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https://www.readbyqxmd.com/read/28530802/discovery-of-n-5-fluoropyridin-2-yl-6-methyl-4-pyrimidin-5-yloxy-picolinamide-vu0424238-a-novel-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-subtype-5-selected-for-clinical-evaluation
#1
Andrew S Felts, Alice L Rodriguez, Anna L Blobaum, Ryan D Morrison, Brittney S Bates, Analisa Thompson Gray, Jerri M Rook, Mohammed N Tantawy, Frank W Byers, Sichen Chang, Daryl F Venable, Vincent B Luscombe, Gilles D Tamagnan, Colleen M Niswender, J Scott Daniels, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28527163/pharmacotherapy-of-insomnia-and-current-updates
#2
REVIEW
Arup Kumar Misra, Pramod Kumar Sharma
Insomnia is highly prevalent and is associated with a range of psychological, psychiatric, and medical conditions. Insomnia affects health by influencing cognitive, emotional and social functioning. Circadian and sleep homeostatic processes play an important role in insomnia development and its maintenance. Several efficacious treatments, both pharmacologic and non-pharmacologic, exist for the management of insomnia. Among non-pharmacologic treatments including stimulus control therapy, sleep restriction, relaxation, sleep hygiene and cognitive therapy have been shown to be efficacious...
April 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28523977/the-application-of-deep-brain-stimulation-in-the-treatment-of-psychiatric-disorders
#3
Ilse Graat, Martijn Figee, Damiaan Denys
Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex neuroanatomy of psychiatric disorders. However, for obsessive-compulsive disorder (OCD) DBS is now an accepted treatment. This study first reviews clinical outcomes and mechanisms of DBS for OCD, and then discusses these results in an overview of current and future psychiatric applications, including DBS for mood disorders, Tourette's syndrome, addiction, anorexia nervosa, autism, schizophrenia, and anxiety disorders...
April 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/28523558/epigenome-editing-in-the-brain
#4
Pavel Bashtrykov, Albert Jeltsch
Epigenome editing aims for an introduction or removal of chromatin marks at a defined genomic region using artificial EpiEffectors resulting in a modulation of the activity of the targeted functional DNA elements. Rationally designed EpiEffectors consist of a targeting DNA-binding module (such as a zinc finger protein, TAL effector, or CRISPR/Cas complex) and usually, but not exclusively, a catalytic domain of a chromatin-modifying enzyme. Epigenome editing opens a completely new strategy for basic research of the central nervous system and causal treatment of psychiatric and neurological diseases, because rewriting of epigenetic information can lead to the direct and durable control of the expression of disease-associated genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28520584/eating-disorders-and-bone-metabolism-in-women
#5
Lauren Robinson, Nadia Micali, Madhusmita Misra
PURPOSE OF REVIEW: Eating Disorders are psychiatric disorders associated with a high risk for low bone mineral density (BMD) and fractures. Low BMD is a consequence of undernutrition, changes in body composition, and hormonal alterations. This review summarizes recent findings regarding novel strategies for assessing bone outcomes in patients with eating disorders, factors contributing to altered bone metabolism, and possible therapeutic strategies. RECENT FINDINGS: Emerging research in this field suggests that not only anorexia nervosa, but also bulimia nervosa results in lower BMD compared to controls...
May 16, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28517032/novel-psychoactive-substance-consumption-is-more-represented-in-bipolar-disorder-than-in-psychotic-disorders-a-multicenter-observational-study
#6
Tiziano Acciavatti, Matteo Lupi, Rita Santacroce, Andrea Aguglia, Luigi Attademo, Laura Bandini, Paola Ciambrone, Giulia Lisi, Giovanni Migliarese, Federica Pinna, Diego Quattrone, Michele Ribolsi, Maria Salvina Signorelli, Salvatore Calò, Fabrizio Schifano, Massimo di Giannantonio, Giovanni Martinotti
OBJECTIVE: Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this multicentre survey is to investigate the consumption of a number of psychoactive substances in a young psychiatric sample. METHODS: Between December 2013 and September 2015, a questionnaire was administered in 10 Italian psychiatric care facilities to a sample of 671 patients, aged 18-26 (mean age 22...
May 18, 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28513607/variants-in-ttc25-affect-autistic-trait-in-patients-with-autism-spectrum-disorder-and-general-population
#7
Dina Vojinovic, Nathalie Brison, Shahzad Ahmad, Ilse Noens, Irene Pappa, Lennart C Karssen, Henning Tiemeier, Cornelia M van Duijn, Hilde Peeters, Najaf Amin
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study...
