Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) [2005/55628-8]

FAPESP [06/61459-7, 06/50273-0, 2008/10257-0, 06/58286-3, 2005/04206-6]

FAPESP

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education)

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) [4375/08-4]

Medtronic

Medtronic

Eli Lilly

Eli Lilly

McNeil

McNeil

Cyberonics

Cyberonics

NIMH

NIMH

NARSAD

NARSAD

TSA

TSA

OCF

OCF

Tufts University

Tufts University

MGH Psychiatry Academy

MGH Psychiatry Academy

BrainCells

BrainCells

Systems Research and Applications Corporation

Systems Research and Applications Corporation

Boston University

Boston University

Catalan Agency for Health Technology Assessment and Research

Catalan Agency for Health Technology Assessment and Research

National Association of Social Workers Massachusetts

National Association of Social Workers Massachusetts

Massachusetts Medical Society

Massachusetts Medical Society

NIDA

NIDA

German Research Foundation/Federal Ministry for Education and Research

German Research Foundation/Federal Ministry for Education and Research

Oxford University Press

Oxford University Press

NIH

NIH

NIA

NIA

AHRQ

AHRQ

Janssen Pharmaceuticals

Janssen Pharmaceuticals

Forest Research Institute

Forest Research Institute

Shire Development

Shire Development

Northstar

Northstar

Janssen

Janssen

AstraZeneca

AstraZeneca

Lundbeck

Lundbeck

Solvay

Solvay