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Caudate Gray Matter Volume in Obsessive-Compulsive Disorder Is Influenced by Adverse Childhood Experiences and Ongoing Drug Treatment

Benedetti, Francesco MD*†; Poletti, Sara PhD*†; Radaelli, Daniele PhD*†; Pozzi, Elena PhD*†; Giacosa, Chiara PhD*†; Ruffini, Chiara MD*; Falini, Andrea MD†‡; Smeraldi, Enrico MD*†

Journal of Clinical Psychopharmacology: August 2012 - Volume 32 - Issue 4 - p 544–547
doi: 10.1097/JCP.0b013e31825cce05
Brief Reports

Background Exposure to adverse childhood experiences (ACE) increases the risk of adult physical and mental health disorders, including obsessive-compulsive disorder (OCD), and influences adult cortical neural responses and gray matter (GM) volumes. Robust neuroimaging findings associated OCD with corticostriatal dysfunction and with abnormal morphology and metabolism of cortical areas and basal ganglia.

Methods We explored the GM correlates of ACE in 40 patients with OCD (15 drug-naive and 25 drug-treated patients) with magnetic resonance imaging voxel-based morphometry at 3.0 T. Regional GM volumes were the dependent variable, and drug treatment (naive vs treated) and breadth of exposure to ACE (high vs low) were the factors of interest. Sex, duration of illness, and handedness were considered as nuisance covariates. Whole brain statistical threshold was P < 0.05 familywise error corrected for multiple comparisons.

Results Patients with higher levels of exposure to ACE showed increased GM volume in the head of the left caudate nucleus. Ongoing drug treatment was associated with reduced GM volume in the same area. Earlier age at onset of OCD, need for medication treatment, and mixed handedness were correlated with higher levels of ACE.

Conclusions Exposure to ACE increased, and ongoing drug treatment decreased, caudate GM in OCD. Increased volume and metabolism of the caudate nucleus have been consistently associated with OCD. Our findings suggest a detrimental effect of ACE on the brain underpinnings of OCD, with an opposite effect of medications.

From the *Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele; †CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele; and ‡Department of Neuroradiology, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.

Received April 18, 2011; accepted after revision January 17, 2012.

Reprints: Francesco Benedetti, MD, Istituto Scientifico Ospedale San Raffaele, Department of Clinical Neurosciences, San Raffaele Turro, Via Stamira d’Ancona 20, Milano, Italy (e-mail

The CERMAC received research grants from the following: Italian Ministry of University and Scientific Research, Italian Ministry of Health, European Union (FP7 grant 222963), Trenta ore per la Vita Association, and Janssen-Cilag.

© 2012 Lippincott Williams & Wilkins, Inc.