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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28289284/the-schizophrenia-risk-gene-znf804a-clinical-associations-biological-mechanisms-and-neuronal-functions
#1
REVIEW
H Chang, X Xiao, M Li
ZNF804A (zinc-finger protein 804A) has been recognized as a schizophrenia risk gene across multiple world populations. Its intronic single-nucleotide polymorphism (SNP) rs1344706 is among one of the strongest susceptibility variants that have achieved genome-wide significance in genome-wide association studies (GWAS) for schizophrenia and has been widely and intensively studied. To elucidate the biological mechanisms underlying the genetic risk conferred by rs1344706, we retrospectively analyzed the progresses in brain gene expression quantitative trait loci (eQTL) analyses, ZNF804A-induced pathway alterations in neural cells and changes in synaptic phenotypes associated with ZNF804A expression...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289283/the-dopamine-hypothesis-of-bipolar-affective-disorder-the-state-of-the-art-and-implications-for-treatment
#2
REVIEW
A H Ashok, T R Marques, S Jauhar, M M Nour, G M Goodwin, A H Young, O D Howes
Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine function in bipolar disorder...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289282/the-schizophrenia-and-autism-associated-gene-transcription-factor-4-regulates-the-columnar-distribution-of-layer-2-3-prefrontal-pyramidal-neurons-in-an-activity-dependent-manner
#3
S C Page, G R Hamersky, R A Gallo, M D Rannals, N E Calcaterra, M N Campbell, B Mayfield, A Briley, B N Phan, A E Jaffe, B J Maher
Disruption of the laminar and columnar organization of the brain is implicated in several psychiatric disorders. Here, we show in utero gain-of-function of the psychiatric risk gene transcription factor 4 (TCF4) severely disrupts the columnar organization of medial prefrontal cortex (mPFC) in a transcription- and activity-dependent manner. This morphological phenotype was rescued by co-expression of TCF4 plus calmodulin in a calcium-dependent manner and by dampening neuronal excitability through co-expression of an inwardly rectifying potassium channel (Kir2...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289281/oxytocin-by-intranasal-and-intravenous-routes-reaches-the-cerebrospinal-fluid-in-rhesus-macaques-determination-using-a-novel-oxytocin-assay
#4
M R Lee, K B Scheidweiler, X X Diao, F Akhlaghi, A Cummins, M A Huestis, L Leggio, B B Averbeck
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289280/biochemical-physiological-and-clinical-effects-of-l-methylfolate-in-schizophrenia-a-randomized-controlled-trial
#5
J L Roffman, L J Petruzzi, A S Tanner, H E Brown, H Eryilmaz, N F Ho, M Giegold, N J Silverstein, T Bottiglieri, D S Manoach, J W Smoller, D C Henderson, D C Goff
Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289279/next-gen-sequencing-identifies-non-coding-variation-disrupting-mirna-binding-sites-in-neurological-disorders
#6
P Devanna, X S Chen, J Ho, D Gajewski, S D Smith, A Gialluisi, C Francks, S E Fisher, D F Newbury, S C Vernes
Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289278/cafeteria-diet-and-probiotic-therapy-cross-talk-among-memory-neuroplasticity-serotonin-receptors-and-gut-microbiota-in-the-rat
#7
J E Beilharz, N O Kaakoush, J Maniam, M J Morris
The western diet is known to have detrimental effects on cognition and the gut microbiota, but few studies have investigated how these may be related. Here, we examined whether a probiotic could prevent diet-induced memory deficits. Rats were pre-exposed to vehicle, low or high doses of VSL#3 for 2 weeks before half were switched from chow to a cafeteria diet (Caf) for 25 days; VSL#3 treatment continued until death. High-dose VSL#3 prevented the diet-induced memory deficits on the hippocampal-dependent place task, but the probiotic caused deficits on the perirhinal-dependent object task, irrespective of diet or dose...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289277/csf-gaba-is-reduced-in-first-episode-psychosis-and-associates-to-symptom-severity
#8
F Orhan, H Fatouros-Bergman, M Goiny, A Malmqvist, F Piehl, S Cervenka, K Collste, P Victorsson, C M Sellgren, L Flyckt, S Erhardt, G Engberg
Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289276/david-skae-and-his-nineteenth-century-etiologic-psychiatric-diagnostic-system-looking-forward-by-looking-back
#9
K S Kendler
The Kraepelinian syndromal approach to diagnosis taken by DSM-III and its successors, which defines disorders by their clinical phenomenon, has come under rising criticism with increasing calls for an etiologically based nosology. The relative virtues of a syndromal versus etiologic psychiatric nosology have actually been debated within our field for a long time. To deepen and historically contextualize our current discussion, I review in detail the proposal for etiologic diagnostic systems for insanity by David Skae (1814-1873)...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289275/epigenetic-programming-by-stress-and-glucocorticoids-along-the-human-lifespan
#10
A S Zannas, G P Chrousos
Psychosocial stress triggers a set of behavioral, neural, hormonal, and molecular responses that can be a driving force for survival when adaptive and time-limited, but may also contribute to a host of disease states if dysregulated or chronic. The beneficial or detrimental effects of stress are largely mediated by the hypothalamic-pituitary axis, a highly conserved neurohormonal cascade that culminates in systemic secretion of glucocorticoids. Glucocorticoids activate the glucocorticoid receptor, a ubiquitous nuclear receptor that not only causes widespread changes in transcriptional programs, but also induces lasting epigenetic modifications in many target tissues...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28283186/imaging-genetics-and-genomics-in-psychiatry-a-critical-review-of-progress-and-potential
#11
REVIEW
Ryan Bogdan, Betty Jo Salmeron, Caitlin E Carey, Arpana Agrawal, Vince D Calhoun, Hugh Garavan, Ahmad R Hariri, Andreas Heinz, Matthew N Hill, Andrew Holmes, Ned H Kalin, David Goldman
Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges, including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity...
