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Molecular Psychiatry

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https://www.readbyqxmd.com/read/29733868/investigation-of-belinostat-induced-genomic-instability-by-molecular-cytogenetic-analysis-and-pathway-focused-gene-expression-profiling
#1
S M Attia, M A Al-Hamamah, M R Alotaibi, G I Harisa, M M Attia, S F Ahmad, M A Ansari, A Nadeem, S A Bakheet
Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study...
May 4, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29687938/trait-and-state-biomarkers-for-psychiatric-disorders-importance-of-infrastructure-to-bridge-the-gap-between-basic-and-clinical-research-and-industry
#2
Yukiko Y Lema, Nao J Gamo, Kun Yang, Koko Ishizuka
To further improve clinical activities in psychiatry by early diagnosis and early intervention with novel mechanism-guided treatments, there is a great need for biomarkers that reflect "trait" and "state" in major mental disorders. Stable trait biomarkers would allow early diagnosis, prognosis, and hopefully early intervention in these disorders, while dynamic state markers that reflect symptomatic changes would help to develop treatments that target these molecular mechanisms. However, in the search for such biomarkers, and eventually translating them to the clinic and industry, challenges currently exist at multiple levels, from basic scientific understanding, patient sample collection, and sample and data management, to bridging the gap between basic and clinical research and industry...
April 24, 2018: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29626337/network-neuroscience-a-framework-for-developing-biomarkers-in-psychiatry
#3
David M Lydon-Staley, Danielle S Bassett
Psychiatric disorders are disturbances of cognitive and behavioral processes mediated by the brain. Emerging evidence suggests that accurate biomarkers for psychiatric disorders might benefit from incorporating information regarding multiple brain regions and their interactions with one another, rather than considering local perturbations in brain structure and function alone. Recent advances in the field of applied mathematics generally - and network science specifically - provide a language to capture the complexity of interacting brain regions, and the application of this language to fundamental questions in neuroscience forms the emerging field of network neuroscience...
April 7, 2018: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/29570969/tardive-dyskinesia-recognition-patient-assessment-and-differential-diagnosis
#4
Rakesh Jain, Christoph U Correll
Tardive dyskinesia (TD) is an involuntary movement disorder associated with antipsychotic treatment. Because of the serious and potentially irreversible nature of TD, accurate diagnosis is crucial. However, diagnosing TD can be challenging, since the subtle and often fluctuating symptoms can be easily mistaken for symptoms of mental illness or other side effects. Although the risk of developing TD in relation to treatment with second-generation antipsychotics is lower than that associated with first-generation antipsychotics, the risk still exists and may be greater than once believed...
March 20, 2018: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29532791/mechanisms-of-ketamine-action-as-an-antidepressant
#5
P Zanos, T D Gould
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine's widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine's antidepressant actions but lack its undesirable effects...
March 13, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29523295/molecular-hypotheses-to-explain-the-shared-pathways-and-underlying-pathobiological-causes-in-catatonia-and-in-catatonic-presentations-in-neuropsychiatric-disorders
#6
E M Peter-Ross
The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways)...
April 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29496143/considerations-for-optimal-use-of-postmortem-human-brains-for-molecular-psychiatry-lessons-from-schizophrenia
#7
Cynthia Shannon Weickert, Debora A Rothmond, Tertia D Purves-Tyson
Schizophrenia is a disabling disease impacting millions of people around the world, for which there is no known cure. Current antipsychotic treatments for schizophrenia mainly target psychotic symptoms, do little to ameliorate social or cognitive deficits, have side-effects that cause weight gain, and diabetes and 30% of people do not respond. Thus, better therapeutics for schizophrenia aimed at the route biologic changes are needed and discovering the underlying neurobiology is key to this quest. Postmortem brain studies provide the most direct and detailed way to determine the pathophysiology of schizophrenia...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29483673/deep-brain-stimulation-for-treatment-resistant-depression-an-integrative-review-of-preclinical-and-clinical-findings-and-translational-implications
#8
M P Dandekar, A J Fenoy, A F Carvalho, J C Soares, J Quevedo
Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD...
