. You can filter the statements by sentiment (clicking above) and see what kind of topics correlate with every mood.

The approach is based on AFINN and Emoji Sentiment Ranking

 
Use the Bert AI model for English, Dutch, German, French, Spanish and Italian to get more precise results (slower). Standard model is faster, works for English only, is less precise, and is based on a fixed AFINN dictionary.

Keyword Relations Analysis:

please, select the node(s) on the graph see their connections...
+   ⤓ download CSV   ?

Use this feature to compare contextual word co-occurrences for a group of selected nodes in your discourse. Expand the list by clicking the + button to see all the nodes your selected nodes are connected to. The total influence score is based on betweenness centrality measure. The higher is the number, the more important are the connections in the context of the discourse.
Top Relations in 4-grams
(bidirectional, for directional bigrams see the CSV table below):

⤓ Download   ⤓ Directed Bigrams CSV   ?

The most prominent relations between the nodes that exist in this graph are shown above. We treat the graph as undirected by default. Occurrences shows the number of the times a relationship appears in a 4-gram window. Weight shows the weight of that relation.

As an option, you can also downloaded directed bigrams above, in case the direction of the relations is important (for any application other than language).

Text Statistics:
Word Count Unique Lemmas Characters Lemmas Density
0
0
0
0
Text Network Statistics:
Show Overlapping Nodes Only

⤓ Download as CSV  ⤓ Download an Excel File
Network Structure Insights
 
mind-viral immunity:
N/A
  ?
stucture:
N/A
  ?
The higher is the network's structure diversity and the higher is the alpha in the influence propagation score, the higher is its mind-viral immunity — that is, such network will be more resilient and adaptive than a less diverse one.

In case of a discourse network, high mind-viral immunity means that the text proposes multiple points of view and propagates its influence using both highly influential concepts and smaller, secondary topics.
The higher is the diversity, the more distinct communities (topics) there are in this network, the more likely it will be pluralist.
The network structure indicates the level of its diversity. It is based on the modularity measure (>0.4 for medium, >0.65 for high modularity, measured with Louvain (Blondel et al 2008) community detection algorithm) in combination with the measure of influence distribution (the entropy of the top nodes' distribution among the top clusters), as well as the the percentage of nodes in the top community.

Modularity
0
Influence Distribution
0
%
Topics Nodes in Top Topic Components Nodes in Top Comp
0
0
%
0
0
%
Nodes Av Degree Density Weighed Betweenness
0
0
0
0
 

Narrative Influence Propagation:
  ?
The chart above shows how influence propagates through the network. X-axis: lemma to lemma step (narrative chronology). Y-axis: change of influence.

The more even and rhythmical this propagation is, the stronger is the central idea or agenda (see alpha exponent below ~ 0.5 or less).

The more variability can be seen in the propagation profile, the less is the reliance on the main concepts (agenda), the stronger is the role of secondary topical clusters in the narrative.
propagation dynamics: | alpha exponent: (based on Detrended Fluctuation Analysis of influence) ?   show the chart
We plot the narrative as a time series of influence (using the words' betweenness score). We then apply detrended fluctuation analysis to identify fractality of this time series, plotting the log2 scales (x) to the log2 of accumulated fluctuations (y). If the resulting loglog relation can be approximated on a linear polyfit, there may be a power-law relation in how the influence propagates in this narrative over time (e.g. most of the time non-influential words, occasionally words with a high influence).

Using the alpha exponent of the fit (which is closely related to Hurst exponent)), we can better understand the nature of this relation: uniform (pulsating | alpha <= 0.65), variable (stationary, has long-term correlations | 0.65 < alpha <= 0.85), fractal (adaptive | 0.85 < alpha < 1.15), and complex (non-stationary | alpha >= 1.15).

For maximal diversity, adaptivity, and plurality, the narrative should be close to "fractal" (near-critical state). For fiction, essays, and some forms of poetry — "uniform". Informative texts will often have "variable + stationary" score. The "complex" state is an indicator that the text is always shifting its state.

Degree Distribution:
  calculate & show   ?
(based on kolmogorov-smirnov test) ?   switch to linear
Using this information, you can identify whether the network has scale-free / small-world (long-tail power law distribution) or random (normal, bell-shaped distribution) network properties.

This may be important for understanding the level of resilience and the dynamics of propagation in this network. E.g. scale-free networks with long degree tails are more resilient against random attacks and will propagate information across the whole structure better.
If a power-law is identified, the nodes have preferential attachment (e.g. 20% of nodes tend to get 80% of connections), and the network may be scale-free, which may indicate that it's more resilient and adaptive. Absence of power law may indicate a more equalized distribution of influence.

Kolmogorov-Smirnov test compares the distribution above to the "ideal" power-law ones (^1, ^1.5, ^2) and looks for the best fit. If the value d is below the critical value cr it is a sign that the both distributions are similar.
Please, enter a search query to visualize the difference between what people search for (related queries) and what they actually find (search results):

 
We will build two graphs:
1) Google search results for your query;
2) Related searches for your query (Google's SERP);
Click the Missing Content tab to see the graph that shows the difference between what people search for and what they actually find, indicating the content you could create to fulfil this gap.
Please, enter a search query to discover what else people are searching for (from Google search or AdWords suggestions):

 
We will build a graph of the search phrases related to your query (Google's SERP suggestions).
Find a market niche for a certain product, category, idea or service: what people are looking for but cannot yet find*

 
We will build two graphs:
1) the content that already exists when you make this search query (informational supply);
2) what else people are searching for when they make this query (informational demand);
You can then click the Niche tab to see the difference between the supply and the demand — what people need but do not yet find — the opportunity gap to fulfil.
Please, enter your query to visualize Google search results as a graph, so you can learn more about this topic:

   advanced settings    add data manually
Discover the main topics, recurrent themes, and missing connections in any text or an article:  
Discover the main themes, sentiment, recurrent topics, and hidden connections in open survey responses:  
Discover the main themes, sentiment, recurrent topics, and hidden connections in customer product reviews:  
Enter a search query to analyze the Twitter discourse around this topic (last 7 days):

     advanced settings    add data manually

Enter a topic or a @user to analyze its social network on Twitter:

 advanced settings    add data manually

Sign Up