1/3 Brain Function and Genetics in Pediatric Obsessive-Compulsive Behaviors

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder that emerges during childhood or adolescence in as many as 80% of all case and is characterized by persistent, intrusive thoughts and urges (obsessions) and repetitive, intentional behaviors (compulsions). These compulsive behaviors are often, but not always, aimed at decreasing anxiety caused by obsessions. OCD represents the upper extreme of an underlying continuous trait distribution encompassing obsessive-compulsive behaviors common in the general population that are heritable and cross traditional diagnostic boundaries. Obsessive-compulsive behaviors (OCB) are common in children and adolescents. In addition to being the core features of OCD, they are often associated in youth with tic, grooming, generalized anxiety, and autism spectrum disorders. Structural and functional imaging studies have provided overwhelming evidence of the centrality of fronto-striatal-thalamic circuitry (FSTC) dysregulation in the pathogenesis of OCD and OCB. Within FSTC, the anterior cingulate cortex (ACC) has been one of the most consistently implicated regions in neurobiological models and in cognitive processes (e.g. cognitive control, error processing) associated with OCB. Both OCB and structural and functional abnormalities in FSTC have substantial heritability. However, little of the genetic variance in OCB has been explained and the neurobiological consequences of identified variants are poorly understood. The overall aim of this study is to determine the relationship between genetic variation, dysregulation of FSTC and OCB in youth, and to identify novel biological pathways relevant to the pathogenesis of OCB. These projects will provide a better understanding of the impact of genetic variants on FSTC dysregulation in the pathogenesis of OCD and OCB and lead to new diagnostic, therapeutic, and prevention strategies.

List of research focus titles: OCD, OCB, fMRI

  1. Morris, A., Ravishankar, M., Pivetta, L., Chowdury, A., Falco, D., Damoiseaux, J.S., Rosenberg, D.R.*, Bressler, S.L., Diwadkar, V.A*. Response hand and motor set differentially modulate the connectivity of brain pathways during simple uni-manual motor behavior. Brain Topography, 2018, 31(6), 985-1000. https://doi.org/10.1007/s10548-018-0664-5
  2. Friedman, A.L., Burgess, A., Ramaseshan, K., Easter, P., Khatib, D., Chowdury, A., Arnold, P.D., Hanna, G.L., Rosenberg, D.R.*, Diwadkar, V.A.* Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex. Psychiatry Research Neuroimaging, 2017, 260, 6-15. https://doi.org/10.1016/j.pscychresns.2016.12.005
  3. Diwadkar, V.A.*, Burgess, A., Hong, E., Rix, C., Arnold, P.D., Hanna, G.L., Rosenberg, D.R.* Dysfunctional activation and brain network profiles in youth with obsessive-compulsive disorder: A focus on the dorsal anterior cingulate during working memory. Frontiers in Human Neuroscience. 2015, 9, 149. https://doi.org/10.3389/fnhum.2015.00149