Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA305296 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Anorexia nervosa (AN), bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN, and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. Additionally, few if any studies have interrogated postmortem brain tissue for evidence of eQTLs associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN, and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a non-psychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, e.g., eating disorders (ED; N=15), and obsessive-compulsive disorder/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and non-psychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared to controls and OCD cases compared to controls, respectively (FDR < 5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain datasets. Gene expression data from the dorsolateral prefrontal cortex (DLPFC) from postmortem tissue on 133 subjects - 15 eating disorder (ED) patients, 16 obessive compulsive disorder (OCD) patients, and 102 non-psychiatric controls - run on the Illumina HumanHT-12 v3 microarray
2014-08-08 | E-GEOD-60190 | biostudies-arrayexpress
Project description:Neurogenetics of Obsessive-Compulsive Disorder
| PRJNA588485 | ENA
Project description:Neurogenetics of Obsessive-Compulsive Disorder
| PRJNA588486 | ENA
Project description:Anorexia nervosa (AN), bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN, and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. Additionally, few if any studies have interrogated postmortem brain tissue for evidence of eQTLs associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN, and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a non-psychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, e.g., eating disorders (ED; N=15), and obsessive-compulsive disorder/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and non-psychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared to controls and OCD cases compared to controls, respectively (FDR < 5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain datasets.
2014-08-08 | GSE60190 | GEO
Project description:<p>Excoriation disorder (ED), also known as neurotic excoriations, is a psychocutaneous disorder characterized by repetitive, compulsive picking of the skin leading to secondary tissue damage. ED carries an estimated prevalence of 1.4%, and is associated with significant social dysfunction, as patients often spend several hours each day performing compulsive behaviors leading to absence from work, school or other social events. Despite the significant impact on quality of life, there is still a lack of understanding of the factors involved in disease precipitation or progression, highlighting a need for identification of novel biomarkers of disease. The study of metabolic alterations, through plasma metabolomics, may lead to a greater understanding of disease pathogenesis, as metabolic alterations have been identified in related conditions such as obsessive-compulsive disorder (OCD) and in animal models of compulsive behavior. However, the metabolomic abnormalities present in ED have yet to be described. The purpose of this study is to perform an untargeted comparative plasma metabolomics analysis on ED patients and healthy controls to characterize the metabolic alterations in ED. Mass spectrometry quantified 76 total metabolites, 20 of which were identified as significantly different between ED and healthy controls, with four being increased and 16 being decreased in ED.</p><p><br></p>
2024-04-03 | MTBLS9118 | MetaboLights
Project description:Constitutive knockout of the obsessive-compulsive disorder-associated protein, SAPAP3, results in repetitive motor dysfunction, such as excessive grooming, caused by increased mGluR5 activity in striatal medium spiny neurons (MSNs). However, signaling mechanisms that mediate mGluR5-dependent grooming dysfunction are not fully understood. Here, we investigate the function of the striatal signaling hub protein, spinophilin, in regulating mGluR5 phosphorylation and protein interactions, which may predict spinophilin’s role in regulating mGluR5-dependent grooming dysfunction.
2022-12-14 | PXD034053 | Pride
Project description:Chronic stress is a major triggering factor for neuropsychiatric disorders including obsessive-compulsive disorder (OCD), a mental health condition characterized by motor stereotypies and striatal overactivation. However, the mechanisms at the cell- and microcircuit-level through which stress triggers motor symptoms is currently unknown. Here, we report that chronic stress (CS) in mice alters dorsomedial striatum (DMS) function, by affecting GABAergic interneuron populations and somatostatin-positive (SOM) interneurons in particular. Specifically, we show that CS impairs communication between SOM interneurons and medium spiny neurons, promoting striatal overactivation / disinhibition and increased motor output. Using probabilistic machine learning for analyzing animal behavior we further demonstrate that in vivo chemogenetic manipulation of SOM interneurons in DMS modulates motor phenotypes in stressed mice. Altogether, we propose a causal link between dysfunction of striatal SOM interneurons and motor symptoms in stress-related neuropsychiatric disorders.
2022-12-13 | PXD031193 | Pride
Project description:Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation
| PRJNA622825 | ENA
Project description:The aim of the study is to identify the global messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression profiling in peripheral blood from thirty patients with Obsessive Compulsive Disorders (OCD) and thirty paired normal controls.
2018-08-30 | GSE78104 | GEO
Project description:Obsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1-3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier. We use genome wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin (CDH2), catenin alpha2 (CTNNA2), ataxin-1 (ATXN1), and plasma glutamate carboxypeptidase (PGCP). Two different case-only variants targeted the same approximately 500-bp highly conserved regulatory element between the cadherin genes CDH2 and DSC3. We functionally test these variants in a human neuroblastoma cell line and show that they cause significant changes in gene expression, likely due to disrupted transcription factor binding. This work demonstrates how we can use the unique genetics of dog breeds, and mechanistic similarities between human and dog diseases, to find genes and regulatory pathways underlying complex psychiatric disorders. Affymetrix SNP arrays were performed according to the manufacturer's directions. Genome wide association analysis was performed for 87 doberman pinshcers OCD cases and 63 breed-matched controls.
2013-12-20 | E-GEOD-53488 | biostudies-arrayexpress