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https://www.readbyqxmd.com/read/28436443/curcumol-allosterically-modulates-gaba-a-receptors-in-a-manner-distinct-from-benzodiazepines
#1
Yan-Mei Liu, Hui-Ran Fan, Jing Ding, Chen Huang, Shining Deng, Tailin Zhu, Tian-Le Xu, Wei-Hong Ge, Wei-Guang Li, Fei Li
Inhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28433511/design-synthesis-and-pharmacological-evaluation-of-4-azolyl-benzamide-derivatives-as-novel-gpr52-agonists
#2
Kazuyuki Tokumaru, Yoshiteru Ito, Izumi Nomura, Takashi Nakahata, Yuji Shimizu, Emi Kurimoto, Kazunobu Aoyama, Kazuyoshi Aso
G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (4u; half maximal effective concentration (EC50)=75nM, maximal response (Emax)=122%) starting from a high-throughput screening hit 3 (EC50=470nM, Emax=56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists...
April 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28431270/clinicians-conflicting-emotional-responses-to-high-suicide-risk-patients-association-with-short-term-suicide-behaviors-a-prospective-pilot-study
#3
Zimri S Yaseen, Igor I Galynker, Lisa J Cohen, Jessica Briggs
BACKGROUND: Clinician's emotional responses to patients have been recognized as potentially relating to treatment outcome, however they have received little attention in the literature on suicide risk. We examine the relationship between a novel targeted measure of clinicians' emotional responses to high-risk psychiatric inpatients and their short-term post-discharge suicide behavior. METHODS: First-year psychiatry residents' emotional responses to their patients were assessed anonymously with the novel self-report 'Therapist Response Questionnaire-Suicide Form' (TRQ-SF)...
April 6, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28427114/h-lifestyle-use-of-drugs-by-healthy-people-for-enhancing-cognition-creativity-motivation-and-pleasure
#4
REVIEW
L-S Camilla d'Angelo, George Savulich, Barbara J Sahakian
Today there is continued, and in some cases growing, availability of psychoactive substances, including treatments for mental health disorders such as cognitive enhancers, which can enhance or restore brain function, but also 'recreational' drugs such as novel psychoactive substances (NPS). The use of psychoactive drugs has both benefits and risks: whilst new drugs to treat cognitive symptoms in neuropsychiatric or neurodegenerative disorders could have great benefits for many patient groups, the increasing ease of accessibility to recreational NPS and the increasing lifestyle use of cognitive enhancers by healthy people means that the effective management of psychoactive substances will be an issue of increasing importance...
April 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28425495/the-biglen-gpr171-peptide-receptor-system-within-the-basolateral-amygdala-regulates-anxiety-like-behavior-and-contextual-fear-conditioning
#5
Erin N Bobeck, Ivone Gomes, Darlene Pena, Kirstie A Cummings, Roger L Clem, Mihaly Mezei, Lakshmi A Devi
Studies show that neuropeptide-receptor systems in the basolateral amygdala (BLA) play an important role in the pathology of anxiety and other mood disorders. Since GPR171, a recently deorphanized receptor for the abundant neuropeptide BigLEN, is expressed in the BLA, we investigated its role in fear and anxiety-like behaviors. To carry out these studies we identified small molecule ligands using a homology model of GPR171 to virtually screen a library of compounds. One of the hits, MS0021570_1, was identified as a GPR171 antagonist based on its ability to block (i) BigLEN-mediated activation of GPR171 in heterologous cells, (ii) BigLEN-mediated hyperpolarization of BLA pyramidal neurons, and (iii) feeding induced by DREADD-mediated activation of BigLEN containing AgRP neurons in the arcuate nucleus...
April 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28425121/role-of-the-dynorphin-kappa-opioid-receptor-system-in-the-motivational-effects-of-ethanol
#6
Rachel I Anderson, Howard C Becker
Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor (KOR) system contribute to various psychiatric disorders, including anxiety, depression, and addiction. More recently, this endogenous opioid system has received increased attention as a potential therapeutic target for treating alcohol use disorders. In this review, we provide an overview and synthesis of preclinical studies examining the influence of alcohol (ethanol) exposure on DYN/KOR expression and function, as well as studies examining the effects of DYN/KOR manipulation on ethanol's rewarding and aversive properties...