January 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28282074/-epigenetics-2-0-the-multiple-faces-of-the-genome
#12
Marcelo Rubinstein
Epigenetics is the branch of genetics that studies the dynamic relationship between stable genotypes and varying phenotypes. To this end, epigenetics aims to discover the molecular mechanisms that explain how different nutrients and hormones, environmental changes, and emotional, social and cognitive experiences modify gene expression and behaviors, even permanently so. Psychiatry has learned that diseases with strong genetic predisposition, such as schizophrenia, show a concordance of around 50% between monozygotic twins, thus evidencing the importance of the genetic background and the presence of environmental variables that stimulate or block phenotypic development...
September 2016: Vertex: Revista Argentina de Psiquiatriá
https://www.readbyqxmd.com/read/28265121/brain-structural-and-functional-signatures-of-impulsive-compulsive-behaviours-in-parkinson-s-disease
#13
F Imperiale, F Agosta, E Canu, V Markovic, A Inuggi, M Jecmenica-Lukic, A Tomic, M Copetti, S Basaia, V S Kostic, M Filippi
This study assessed brain structural and functional alterations in patients with Parkinson's disease and impulsive-compulsive behaviours (PD-ICB) compared with controls and PD no-ICB cases. Eighty-five PD patients (35 PD-ICB) and 50 controls were recruited. All subjects underwent three-dimensional T1-weighted, diffusion tensor (DT), and resting state functional magnetic resonance imaging (RS fMRI). We assessed cortical thickness with surface-based morphometry, subcortical volumes using FIRST, DT MRI metrics using region of interest and tractography approaches, and RS fMRI using a model free approach...
March 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28265120/a-genome-wide-gene-by-trauma-interaction-study-of-alcohol-misuse-in-two-independent-cohorts-identifies-prkg1-as-a-risk-locus
#14
R Polimanti, J Kaufman, H Zhao, H R Kranzler, R J Ursano, R C Kessler, J Gelernter, M B Stein
Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (STARRS, N=16 361) and the Yale-Penn (N=8084) cohorts. Because the two cohorts were assessed using different instruments, we derived separate dimensional alcohol misuse scales and applied a proxy-phenotype study design...
March 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28265119/evidence-for-neuroplastic-compensation-in-the-cerebral-cortex-of-persons-with-depressive-illness
#15
R Bansal, D J Hellerstein, B S Peterson
We yoked anatomical brain magnetic resonance imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week's duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and end point in 41 patients and once in 39 healthy controls...
March 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28265118/risk-alleles-of-genes-with-monoallelic-expression-are-enriched-in-gain-of-function-variants-and-depleted-in-loss-of-function-variants-for-neurodevelopmental-disorders
#16
V Savova, S Vinogradova, D Pruss, A A Gimelbrant, L A Weiss
Over 3000 human genes can be expressed from a single allele in one cell, and from the other allele-or both-in neighboring cells. Little is known about the consequences of this epigenetic phenomenon, monoallelic expression (MAE). We hypothesized that MAE increases expression variability, with a potential impact on human disease. Here, we use a chromatin signature to infer MAE for genes in lymphoblastoid cell lines and human fetal brain tissue. We confirm that across clones MAE status correlates with expression level, and that in human tissue data sets, MAE genes show increased expression variability...
March 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28259859/-molecular-psychiatry-research-in-hungary-editorial
#17
Janos M Rethelyi
No abstract text is available yet for this article.
December 2016: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28242873/reduction-of-smoking-urges-with-intranasal-insulin-a-randomized-crossover-placebo-controlled-clinical-trial
#18
A Hamidovic, M Khafaja, V Brandon, J Anderson, G Ray, A M Allan, M R Burge
Many cigarette smokers express a desire to quit smoking, but ~85% of cessation attempts fail. In our attempt to delineate genetic modulators of smoking persistence, we have earlier shown that a locus within an ~250 kb haplotype block spanning the 5' untranslated region region of insulin-degrading enzyme is associated with serum cotinine levels; the study's measure of smoking quantity. Based on our findings, and coupled with recent preclinical studies showing the importance of multiple neuropeptides in reinstatement of drug use, we formulated intranasal insulin to evaluate its efficacy during acute abstinence from smoking...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28242872/the-familial-co-aggregation-of-asd-and-adhd-a-register-based-cohort-study
#19
L Ghirardi, I Brikell, R Kuja-Halkola, C M Freitag, B Franke, P Asherson, P Lichtenstein, H Larsson
Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28242871/attenuation-of-ketamine-induced-impairment-in-verbal-learning-and-memory-in-healthy-volunteers-by-the-ampa-receptor-potentiator-pf-04958242
#20
M Ranganathan, N DeMartinis, B Huguenel, F Gaudreault, M M Bednar, C L Shaffer, S Gupta, J Cahill, M A Sherif, J Mancuso, L Zumpano, D C D'Souza
There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine...
February 28, 2017: Molecular Psychiatry
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