May 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29473292/polyphenolic-compounds-alter-stress-induced-patterns-of-global-dna-methylation-in-brain-and-blood
#9
Jennifer Blaze, Jun Wang, Lap Ho, Natalia Mendelev, Fatemeh Haghighi, Giulio Maria Pasinetti
SCOPE: Stress is a known contributor to various forms of disease in humans and animals, although mechanisms are still unknown. In animals, psychosocial stress-induced depression/anxiety phenotypes are coincidental with increased inflammation in both brain and blood. The authors recently showed that a novel treatment with a select bioactive polyphenol preparation promotes resilience to stress-mediated depression/anxiety phenotypes mice. Moreover, selective bioactive phenolic compounds within the polyphenol preparation are identified that are effective in mitigating the behavioral effects of bone marrow transplantation from stressed mice...
April 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29340519/evaluating-the-current-state-of-the-art-of-huntington-disease-research-a-scientometric-analysis
#10
REVIEW
L A Barboza, N C Ghisi
Huntington disease (HD) is an incurable neurodegenerative disorder caused by a dominant mutation on the 4th chromosome. We aim to present a scientometric analysis of the extant scientific undertakings devoted to better understanding HD. Therefore, a quantitative study was performed to examine the current state-of-the-art approaches that foster researchers' understandings of the current knowledge, research trends, and research gaps regarding this disorder. We performed literature searches of articles that were published up to September 2016 in the "ISI Web of Science™" (http://apps...
January 11, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29311665/hippocampal-dysfunction-in-the-pathophysiology-of-schizophrenia-a-selective-review-and-hypothesis-for-early-detection-and-intervention
#11
J A Lieberman, R R Girgis, G Brucato, H Moore, F Provenzano, L Kegeles, D Javitt, J Kantrowitz, M M Wall, C M Corcoran, S A Schobel, S A Small
Scientists have long sought to characterize the pathophysiologic basis of schizophrenia and develop biomarkers that could identify the illness. Extensive postmortem and in vivo neuroimaging research has described the early involvement of the hippocampus in the pathophysiology of schizophrenia. In this context, we have developed a hypothesis that describes the evolution of schizophrenia-from the premorbid through the prodromal stages to syndromal psychosis-and posits dysregulation of glutamate neurotransmission beginning in the CA1 region of the hippocampus as inducing attenuated psychotic symptoms and initiating the transition to syndromal psychosis...
January 9, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29310970/lithium-stress-and-resilience-in-bipolar-disorder-deciphering-this-key-homeostatic-synaptic-plasticity-regulator
#12
REVIEW
Rodrigo Machado-Vieira
BACKGROUND: Lithium is the lightest metal and the only mood stabilizer that has been used for over half a century for the treatment of bipolar disorder (BD). As a small ion, lithium is omnipresent, and consequently, its molecular mechanisms and targets are widespread. Currently, lithium is a crucial pharmacotherapy for the treatment of acute mood episodes, prophylactic therapy, and suicide prevention in BD. Besides, lithium blood level is the most widely used biomarker in clinical psychiatry...
June 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29295738/psychiatry-in-a-dish-stem-cells-and-brain-organoids-modeling-autism-spectrum-disorders
#13
REVIEW
Mirolyba Ilieva, Åsa Fex Svenningsen, Morten Thorsen, Tanja Maria Michel
Autism spectrum disorders are a group of pervasive neurodevelopmental conditions with heterogeneous etiology, characterized by deficits in social cognition, communication, and behavioral flexibility. Despite an increasing scientific effort to find the pathophysiological explanations for the disease, the neurobiological links remain unclear. A large amount of evidence suggests that pathological processes taking place in early embryonic neurodevelopment might be responsible for later manifestation of autistic symptoms...