April 20, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28424797/magnetoencephalography-as-a-tool-in-psychiatric-research-current-status-and-perspective
#7
REVIEW
Peter J Uhlhaas, Peter Liddle, David E J Linden, Anna C Nobre, Krish D Singh, Joachim Gross
The application of neuroimaging to provide mechanistic insights into circuit dysfunctions in major psychiatric conditions and the development of biomarkers are core challenges in current psychiatric research. We propose that recent technological and analytic advances in magnetoencephalography (MEG), a technique that allows measurement of neuronal events directly and noninvasively with millisecond resolution, provides novel opportunities to address these fundamental questions. Because of its potential in delineating normal and abnormal brain dynamics, we propose that MEG provides a crucial tool to advance our understanding of pathophysiological mechanisms of major neuropsychiatric conditions, such as schizophrenia, autism spectrum disorders, and the dementias...
April 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/28424045/a-modified-mediterranean-dietary-intervention-for-adults-with-major-depression-dietary-protocol-and-feasibility-data-from-the-smiles-trial
#8
Rachelle S Opie, Adrienne O'Neil, Felice N Jacka, Josephine Pizzinga, Catherine Itsiopoulos
BACKGROUND: The SMILES trial was the first randomized controlled trial (RCT) explicitly designed to evaluate a dietary intervention, conducted by qualified dietitians, for reducing depressive symptomatology in adults with clinical depression. OBJECTIVES: Here we detail the development of the prescribed diet (modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive disorders (MDDs) that was designed specifically for the SMILES trial. We also present data demonstrating the extent to which this intervention achieved improvements in diet quality...
April 19, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28422133/gene-set-analysis-shows-association-between-fmrp-targets-and-autism-spectrum-disorder
#9
Arija Jansen, Gwen C Dieleman, August B Smit, Matthijs Verhage, Frank C Verhulst, Tinca J C Polderman, Danielle Posthuma
Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding biological mechanisms are largely unknown. Our objective is to investigate the contribution of common genetic variation to biological pathways functionally involved in ASD. We conducted gene-set analyses to identify ASD-associated functional biological pathways using the statistical tools MAGMA and INRICH...
April 19, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28421479/understanding-medical-students-experience-with-stress-and-its-related-constructs-a-focus-group-study-from-singapore
#10
Julia Farquhar, Desiree Lie, Angelique Chan, Mandy Ow, Arpana Vidyarthi
OBJECTIVE: In order to protect medical students from burnout and its untoward psychiatric effects, it is imperative to understand their stress, burnout, coping, and resilience experiences. This study aimed to derive collective definitions from the medical student perspective, to identify common themes of students' experiences, and to distinguish pre-clinical and clinical year students' experiences relating to these four constructs. METHODS: The authors conducted focus groups of medical students in Singapore across 4 years using a semi-structured question guide...
April 18, 2017: Academic Psychiatry
https://www.readbyqxmd.com/read/28410113/watch-dog-detecting-self-harming-activities-from-wrist-worn-accelerometers
#11
Pratool Bharti, Anurag Panwar, Ganesh Gopalakrishna, Sriram Chellappan
In a 2012 survey, in the United States alone, there were more than 35; 000 reported suicides with approximately 1; 800 of being psychiatric inpatients. Recent CDC (Centers for Disease Control and Prevention) reports indicate an upward trend in these numbers. In psychiatric facilities, staff perform intermittent or continuous observation of patients manually in order to prevent such tragedies, but studies show that they are insufficient, and also consume staff time and resources. In this paper, we present the Watch-Dog system, to address the problem of detecting self-harming activities when attempted by in-patients in clinical settings...
April 7, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#12
REVIEW
Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
https://www.readbyqxmd.com/read/28408831/modulation-of-the-activity-of-n-methyl-d-aspartate-receptors-as-a-novel-treatment-option-for-depression-current-clinical-evidence-and-therapeutic-potential-of-rapastinel-glyx-13
#13
REVIEW
Andrei-Nicolae Vasilescu, Nina Schweinfurth, Stefan Borgwardt, Peter Gass, Undine E Lang, Dragos Inta, Sarah Eckart
Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28408774/historical-analyses-of-disordered-handwriting-perspectives-on-early-20th-century-material-from-a-german-psychiatric-hospital
#14
Markus Schiegg, Deborah Thorpe
Handwritten texts carry significant information, extending beyond the meaning of their words. Modern neurology, for example, benefits from the interpretation of the graphic features of writing and drawing for the diagnosis and monitoring of diseases and disorders. This article examines how handwriting analysis can be used, and has been used historically, as a methodological tool for the assessment of medical conditions and how this enhances our understanding of historical contexts of writing. We analyze handwritten material, writing tests and letters, from patients in an early 20th-century psychiatric hospital in southern Germany (Irsee/Kaufbeuren)...
