Divergent Structural Responses to Pharmacological Interventions in Orbitofronto-Striato-Thalamic and Premotor Circuits in Obsessive-Compulsive Disorder

Prior efforts to dissect etiological and pharmacological modulations in brain morphology in obsessive-compulsive disorder (OCD) are often undermined bymethodological and sampling constraints, yielding conflicting conclusions and no reliable neuromarkers. Here we evaluated alteration of regional gray matter volume including effect size (Cohen's d value) in 95 drug-naive patients (age range: 18-55) compared to 95 healthy subjects (age: 18-63), then examined pharmacological effects in 65 medicated (age: 18-57) and 73 medication-free patients (age: 18-61). Robustness of statistical outcomes and effect sizes was rigorously tested with Monte Carlo cross-validation. Relative to controls, both drug-naive and medication-free patients exhibited comparable volumetric increasesmainly in the left thalamus (d=0.90, 0.82, respectively), left ventral striatum (d=0.88, 0.67), bilateralmedial orbitofrontal cortex (d=0.86, 0.71; 0.90, 0.73), and left inferior temporal gyrus (d=0.83, 0.66), and decreased volumes in left premotor/presupplementary motor areas (d=-0.83, -0.71). Interestingly, abnormalities in the thalamus and medial orbitofrontal cortex were present in medicated patients whereas entirely absent in premotor and ventral striatum. It suggests that pharmacotherapy elicited divergent responses in orbitofronto-striato-thalamic and premotor circuits, which warrants the design of longitudinal studies investigating the potential of these neuromarkers in stratified treatments of OCD. (C) 2017 The Authors. Published by Elsevier B.V.