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Genetic psychiatry

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https://www.readbyqxmd.com/read/28222122/poor-replication-validity-of-biomedical-association-studies-reported-by-newspapers
#1
Estelle Dumas-Mallet, Andy Smith, Thomas Boraud, François Gonon
OBJECTIVE: To investigate the replication validity of biomedical association studies covered by newspapers. METHODS: We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study...
2017: PloS One
https://www.readbyqxmd.com/read/28194008/genetic-otx2-mis-localization-delays-critical-period-plasticity-across-brain-regions
#2
H H C Lee, C Bernard, Z Ye, D Acampora, A Simeone, A Prochiantz, A A Di Nardo, T K Hensch
Accumulation of non-cell autonomous Otx2 homeoprotein in postnatal mouse visual cortex (V1) has been implicated in both the onset and closure of critical period (CP) plasticity. Here, we show that a genetic point mutation in the glycosaminoglycan recognition motif of Otx2 broadly delays the maturation of pivotal parvalbumin-positive (PV+) interneurons not only in V1 but also in the primary auditory (A1) and medial prefrontal cortex (mPFC). Consequently, not only visual, but also auditory plasticity is delayed, including the experience-dependent expansion of tonotopic maps in A1 and the acquisition of acoustic preferences in mPFC, which mitigates anxious behavior...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194005/genetic-inhibition-of-neurotransmission-reveals-role-of-glutamatergic-input-to-dopamine-neurons-in-high-effort-behavior
#3
M A Hutchison, X Gu, M F Adrover, M R Lee, T S Hnasko, V A Alvarez, W Lu
Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194004/genetic-contributions-to-self-reported-tiredness
#4
V Deary, S P Hagenaars, S E Harris, W D Hill, G Davies, D C M Liewald, A M McIntosh, C R Gale, I J Deary
Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194001/enhancing-vta-cav1-3-l-type-ca-2-channel-activity-promotes-cocaine-and-mood-related-behaviors-via-overlapping-ampa-receptor-mechanisms-in-the-nucleus-accumbens
#5
A Martínez-Rivera, J Hao, T F Tropea, T P Giordano, M Kosovsky, R C Rice, A Lee, R L Huganir, J Striessnig, N A Addy, S Han, A M Rajadhyaksha
Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca(2+) channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28193370/-characterisation-of-three-polymorphisms-of-the-tryptophan-hydroxylase-2-gene-in-a-sample-of-colombian-population-with-major-depressive-disorder
#6
Adriana Martínez-Idárraga, Irene Riveros-Barrera, Ricardo Sánchez, Luis Eduardo Jaramillo, José Manuel Calvo-Gómez, Juan José Yunis-Londoño
OBJECTIVE: Identify whether rs11179000, rs136494 and rs4570625 polymorphisms of the tryptophan hydroxylase 2 gene, are associated with a major depressive disorder in a sample of the Colombian population. METHODS: Case-control study was conducted in which a comparison was made between subjects diagnosed with major depressive disorder at some point in adulthood or active symptoms at the time of evaluation, and subjects with no psychiatric disease. Subjects were studied in the Department of Psychiatry, Faculty of Medicine and the Institute of Genetics at the National University of Colombia...
January 2017: Revista Colombiana de Psiquiatría
https://www.readbyqxmd.com/read/28174595/hla-drb1-03-as-a-possible-common-etiology-of-schizophrenia-graves-disease-and-type-2-diabetes
#7
Aicha Sayeh, Cheker Ben Cheikh, Ali Mardessi, Meriem Mrad, Brahim Nsiri, Abdelaziz Oumaya, Najiba Fekih-Mrissa
BACKGROUND: Autoimmune diseases and schizophrenia share many common features. Association studies confirm a shared genetic association in the human leukocyte antigen (HLA) region between schizophrenia and most autoimmune diseases. To our knowledge, the simultaneous syndromes of Graves' disease (GD) and type 2 diabetes (T2D) in schizophrenia are rare in Tunisia. CASE PRESENTATION: We report a case of a 42-year-old woman admitted to the department of psychiatry for an acute relapse of chronic schizophrenia...
