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Obsessive-Compulsive Disorders Research

Obsessions and Compulsions During Pregnancy and Postpartum

Principal Investigator: Gerald Nestadt, M.D., M.P.H.

The goal of this research is to better understand the factors associated with obsessions, compulsions, and depression during pregnancy and the postpartum. Women will be followed from about midway through their pregnancies until about 6-months postpartum with online questionnaires and interviews, and biological specimens will be analyzed for cytokines, hormones, and immune cell types. Recruitment of study participants will begin in September/October 2020. The study is funded by the National Institute of Mental Health (NIMH). For more information, please contact Janice Krasnow, Ph.D. at (443) 223-8151 or JHMI IRB #212313

Family and Genetic Studies of OCD

Principal Investigator: Gerald Nestadt, M.D., M.P.H.

The goal of this research program is to elucidate the causes and pathophysiology of obsessive-compulsive disorder (OCD).  The program was initiated in the 1990’s to investigate the genetic etiology of OCD. 

In the OCD Family Study (1996-2001), we evaluated over 800 individuals in 153 families. We found the occurrence of OCD to be six times greater in relatives of OCD cases than in relatives of the control group. Other anxiety disorders, especially agoraphobia and generalized anxiety disorder, also were more prevalent in case families. Segregation analysis provided evidence that genes of major effect are involved in OCD. 

In the OCD Collaborative Genetics Study (2001-2007), we directed a genetics study of OCD in collaboration with five other academic centers in the United States. The collaboration diagnostically evaluated and collected DNA samples from over 200 affected sibling pairs, and completed the first large genome-wide genetic linkage scan of OCD. We found evidence of genetic linkage of OCD to regions on chromosomes 1, 3, 6, 7, and 15. We also found intrafamilial correlation of factor dimensions, especially hoarding behavior, in OCD families.  In addition, we found significant linkage of compulsive hoarding behavior to a region on chromosome 14. We have been following up these findings with fine mapping of these regions and family-based association studies of functional candidate genes.  This research has been funded by grants from the National Institutes of Health, the OCD Foundation, and the James E. Marshall OCD Foundation.

In the OCD Collaborative Genetics Association Study (2007-2012), we and our collaborators at five other academic centers interviewed, and collected DNA samples from, 2000 individuals with OCD and their parents.  We conducted a genome-wide association study to identify even smaller chromosomal regions associated with OCD.  Our most significant finding was for a genetic marker on chromosome 9, near the protein tyrosine phosphatase receptor type D gene (PTPRD). This gene is involved in the differentiation of glutamatergic synapses (Molecular Psychiatry, 2015).

Currently, in collaboration with Dr. David Goldstein’s laboratory at Columbia University, we are conducting exome sequencing on OCD-affected individuals and their unaffected parents, in order to identify rare (de novo) genetic variants associated with OCD.  Our groups also are conducting whole genome sequencing of families with multiple-affected relatives, in order to identify rare genetic variants strongly predisposing to some types of OCD.

In addition, we are using questionnaires and a computer-based task to explore uncertainty and decision-making in OCD and other disorders.

Our research continues to be funded by the National Institute of Mental Health (NIMH), and the James E. Marshall OCD Foundation.

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