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https://www.readbyqxmd.com/read/28723415/pharmacology-of-human-trace-amine-associated-receptors-therapeutic-opportunities-and-challenges
#1
REVIEW
Mark D Berry, Raul R Gainetdinov, Marius C Hoener, Mohammed Shahid
The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic. Despite these challenges the last 5 years have seen considerable advances, in particular with respect to TAAR1, which appears to function as an endogenous rheostat, maintaining central neurotransmission within defined physiological limits, in part through receptor heterodimerization yielding biased signaling outputs...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28723348/central-serotonin-attenuates-lps-induced-systemic-inflammation
#2
Clarissa M D Mota, Caroline Rodrigues-Santos, Rodrigo A R Fernández, Ruither O G Carolino, José Antunes-Rodrigues, Janete A Anselmo-Franci, Luiz G S Branco
Serotonin (5-HT) is a neuromodulator involved in several central-mediated mechanisms, such as endocrine processes, behavior, and sleep. Dysfunction of the serotonergic system is mainly linked to psychiatric disorders, but emerging evidence suggests that immune system activation may also alter brain 5-HT signaling. However, whether central 5-HT modulates systemic inflammation (SI) remains unknown. For this purpose, male Wistar rats (280-350 g, 8-9 weeks) were submitted to the experimental protocols beginning between 9 and 10 AM with the performance of injections...
July 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28719227/simvastatin-as-an-adjunctive-therapy-to-risperidone-in-treatment-of-autism-a-randomized-double-blind-placebo-controlled-clinical-trial
#3
Ehsan Moazen-Zadeh, Fatemeh Shirzad, Mohammad-Ali Karkhaneh-Yousefi, Rasoul Khezri, Mohammad-Reza Mohammadi, Shahin Akhondzadeh
OBJECTIVES: Providing novel treatments for autism has been a subject of long-standing research. Based on etiopathological findings, we aim at assessing potential therapeutic effects of statins, here simvastatin, on autism symptoms for the first time. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group 10-week clinical trial, 70 drug-free children aged 4 to 12 years old with diagnosis of autistic disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, were equally randomized to receive either simvastatin (20-40 mg/day) or placebo as an adjunct to risperidone (1-2 mg/day) whereas administration of both drugs was started simultaneously from baseline...
July 18, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28716445/feeding-systems-and-the-gut-microbiome-gut-brain-interactions-with-relevance-to-psychiatric-conditions
#4
REVIEW
Brittany L Mason
BACKGROUND: Physical and mental health is dependent on the environment, and feeding is a prime example of this environmental exchange. While the hypothalamus controls both feeding behavior and the stress response, the integration of the neural control centers and the peripheral gut allows for disruption in the gastrointestinal systems and dysfunctional communication to the brain. OBJECTIVE: The purpose of this review is to familiarize clinicians with the physiology controlling feeding behavior and its implications for psychiatric conditions, such as anorexia nervosa and depression...
June 8, 2017: Psychosomatics
https://www.readbyqxmd.com/read/28713685/understanding-the-pathophysiology-of-postpartum-psychosis-challenges-and-new-approaches
#5
REVIEW
William Davies
Postpartum psychosis is a severe psychiatric condition which affects 1-2 of every 1000 mothers shortly after childbirth. Whilst there is convincing evidence that the condition is precipitated by a complex combination of biological and environmental factors, as yet the pathophysiological mechanisms remain extremely poorly defined. Here, I critically review approaches that have been, or are being, employed to identify and characterise such mechanisms; I also review a recent animal model approach, and describe a novel biological risk model that it suggests...
June 22, 2017: World Journal of Psychiatry
https://www.readbyqxmd.com/read/28713243/synaptic-interactome-mining-reveals-p140cap-as-a-new-hub-for-psd-proteins-involved-in-psychiatric-and-neurological-disorders
#6
Annalisa Alfieri, Oksana Sorokina, Annie Adrait, Costanza Angelini, Isabella Russo, Alessandro Morellato, Michela Matteoli, Elisabetta Menna, Elisabetta Boeri Erba, Colin McLean, J Douglas Armstrong, Ugo Ala, Joseph D Buxbaum, Alfredo Brusco, Yohann Couté, Silvia De Rubeis, Emilia Turco, Paola Defilippi
Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28711512/seasonality-in-affective-disorders
#7
REVIEW
Anna Wirz-Justice
Humans retain neurobiological responses to circadian day-night cycles and seasonal changes in daylength in spite of a life-style usually independent of dawn-dusk signals. Seasonality has been documented in many functions, from mood to hormones to gene expression. Research on seasonal affective disorder initiated the first use of timed bright light as therapy, a treatment since extended to non-seasonal major depression and sleep-wake cycle disturbances in many psychiatric and medical illnesses. The growing recognition that sufficient light is important for psychological and somatic well-being is leading to the development of novel lighting solutions in architecture as well as focus on a more conscious exposure to natural daylight...