2017: Annals of General Psychiatry
https://www.readbyqxmd.com/read/28167838/glrb-allelic-variation-associated-with-agoraphobic-cognitions-increased-startle-response-and-fear-network-activation-a-potential-neurogenetic-pathway-to-panic-disorder
#8
J Deckert, H Weber, C Villmann, T B Lonsdorf, J Richter, M Andreatta, A Arias-Vasquez, L Hommers, L Kent, C Schartner, S Cichon, C Wolf, N Schaefer, C R von Collenberg, B Wachter, R Blum, D Schümann, R Scharfenort, J Schumacher, A J Forstner, C Baumann, M A Schiele, S Notzon, P Zwanzger, J G E Janzing, T Galesloot, L A Kiemeney, A Gajewska, E Glotzbach-Schoon, A Mühlberger, G Alpers, T Fydrich, L Fehm, A L Gerlach, T Kircher, T Lang, A Ströhle, V Arolt, H-U Wittchen, R Kalisch, C Büchel, A Hamm, M M Nöthen, M Romanos, K Domschke, P Pauli, A Reif
The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3...
February 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28167836/autism-associated-dyrk1a-truncation-mutants-impair-neuronal-dendritic-and-spine-growth-and-interfere-with-postnatal-cortical-development
#9
T Dang, W Y Duan, B Yu, D L Tong, C Cheng, Y F Zhang, W Wu, K Ye, W X Zhang, M Wu, B B Wu, Y An, Z L Qiu, B L Wu
Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development...
February 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28167616/towards-trans-diagnostic-mechanisms-in-psychiatry-neurobehavioral-profile-of-rats-with-a-loss-of-function-point-mutation-in-the-dopamine-transporter-gene
#10
Valentina Vengeliene, Anton Bespalov, Martin Roßmanith, Sandra Horschitz, Stefan Berger, Ana L Relo, Hamid R Noori, Peggy Schneider, Thomas Enkel, Dusan Bartsch, Miriam Schneider, Berthold Behl, Anita C Hansson, Patrick Schloss, Rainer Spanagel
The Research Domain Criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here we used a new genetic rat model with a loss of function point mutation in the dopamine transporter (DAT) gene (Slc6a3_N157K) to systematically study the RDoC matrix (www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml). First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains - negative and positive valence systems, cognitive, social, and in arousal/regulatory systems...
February 6, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28166481/the-benefits-risks-and-costs-of-privacy-patient-preferences-and-willingness-to-pay
#11
David E Trachtenbarg, Carl Asche, Shweta Ramsahai, Joy Duling, Jinma Ren
OBJECTIVE: Multiple surveys show patients want medical privacy, however, there are costs to maintain privacy. There are also risks if information is not shared. A review of previous surveys found most surveys asked questions about patient's privacy concerns and willingness to share their medical information. We found only one study that asked about sharing medical information for better care and no survey that asked patients about the risk, cost or comparison between medical privacy and privacy in other areas...
February 6, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28138115/mania-in-wolfram-s-disease-from-bedside-to-bench
#12
Seshadri Sekhar Chatterjee, Sayantanava Mitra, Salil Kumar Pal
Wolfram syndrome is a relatively unexplored entity in clinical psychiatry. Historically, the discovery of a specific WFS1 gene had generated huge fanfare regarding specific genetic causations of psychiatric disorders. While the initial enthusiasm has faded now, association of Wolfram syndrome with psychiatric illnesses like schizophrenia, psychosis and suicidal behavior still remain important for understanding biological underpinnings of such disorders. We report a case of Wolfram syndrome presenting with multiple manic episodes, discuss possible genetic underpinnings for the affective symptoms and then discuss certain issues regarding management...
February 28, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28121394/symptoms-of-major-depression-their-stability-familiality-and-prediction-by-genetic-temperamental-and-childhood-environmental-risk-factors
#13
Kenneth S Kendler, Steven H Aggen
BACKGROUND: Psychiatry has long sought to develop biological diagnostic subtypes based on symptomatic differences. This effort assumes that symptoms reflect, with good fidelity, underlying etiological processes. We address this question for major depression (MD). METHODS: We examine, in twins from a population-based registry, similarity in symptom endorsement in individuals meeting criteria for last-year MD at separate interview waves and in concordant twin pairs...