January 2017: Writ Commun
https://www.readbyqxmd.com/read/28405619/role-of-adenylyl-cyclase-6-in-the-development-of-lithium-induced-nephrogenic-diabetes-insipidus
#15
Søren Brandt Poulsen, Tina Bøgelund Kristensen, Heddwen L Brooks, Donald E Kohan, Timo Rieg, Robert A Fenton
Psychiatric patients treated with lithium (Li(+)) may develop nephrogenic diabetes insipidus (NDI). Although the etiology of Li(+)-induced NDI (Li-NDI) is poorly understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in the kidney collecting ducts. A mechanism postulated for this is that Li(+) inhibits adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2 abundance, and less membrane targeting. We hypothesized that Li-NDI would not develop in mice lacking AC6. Whole-body AC6 knockout (AC6(-/-)) mice and potentially novel connecting tubule/principal cell-specific AC6 knockout (AC6(loxloxCre)) mice had approximately 50% lower urine osmolality and doubled water intake under baseline conditions compared with controls...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28402427/bdnf-overexpression-prevents-cognitive-deficit-elicited-by-adolescent-cannabis-exposure-and-host-susceptibility-interaction
#16
Hadar Segal-Gavish, Neta Gazit, Yael Barhum, Tali Ben-Zur, Michal Taler, Shay Henry Hornfeld, Irit Gil-Ad, Abraham Weizman, Inna Slutsky, Minae Niwa, Atsushi Kamiya, Akira Sawa, Daniel Offen, Ran Barzilay
Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations...
April 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28402333/maoa-a-novel-decision-maker-of-apoptosis-and-autophagy-in-hormone-refractory-neuroendocrine-prostate-cancer-cells
#17
Yi-Cheng Lin, Yi-Ting Chang, Mel Campbell, Tzu-Ping Lin, Chin-Chen Pan, Hsin-Chen Lee, Jean C Shih, Pei-Ching Chang
Autophagy and apoptosis are two well-controlled mechanisms regulating cell fate. An understanding of decision-making between these two pathways is in its infancy. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that is well-known in psychiatric research. Emerging reports showed that overexpression MAOA is associated with prostate cancer (PCa). Here, we show that MAOA is involved in mediating neuroendocrine differentiation of PCa cells, a feature associated with hormone-refractory PCa (HRPC), a lethal type of disease...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401046/functional-neuroanatomy-in-panic-disorder-status-quo-of-the-research
#18
Thomas Sobanski, Gerd Wagner
AIM: To provide an overview of the current research in the functional neuroanatomy of panic disorder. METHODS: Panic disorder (PD) is a frequent psychiatric disease. Gorman et al (1989; 2000) proposed a comprehensive neuroanatomical model of PD, which suggested that fear- and anxiety-related responses are mediated by a so-called "fear network" which is centered in the amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other brainstem sites...
March 22, 2017: World Journal of Psychiatry
https://www.readbyqxmd.com/read/28398357/a-resource-for-assessing-information-processing-in-the-developing-brain-using-eeg-and-eye-tracking
#19
Nicolas Langer, Erica J Ho, Lindsay M Alexander, Helen Y Xu, Renee K Jozanovic, Simon Henin, Agustin Petroni, Samantha Cohen, Enitan T Marcelle, Lucas C Parra, Michael P Milham, Simon P Kelly
We present a dataset combining electrophysiology and eye tracking intended as a resource for the investigation of information processing in the developing brain. The dataset includes high-density task-based and task-free EEG, eye tracking, and cognitive and behavioral data collected from 126 individuals (ages: 6-44). The task battery spans both the simple/complex and passive/active dimensions to cover a range of approaches prevalent in modern cognitive neuroscience. The active task paradigms facilitate principled deconstruction of core components of task performance in the developing brain, whereas the passive paradigms permit the examination of intrinsic functional network activity during varying amounts of external stimulation...
April 11, 2017: Scientific Data
https://www.readbyqxmd.com/read/28397115/neural-substrates-of-depression-and-resilience
#20
REVIEW
Ming-Hu Han, Eric J Nestler
There is an urgent need for more effective medications to treat major depressive disorder, as fewer than half of depressed patients achieve full remission and many are not responsive with currently available antidepressant medications or psychotherapy. It is known that prolonged stressful events are an important risk factor for major depressive disorder. However, there are prominent individual variations in response to stress: a relatively small proportion of people (10-20%) experiencing prolonged stress develop stress-related psychiatric disorders, including depression (susceptibility to stress), whereas most stress-exposed individuals maintain normal psychological functioning (resilience to stress)...
April 10, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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