July 12, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28699794/valbenazine-for-the-treatment-of-tardive-dyskinesia
#8
Lauren C Seeberger, Robert A Hauser
Tardive dyskinesia (Td) is a hyperkinetic movement disorder that may result from treatment with antipsychotics or other dopamine receptor blocking agents. Underlying pathophysiology is incompletely understood but since the 1970s dopamine depleting agents have been used to reduce involuntary movements. The search for safe, effective treatments for Td is ongoing. Valbenazine, a novel VMAT2 inhibitor, has recently been FDA approved for treatment of Td. Areas Covered: An overview of Td, unmet medical needs and current treatment guidelines are presented...
July 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28699694/the-epigenomics-of-schizophrenia-in-the-mouse
#9
REVIEW
Behnam Javidfar, Royce Park, Bibi S Kassim, Lucy K Bicks, Schahram Akbarian
Large-scale consortia including the Psychiatric Genomics Consortium, the Common Minds Consortium, BrainSeq and PsychENCODE, and many other studies taken together provide increasingly detailed insights into the genetic and epigenetic risk architectures of schizophrenia (SCZ) and offer vast amounts of molecular information, but with largely unexplored therapeutic potential. Here we discuss how epigenomic studies in human brain could guide animal work to test the impact of disease-associated alterations in chromatin structure and function on cognition and behavior...
July 12, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28696950/the-role-of-stigma-and-denormalization-in-suicide-prevention-laws-in-east-asia-a-sociocultural-historical-and-ethical-perspective
#10
Justin A Chen, Andrew Courtwright, Kevin Chien-Chang Wu
In many Western countries, the criminalization and stigmatization of suicide has given way to a biomedical approach aimed at destigmatizing suicide and treating underlying mental illness. By contrast, in many East Asian countries, suicide has never historically been criminalized or stigmatized. High rates of suicide in Japan, South Korea, and Taiwan have recently led policy makers in those countries to pursue innovative suicide-prevention strategies. The intentional denormalization of harmful behaviors has been discussed in the public health and ethics literatures, particularly with regard to smoking cessation, and could represent a novel mechanism for preventing suicides in East Asia...
July 11, 2017: Harvard Review of Psychiatry
https://www.readbyqxmd.com/read/28694195/hemoglobins-emerging-roles-in-mental-disorders-metabolical-genetical-and-immunological-aspects
#11
REVIEW
Meric A Altinoz, Bahri Ince
Hemoglobin (Hb) expression in the central nervous system is recently shown. Cooccurences of mental disorders (mainly bipolar disorder (BD) and tic disorders) with β- or α-thalassemia trait or erythrocytosis were witnessed, which may be due to peripheral or central hypoxia/hyperoxia or haplotypal gene interactions. β-Globin genes reside at 11p15.5 close to tyrosine hydroxylase, dopamine receptor DRD4 and Brain Derived Neurotrophic Factor, which involve in psychiatric diseases. α-Globin genes reside at 16p13...
July 8, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28694114/epigenetic-dysregulation-of-protocadherins-in-human-disease
#12
REVIEW
Nady El Hajj, Marcus Dittrich, Thomas Haaf
Protocadherins (Pcdhs) are a group of cell-cell adhesion molecules that are highly expressed in the nervous system and have a major function in dendrite development and neural circuit formation. However, the role protocadherins play in human health and disease remains unclear. Several recent studies have associated epigenetic dysregulation of protocadherins with possible implications for disease pathogenesis. In this review, we briefly recap the various epigenetic mechanisms regulating protocadherin genes, particularly the clustered Pcdhs...
July 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28689852/development-of-an-integrated-cognitive-behavioral-therapy-for-anxiety-and-opioid-use-disorder-study-protocol-and-methods
#13
R Kathryn McHugh, Victoria R Votaw, David H Barlow, Garrett M Fitzmaurice, Shelly F Greenfield, Roger D Weiss
Opioid use disorder is a highly disabling psychiatric disorder, and is associated with both significant functional disruption and risk for negative health outcomes such as infectious disease and fatal overdose. Even among those who receive evidence-based pharmacotherapy for opioid use disorder, many drop out of treatment or relapse, highlighting the importance of novel treatment strategies for this population. Over 60% of those with opioid use disorder also meet diagnostic criteria for an anxiety disorder; however, efficacious treatments for this common co-occurrence have not be established...