May 17, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28507316/autism-spectrum-disorders-and-autistic-traits-share-genetics-and-biology
#8
J Bralten, K J van Hulzen, M B Martens, T E Galesloot, A Arias Vasquez, L A Kiemeney, J K Buitelaar, J W Muntjewerff, B Franke, G Poelmans
Autism spectrum disorders (ASDs) and autistic traits in the general population may share genetic susceptibility factors. In this study, we investigated such potential overlap based on common genetic variants. We developed and validated a self-report questionnaire of autistic traits in adults. We then conducted genome-wide association studies (GWASs) of six trait scores derived from the questionnaire through exploratory factor analysis in 1981 adults from the general population. Using the results from the Psychiatric Genomics Consortium GWAS of ASDs, we observed genetic sharing between ASDs and the autistic traits 'childhood behavior', 'rigidity' and 'attention to detail'...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28506904/ordinal-convolutional-neural-networks-for-predicting-rdoc-positive-valence-psychiatric-symptom-severity-scores
#9
Anthony Rios, Ramakanth Kavuluru
BACKGROUND: The CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing (NLP) provided a set of 1000 neuropsychiatric notes to participants as part of a competition to predict psychiatric symptom severity scores. This paper summarizes our methods, results, and experiences based on our participation in the second track of the shared task. OBJECTIVE: Classical methods of text classification usually fall into one of three problem types: binary, multi-class, and multi-label classification...
May 12, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28504703/polygenic-transmission-disequilibrium-confirms-that-common-and-rare-variation-act-additively-to-create-risk-for-autism-spectrum-disorders
#10
Daniel J Weiner, Emilie M Wigdor, Stephan Ripke, Raymond K Walters, Jack A Kosmicki, Jakob Grove, Kaitlin E Samocha, Jacqueline I Goldstein, Aysu Okbay, Jonas Bybjerg-Grauholm, Thomas Werge, David M Hougaard, Jacob Taylor, David Skuse, Bernie Devlin, Richard Anney, Stephan J Sanders, Somer Bishop, Preben Bo Mortensen, Anders D Børglum, George Davey Smith, Mark J Daly, Elise B Robinson
Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD...
May 15, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28496402/cortico-striatal-thalamic-loop-circuits-of-the-orbitofrontal-cortex-promising-therapeutic-targets-in-psychiatric-illness
#11
REVIEW
Peter Fettes, Laura Schulze, Jonathan Downar
Corticostriatal circuits through the orbitofrontal cortex (OFC) play key roles in complex human behaviors such as evaluation, affect regulation and reward-based decision-making. Importantly, the medial and lateral OFC (mOFC and lOFC) circuits have functionally and anatomically distinct connectivity profiles which differentially contribute to the various aspects of goal-directed behavior. OFC corticostriatal circuits have been consistently implicated across a wide range of psychiatric disorders, including major depressive disorder (MDD), obsessive compulsive disorder (OCD), and substance use disorders (SUDs)...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28495813/trends-in-the-supply-of-california-s-emergency-departments-and-inpatient-services-2005-2014-a-retrospective-analysis
#12
Jessica L Chow, Matthew J Niedzwiecki, Renee Y Hsia
OBJECTIVES: Given increasing demand for emergency care, there is growing concern over the availability of emergency department (ED) and inpatient resources. Existing studies of ED bed supply are dated and often overlook hospital capacity beyond ED settings. We described recent statewide trends in the capacity of ED and inpatient hospital services from 2005 to 2014. DESIGN: Retrospective analysis. SETTING: Using California hospital data, we examined the absolute and per admission changes in ED beds and inpatient beds in all hospitals from 2005 to 2014...
May 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28495341/estimation-of-the-prevalence-of-adverse-drug-reactions-from-social-media
#13
Thin Nguyen, Mark E Larsen, Bridianne O'Dea, Dinh Phung, Svetha Venkatesh, Helen Christensen
This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora...
