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      The relationship between obsessive-compulsive symptoms andPARKINgenotype: The CORE-PD study : OC Symptoms andPARKINGenotype

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          Most cited references 29

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          Toward a neurobiology of obsessive-compulsive disorder.

           A Graybiel,  S. Rauch (2000)
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            Repeated cortico-striatal stimulation generates persistent OCD-like behavior.

            Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.
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              Genome-wide association study of obsessive-compulsive disorder.

              Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

                Author and article information

                [1 ]Department of Neurology; College of Physicians and Surgeons, Columbia University; New York NY USA
                [2 ]Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University; New York NY USA
                [3 ]Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University; New York NY USA
                [4 ]Department of Epidemiology; Mailman School of Public Health, Columbia University; New York NY USA
                [5 ]Department of Neurological Sciences; Rush University Medical Center; Chicago IL USA
                [6 ]Struthers Parkinson's Center, Park Nicollet Clinic; Golden Valley MN USA
                [7 ]The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center; New York NY USA
                [8 ]Department of Neurology; Albert Einstein College of Medicine; Bronx New York USA
                [9 ]Dr. John T Macdonald Foundation; Department of Human Genetics; Miami Institute for Human Genomics, Miller School of Medicine, University of Miami; Miami FL USA
                [10 ]Parkinson's Institute; Sunnyvale CA USA
                [11 ]San Francisco Veterans Affairs Medical Center and University of California-San Francisco; San Francisco CA USA
                [12 ]Central DuPage Hospital, Neurosciences Institute, Movement Disorders Center; Winfield IL USA
                [13 ]Department of Neurology; at NorthShore University Health System; Evanston IL USA
                [14 ]Department of Neurology; University of Chicago, Pritzker School of Medicine; Chicago IL USA
                [15 ]Butler Hospital; Providence RI USA
                [16 ]Department of Neurology; Alpert Medical School of Brown University; Providence RI USA
                [17 ]Department of Neurology; College of Medicine, University of Tennessee Health Science Center; Memphis TN USA
                [18 ]New York State Department of Health Wadsworth Center; Albany NY USA
                [19 ]Parkinson's Disease and Movement Disorders Center of Albany Medical Center; Albany NY USA
                [20 ]Department of Neurology; Emory University; Atlanta GA USA
                [21 ]Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center, Portland, OR, USA, and Oregon Health & Science University; Portland OR USA
                [22 ]University of Puerto Rico; San Juan Puerto Rico
                [23 ]Division of Human Genetics; Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine; OH USA
                [24 ]Department of Pathology and Cell Biology; College of Physicians and Surgeons, Columbia University; New York NY USA
                [25 ]Center for Human Genetics; College of Physicians and Surgeons, Columbia University; New York NY USA
                [26 ]Department of Psychiatry; Columbia University Medical Center; New York NY USA
                Movement Disorders
                Mov Disord.
                February 2015
                February 2015
                November 12 2014
                : 30
                : 2
                : 278-283
                © 2014


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