January 25, 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/28116236/the-neural-correlates-and-clinical-characteristics-of-psychosis-in-the-frontotemporal-dementia-continuum-and-the-c9orf72-expansion
#14
Emma M Devenney, Ramon Landin-Romero, Muireann Irish, Michael Hornberger, Eneida Mioshi, Glenda M Halliday, Matthew C Kiernan, John R Hodges
OBJECTIVE: This present study aims to address the gap in the literature regarding the severity and underlying neural correlates of psychotic symptoms in frontotemporal dementia with and without the C9orf72 gene expansion. METHODS: Fifty-six patients with behavioural variant frontotemporal dementia (20 with concomitant amyotrophic lateral sclerosis) and 23 healthy controls underwent neuropsychological assessments, detailed clinical interview for assessment of psychosis symptoms, brain MRI and genetic testing...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28115744/a-genome-wide-association-study-identifies-two-novel-susceptibility-loci-and-trans-population-polygenicity-associated-with-bipolar-disorder
#15
M Ikeda, A Takahashi, Y Kamatani, Y Okahisa, H Kunugi, N Mori, T Sasaki, T Ohmori, Y Okamoto, H Kawasaki, S Shimodera, T Kato, H Yoneda, R Yoshimura, M Iyo, K Matsuda, M Akiyama, K Ashikawa, K Kashiwase, K Tokunaga, K Kondo, T Saito, A Shimasaki, K Kawase, T Kitajima, K Matsuo, M Itokawa, T Someya, T Inada, R Hashimoto, T Inoue, K Akiyama, H Tanii, H Arai, S Kanba, N Ozaki, I Kusumi, T Yoshikawa, M Kubo, N Iwata
Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10(-9)), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115742/mef2c-transcription-factor-is-associated-with-the-genetic-and-epigenetic-risk-architecture-of-schizophrenia-and-improves-cognition-in-mice
#16
A C Mitchell, B Javidfar, V Pothula, D Ibi, E Y Shen, C J Peter, L K Bicks, T Fehr, Y Jiang, K J Brennand, R L Neve, J Gonzalez-Maeso, S Akbarian
Large-scale consortia mapping the genomic risk architectures of schizophrenia provide vast amounts of molecular information, with largely unexplored therapeutic potential. We harnessed publically available information from the Psychiatric Genomics Consortium, and report myocyte enhancer factor 2C (MEF2C) motif enrichment in sequences surrounding the top scoring single-nucleotide polymorphisms within risk loci contributing by individual small effect to disease heritability. Chromatin profiling at base-pair resolution in neuronal nucleosomes extracted from prefrontal cortex of 34 subjects, including 17 cases diagnosed with schizophrenia, revealed MEF2C motif enrichment within cis-regulatory sequences, including neuron-specific promoters and superenhancers, affected by histone H3K4 hypermethylation in disease cases...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115739/genome-wide-association-study-of-therapeutic-opioid-dosing-identifies-a-novel-locus-upstream-of-oprm1
#17
A H Smith, K P Jensen, J Li, Y Nunez, L A Farrer, H Hakonarson, S D Cook-Sather, H R Kranzler, J Gelernter
Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose. In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115737/cannabis-use-and-risk-of-schizophrenia-a-mendelian-randomization-study
#18
J Vaucher, B J Keating, A M Lasserre, W Gan, D M Lyall, J Ward, D J Smith, J P Pell, N Sattar, G Paré, M V Holmes
Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093568/gwas-meta-analysis-reveals-novel-loci-and-genetic-correlates-for-general-cognitive-function-a-report-from-the-cogent-consortium
#19
J W Trampush, M L Z Yang, J Yu, E Knowles, G Davies, D C Liewald, J M Starr, S Djurovic, I Melle, K Sundet, A Christoforou, I Reinvang, P DeRosse, A J Lundervold, V M Steen, T Espeseth, K Räikkönen, E Widen, A Palotie, J G Eriksson, I Giegling, B Konte, P Roussos, S Giakoumaki, K E Burdick, A Payton, W Ollier, M Horan, O Chiba-Falek, D K Attix, A C Need, E T Cirulli, A N Voineskos, N C Stefanis, D Avramopoulos, A Hatzimanolis, D E Arking, N Smyrnis, R M Bilder, N A Freimer, T D Cannon, E London, R A Poldrack, F W Sabb, E Congdon, E D Conley, M A Scult, D Dickinson, R E Straub, G Donohoe, D Morris, A Corvin, M Gill, A R Hariri, D R Weinberger, N Pendleton, P Bitsios, D Rujescu, J Lahti, S Le Hellard, M C Keller, O A Andreassen, I J Deary, D C Glahn, A K Malhotra, T Lencz
The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT)...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28089652/hippocampal-prefrontal-connectivity-as-a-translational-phenotype-for-schizophrenia
#20
REVIEW
Florian Bähner, Andreas Meyer-Lindenberg
Finding novel biological targets in psychiatry has been difficult, partly because current diagnostic categories are not defined by pathophysiology and difficult to model in animals. The study of species-conserved systems-level mechanisms implicated in psychiatric disease could be a promising strategy to address some of these difficulties. Altered hippocampal-prefrontal (HC-PFC) connectivity during working memory (WM) processing is a candidate for such a translational phenotype as it has been repeatedly associated with impaired cognition in schizophrenia patients and animal models for psychiatric risk factors...
February 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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