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Molecular Psychiatry

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https://www.readbyqxmd.com/read/29340519/evaluating-the-current-state-of-the-art-of-huntington-disease-research-a-scientometric-analysis
#1
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
#2
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
#3
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...
December 22, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29295738/psychiatry-in-a-dish-stem-cells-and-brain-organoids-modeling-autism-spectrum-disorders
#4
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...
November 16, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29258528/social-inequality-scientific-inequality-and-the-future-of-mental-illness
#5
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
#6
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
#7
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...
December 12, 2017: 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
#8
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...
December 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203852/the-dynamics-of-stress-a-longitudinal-mri-study-of-rat-brain-structure-and-connectome
#9
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
#10
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...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203849/an-integrated-brain-behavior-model-for-working-memory
#11
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
https://www.readbyqxmd.com/read/29203848/bdnf-release-and-signaling-are-required-for-the-antidepressant-actions-of-glyx-13
#12
T Kato, M V Fogaça, S Deyama, X-Y Li, K Fukumoto, R S Duman
Conventional antidepressant medications, which act on monoaminergic systems, display significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that acts as an N-methyl-d-aspartate (NMDA) modulator with glycine-like partial agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces rapid antidepressant actions in depressed patients and in preclinical rodent models. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been characterized...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203847/reconceptualization-of-translocator-protein-as-a-biomarker-of-neuroinflammation-in-psychiatry
#13
T Notter, J M Coughlin, A Sawa, U Meyer
A great deal of interest in psychiatric research is currently centered upon the pathogenic role of inflammatory processes. Positron emission tomography (PET) using radiolabeled ligands selective for the 18 kDa translocator protein (TSPO) has become the most widely used technique to assess putative neuroimmune abnormalities in vivo. Originally used to detect discrete neurotoxic damages, TSPO has generally turned into a biomarker of 'neuroinflammation' or 'microglial activation'. Psychiatric research has mostly accepted these denotations of TSPO, even if they may be inadequate and misleading under many pathological conditions...
January 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29180675/protein-kinase-m%C3%AE-in-medial-prefrontal-cortex-mediates-depressive-like-behavior-and-antidepressant-response
#14
W Yan, J-F Liu, Y Han, W Zhang, Y-X Luo, Y-X Xue, W-L Zhu, C Yang, W-H Chen, H-L Guo, Y-N Ma, K Yuan, J-S Wang, J Shi, L Lu
Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness...
November 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29180674/why-is-there-selective-subcortical-vulnerability-in-adhd-clues-from-postmortem-brain-gene-expression-data
#15
J L Hess, G C Akutagava-Martins, J D Patak, S J Glatt, S V Faraone
Sub-cortical volumetric differences were associated with attention-deficit/hyperactivity disorder (ADHD) in a recent multi-site, mega-analysis of 1713 ADHD persons and 1529 controls. As there was a wide range of effect sizes among the sub-cortical volumes, it is possible that selective neuronal vulnerability has a role in these volumetric losses. To address this possibility, we used data from Allen Brain Atlas to investigate variability in gene expression profiles between subcortical regions of typically developing brains...
November 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29180673/calhm2-governs-astrocytic-atp-releasing-in-the-development-of-depression-like-behaviors
#16
M Jun, Q Xiaolong, Y Chaojuan, P Ruiyuan, W Shukun, W Junbing, H Li, C Hong, C Jinbo, W Rong, L Yajin, M Lanqun, W Fengchao, W Zhiying, A Jianxiong, W Yun, Z Xia, Z Chen, Y Zengqiang
Extracellular ATP is a widespread cell-to-cell signaling molecule in the brain, where it functions as a neuromodulator by activating glia and neurons. Although ATP exerts multiple effects on synaptic plasticity and neuro-glia interactions, as well as in mood disorders, the source and regulation of ATP release remain to be elaborated. Here, we define Calhm2 as an ATP-releasing channel protein based on in vitro and in vivo models. Conventional knockout and conditional astrocyte knockout of Calhm2 both lead to significantly reduced ATP concentrations, loss of hippocampal spine number, neural dysfunction and depression-like behaviors in mice, which can be significantly rescued by ATP replenishment...
November 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29180672/the-thalamic-reticular-nucleus-in-schizophrenia-and-bipolar-disorder-role-of-parvalbumin-expressing-neuron-networks-and-oxidative-stress
#17
P Steullet, J-H Cabungcal, S A Bukhari, M I Ardelt, H Pantazopoulos, F Hamati, T E Salt, M Cuenod, Kim Q Do, S Berretta
Growing evidence points to a disruption of cortico-thalamo-cortical circuits in schizophrenia (SZ) and bipolar disorder (BD). Clues for a specific involvement of the thalamic reticular nucleus (TRN) come from its unique neuronal characteristics and neural connectivity, allowing it to shape the thalamo-cortical information flow. A direct involvement of the TRN in SZ and BD has not been tested thus far. We used a combination of human postmortem and rodent studies to test the hypothesis that neurons expressing parvalbumin (PV neurons), a main TRN neuronal population, and associated Wisteria floribunda agglutinin-labeled perineuronal nets (WFA/PNNs) are altered in SZ and BD, and that these changes may occur early in the course of the disease as a consequence of oxidative stress...
November 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158585/child-abuse-associates-with-an-imbalance-of-oligodendrocyte-lineage-cells-in-ventromedial-prefrontal-white-matter
#18
A Tanti, J J Kim, M Wakid, M-A Davoli, G Turecki, N Mechawar
Child abuse (CA) is a major risk factor for depression, and strongly associates with suicidal behavior during adulthood. Neuroimaging studies have reported widespread changes in white matter integrity and brain connectivity in subjects with a history of CA. Although such observations could reflect changes in myelin and oligodendrocyte function, their cellular underpinnings have never been addressed. Using postmortem brain samples from depressed suicides with or without history of CA and matched controls (18 per group), we aimed to characterize the effects of CA on oligodendrocyte-lineage (OL) cells in the ventromedial prefrontal white matter...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#19
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158583/patient-derived-ipscs-show-premature-neural-differentiation-and-neuron-type-specific-phenotypes-relevant-to-neurodevelopment
#20
E Yeh, D Q Dao, Z Y Wu, S M Kandalam, F M Camacho, C Tom, W Zhang, R Krencik, K A Rauen, E M Ullian, L A Weiss
Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAF(Q257R), the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation...
November 21, 2017: Molecular Psychiatry
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