title: Subcortical and cortical morphological anomalies as an endophenotype in obsessive-compulsive disorder.
abstract: Endophentoypes, quantifiable traits lying on the causal chain between a clinical phenotype and etiology, can be used to accelerate genomic discovery in obsessive-compulsive disorder (OCD). Here we identify the neuroanatomic changes that are shared by 22 OCD adult and adolescent patients and 25 of their unaffected siblings who are at genetic risk for the disorder. Comparisons were made against 47 age and sex matched healthy controls. We defined the surface morphology of the striatum, globus pallidus and thalamus, and thickness of the cerebral cortex. Patients with OCD show significant surface expansion compared with healthy controls, following adjustment for multiple comparisons, in interconnected regions of the caudate, thalamus and right orbitofrontal cortex. Their unaffected siblings show similar, significant expansion, most marked in the ventromedial caudate bilaterally, the right pulvinar thalamic nucleus and the right orbitofrontal cortex. These regions define a network that has been consistently implicated in OCD. In addition, both patients with OCD and unaffected siblings showed similar increased thickness of the right precuneus, which receives rich input from the thalamic pulvinar nuclei and the left medial temporal cortex. Anatomic change within the orbitofrontostriatal and posterior brain circuitry thus emerges as a promising endophenotype for OCD.
authors: 1] Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute,Bethesda, MD, USA [2] Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors: P
authors: P
authors: Shaw
authors: Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors: W
authors: W
authors: Sharp
authors: Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute,Bethesda, MD, USA.
authors: G
authors: G
authors: Sudre
authors: Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute,Bethesda, MD, USA.
authors: A
authors: A
authors: Wharton
authors: Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors: D
authors: D
authors: Greenstein
authors: Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors: A
authors: A
authors: Raznahan
authors: Brain Imaging Centre, Montreal Neuroimaging Institute and Hospital, McGill University, Montreal, QC, Canada.
authors: A
authors: A
authors: Evans
authors: 1] Kimel Family Imaging-Genetics Research Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Department of Psychiatry and Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
authors: M M
authors: MM
authors: Chakravarty
authors: 1] Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors: J P
authors: JP
authors: Lerch
authors: Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors: J
authors: J
authors: Rapoport
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D058068:Endophenotypes; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D059906:Neuroimaging; D009771:Obsessive-Compulsive Disorder / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D055815:Young Adult