June 2017: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/28495022/delineating-the-joint-hierarchical-structure-of-clinical-and-personality-disorders-in-an-outpatient-psychiatric-sample
#14
Miriam K Forbes, Roman Kotov, Camilo J Ruggero, David Watson, Mark Zimmerman, Robert F Krueger
BACKGROUND: A large body of research has focused on identifying the optimal number of dimensions - or spectra - to model individual differences in psychopathology. Recently, it has become increasingly clear that ostensibly competing models with varying numbers of spectra can be synthesized in empirically derived hierarchical structures. METHODS AND MATERIALS: We examined the convergence between top-down (bass-ackwards or sequential principal components analysis) and bottom-up (hierarchical agglomerative cluster analysis) statistical methods for elucidating hierarchies to explicate the joint hierarchical structure of clinical and personality disorders...
April 29, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28494748/the-novelty-of-bupropion-as-a-dopaminergic-antidepressant-for-the-treatment-of-adult-attention-deficit-hyperactive-disorder
#15
Kanit Tha Deang, Hatta Sidi, Hazli Zakaria, Raja Lope Adam, Srijit Das, Nurul Hazwani Hatta, Muhammad Hatta, Kok Wei Wee
Attention deficit hyperactive disorder (ADHD), a hyperactivity disorder that is prevalent among children may continue as an adulthood attention deficit. To date, treating an individual with an adult ADHD may be an arduous task as it involved numerous challenges, such as a need for high index of suspicion to diagnose this medical condition. Many psychiatric disorders masquerade as ADHD and delayed the necessary assessment and proper treatment for the debilitating medical condition. Adult ADHD would also be misdiagnosed (or under diagnosed) due to the facts that this medical condition is being masked by his or her high level of intellectuality achievement...
May 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28492899/postmarket-safety-events-among-novel-therapeutics-approved-by-the-us-food-and-drug-administration-between-2001-and-2010
#16
Nicholas S Downing, Nilay D Shah, Jenerius A Aminawung, Alison M Pease, Jean-David Zeitoun, Harlan M Krumholz, Joseph S Ross
Importance: Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives: To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk...
May 9, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28492810/rimonabant-improves-metabolic-parameters-partially-attributed-to-restoration-of-high-voltage-activated-ca2-channels-in-skeletal-muscle-in-hfd-fed-mice
#17
B Chen, N Hu
Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising strategies for the treatment of obesity and other related metabolic disorders. Although CB1R inhibition may cause adverse psychiatric effects including depression and anxiety, the investigation of the role of peripheral CB1R on weight loss and related metabolic parameters are urgently needed. We first explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist, on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice...
May 4, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28488252/multiscale-modeling-in-the-clinic-diseases-of-the-brain-and-nervous-system
#18
REVIEW
William W Lytton, Jeff Arle, Georgiy Bobashev, Songbai Ji, Tara L Klassen, Vasilis Z Marmarelis, James Schwaber, Mohamed A Sherif, Terence D Sanger
Computational neuroscience is a field that traces its origins to the efforts of Hodgkin and Huxley, who pioneered quantitative analysis of electrical activity in the nervous system. While also continuing as an independent field, computational neuroscience has combined with computational systems biology, and neural multiscale modeling arose as one offshoot. This consolidation has added electrical, graphical, dynamical system, learning theory, artificial intelligence and neural network viewpoints with the microscale of cellular biology (neuronal and glial), mesoscales of vascular, immunological and neuronal networks, on up to macroscales of cognition and behavior...
May 9, 2017: Brain Informatics
https://www.readbyqxmd.com/read/28485726/gene-body-5-hydroxymethylation-is-associated-with-gene-expression-changes-in-the-prefrontal-cortex-of-depressed-individuals
#19
J A Gross, A Pacis, G G Chen, M Drupals, P-E Lutz, L B Barreiro, G Turecki
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19)...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28481571/examination-of-real-time-fluctuations-in-suicidal-ideation-and-its-risk-factors-results-from-two-ecological-momentary-assessment-studies
#20
Evan M Kleiman, Brianna J Turner, Szymon Fedor, Eleanor E Beale, Jeff C Huffman, Matthew K Nock
Two studies examined 2 important but previously unanswered questions about the experience of suicidal ideation: (a) How does suicidal ideation vary over short periods of time?, and (b) To what degree do risk factors for suicidal ideation vary over short periods and are such changes associated with changes in suicidal ideation? Participants in Study 1 were 54 adults who had attempted suicide in the previous year and completed 28 days of ecological momentary assessment (EMA; average of 2.51 assessments per day; 2,891 unique assessments)...
May 8, 2017: Journal of Abnormal Psychology
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