April 1, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29258528/social-inequality-scientific-inequality-and-the-future-of-mental-illness
#14
REVIEW
Charles E Dean
BACKGROUND: Despite five decades of increasingly elegant studies aimed at advancing the pathophysiology and treatment of mental illness, the results have not met expectations. Diagnoses are still based on observation, the clinical history, and an outmoded diagnostic system that stresses the historic goal of disease specificity. Psychotropic drugs are still based on molecular targets developed decades ago, with no increase in efficacy. Numerous biomarkers have been proposed, but none have the requisite degree of sensitivity and specificity, and therefore have no usefulness in the clinic...
December 19, 2017: Philosophy, Ethics, and Humanities in Medicine: PEHM
https://www.readbyqxmd.com/read/29230023/pharmacogenetics-predictors-of-methylphenidate-efficacy-in-childhood-adhd
#15
N M Myer, J R Boland, S V Faraone
Stimulant medication has long been effective in treating attention-deficit/hyperactivity disorder (ADHD) and is currently the first-line pharmacological treatment for children. Both methylphenidate and amphetamine modulate extracellular catecholamine levels through interaction with dopaminergic, adrenergic and serotonergic system components; it is therefore likely that catecholaminergic molecular components influence the effects of ADHD treatment. Using meta-analysis, we sought to identify predictors of pharmacotherapy to further the clinical implementation of personalized medicine...
December 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29230022/trained-innate-immunity-a-salient-factor-in-the-pathogenesis-of-neuroimmune-psychiatric-disorders
#16
A P Salam, A Borsini, P A Zunszain
Historically, only cells of the adaptive immune system have been considered capable of retaining memory for infectious challenges. Recently, however, cells of the innate immune system have been shown to be capable of displaying long-term functional memory following a single immunostimulatory challenge, leading to enhanced production of proinflammatory molecules upon other subsequent, and temporally distant, immunostimulatory challenges. This effect has been termed 'trained innate immunity', and is underwritten by stable epigenetic changes in immune and metabolic pathways...
February 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29230021/markers-of-microglia-in-post-mortem-brain-samples-from-patients-with-alzheimer-s-disease-a-systematic-review
#17
REVIEW
K E Hopperton, D Mohammad, M O Trépanier, V Giuliano, R P Bazinet
Neuroinflammation is proposed as one of the mechanisms by which Alzheimer's disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction. Increases in the expression of markers of microglia, the main neuroinmmune cell, are widely reported in brains from patients with Alzheimer's disease, but the literature has not yet been systematically reviewed to determine whether this is a consistent pathological feature. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to 23 February 2017...
February 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203852/the-dynamics-of-stress-a-longitudinal-mri-study-of-rat-brain-structure-and-connectome
#18
R Magalhães, D A Barrière, A Novais, F Marques, P Marques, J Cerqueira, J C Sousa, A Cachia, F Boumezbeur, M Bottlaender, T M Jay, S Mériaux, N Sousa
Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203851/dynamic-landscape-of-the-local-translation-at-activated-synapses
#19
T M Khlebodarova, V V Kogai, E A Trifonova, V A Likhoshvai
The mammalian target of rapamycin (mTOR) signaling pathway is the central regulator of cap-dependent translation at the synapse. Disturbances in mTOR pathway have been associated with several neurological diseases, such as autism and epilepsy. RNA-binding protein FMRP, a negative regulator of translation initiation, is one of the key components of the local translation system. Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and dephosphorylation by PP2A phosphatase, respectively...
January 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203849/an-integrated-brain-behavior-model-for-working-memory
#20
D A Moser, G E Doucet, A Ing, D Dima, G Schumann, R M Bilder, S Frangou
Working memory (WM) is a central construct in cognitive neuroscience because it comprises mechanisms of active information maintenance and cognitive control that underpin most complex cognitive behavior. Individual variation in WM has been associated with multiple behavioral and health features including demographic characteristics, cognitive and physical traits and lifestyle choices. In this context, we used sparse canonical correlation analyses (sCCAs) to determine the covariation between brain imaging metrics of WM-network activation and connectivity and nonimaging measures relating to sensorimotor processing, affective and nonaffective cognition, mental health and personality, physical health and lifestyle choices derived from 823 healthy participants derived from the Human Connectome Project...
December 5, 2017: Molecular Psychiatry
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