July 8, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28687074/strength-of-functional-signature-correlates-with-effect-size-in-autism
#14
Sara Ballouz, Jesse Gillis
BACKGROUND: Disagreements over genetic signatures associated with disease have been particularly prominent in the field of psychiatric genetics, creating a sharp divide between disease burdens attributed to common and rare variation, with study designs independently targeting each. Meta-analysis within each of these study designs is routine, whether using raw data or summary statistics, but combining results across study designs is atypical. However, tests of functional convergence are used across all study designs, where candidate gene sets are assessed for overlaps with previously known properties...
July 7, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28686333/ehealth-provides-a-novel-opportunity-to-exploit-the-advantages-of-the-nordic-countries-in-psychiatric-genetic-research-building-on-the-public-health-care-system-biobanks-and-registries
#15
REVIEW
Ole A Andreassen
Nordic countries have played an important role in the recent progress in psychiatric genetics, both with large well-characterized samples and expertise. The Nordic countries have research advantages due to the organization of their societies, including system of personal identifiers, national health registries with information about diseases, treatment and prescriptions, and a public health system with geographical catchment areas. For psychiatric genetic research, the large biobanks and population surveys are a unique added value...
July 7, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28676310/an-investigation-into-the-effects-and-prognostic-factors-of-cognitive-decline-following-subthalamic-nucleus-stimulation-in-patients-with-parkinson-s-disease
#16
Taro Nimura, Ken-Ichi Nagamatsu, Tadashi Ando, Arifumi Matsumoto, Kinya Hisanaga, Teiji Tominaga
We retrospectively investigated the effects of subthalamic nucleus stimulation (STN-DBS) on new postoperative onset of cognitive decline and prognostic factors for advanced Parkinson's disease (PD). We studied 39 PD patients who had received bilateral STN-DBS. Clinical symptoms, cognitive function, psychiatric function, and health-related quality of life (HRQOL) were assessed before and six months after surgery. Based on the results of neuropsychological examinations six months after the surgery, the subjects were divided into those with and those without cognitive decline...
July 1, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28672848/mechanism-exploration-of-arylpiperazine-derivatives-targeting-the-5-ht2a-receptor-by-in-silico-methods
#17
Feng Lin, Feng Li, Chao Wang, Jinghui Wang, Yinfeng Yang, Ling Yang, Yan Li
As a G-protein coupled receptor, the 5-hydroxytryptamine 2A (5-HT2A) receptor is known for its critical role in the cognitive, behavioural and physiological functions, and thus is a primary molecular target to treat psychiatric diseases, including especially depression. With purpose to explore the structural traits affecting the inhibitory activity, currently a dataset of 109 arylpiperazine derivatives as promising 5-HT2A antagonists was built, based on which the ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) study by using both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches was carried out...
June 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28671614/endocannabinod-signal-dysregulation-in-autism-spectrum-disorders-a-correlation-link-between-inflammatory-state-and-neuro-immune-alterations
#18
REVIEW
Anna Lisa Brigida, Stephen Schultz, Mariana Cascone, Nicola Antonucci, Dario Siniscalco
Several studies highlight a key involvement of endocannabinoid (EC) system in autism pathophysiology. The EC system is a complex network of lipid signaling pathways comprised of arachidonic acid-derived compounds (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. In addition to autism, the EC system is also involved in several other psychiatric disorders (i.e., anxiety, major depression, bipolar disorder and schizophrenia)...
July 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28670349/epigenetic-mechanisms-during-ageing-and-neurogenesis-as-novel-therapeutic-avenues-in-human-brain-disorders
#19
REVIEW
Raúl Delgado-Morales, Roberto Carlos Agís-Balboa, Manel Esteller, María Berdasco
Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28668671/deutetrabenazine-for-treatment-of-involuntary-movements-in-patients-with-tardive-dyskinesia-aim-td-a-double-blind-randomised-placebo-controlled-phase-3-trial
#20
Karen E Anderson, David Stamler, Mat D Davis, Stewart A Factor, Robert A Hauser, Jouko Isojärvi, L Fredrik Jarskog, Joohi Jimenez-Shahed, Rajeev Kumar, Joseph P McEvoy, Stanislaw Ochudlo, William G Ondo, Hubert H Fernandez
BACKGROUND: Tardive dyskinesia results from exposure to dopamine receptor antagonists, such as typical and atypical antipsychotics. If clinically appropriate, clinicians often manage this disorder by lowering the dose of, or discontinuing, the causative drug. There is a significant unmet need for a treatment option that does not disrupt treatment regimens for underlying psychiatric illnesses. We aimed to assess the efficacy, safety, and tolerability of fixed doses of deutetrabenazine-a novel vesicular monoamine transporter-2 inhibitor-in patients with tardive dyskinesia...
June 28, 2017: Lancet Psychiatry
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