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

Abstract

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.

Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder

“…Evidence from electrophysiology and neuroimaging (1) studies has long indicated the involvement of the basal ganglia in OCD. Greater putamen and caudate volume is often (2-5) but not consistently found, and findings may be dependent on the age of the recruited samples, treatment history, or treatment status (12). We did not find striatal volume alterations in the overall OCD patient group, but in line with a previous report (8), we observed a relatively preserved volume of the putamen and nucleus accumbens during aging in patients.…”

“…Moreover, only the middle frontal gray matter finding (a region not overlapping with the main group effects) remained significant after we controlled for the differing sample characteristics of the medicated versus unmedicated patients in a multiple regression analysis. Therefore, it is possible that gray matter alterations in the middle frontal cortex may be partially attributable to current medication use, a finding that deserves further investigation, ideally using longitudinal designs (12).…”

Structural alterations in patients with obsessive–compulsive disorder: a surface-based analysis of cortical volume, surface area and thickness

“…7,56,57 However, although our sample was partly medicated and not comorbidity-free, these factors did not show any significant effect on the present results after correcting for multiple comparisons. Considering that on an uncorrected threshold an effect was found in certain clusters, it cannot be excluded that comorbidity or medical treatment had a certain influence on grey matter structure.…”

Evidências de alterações neurais na Terapia Cognitivo-Comportamental: uma revisão da literatura

“…Antes do tratamento, os pacientes com TOC apresentavam menor substância cinzenta no putâmen esquerdo, no cór-tex orbitofrontal medial bilateral e no córtex cingulado anterior esquerdo em comparação com os controles. Após o tratamento, tanto pacientes tratados com fluoxetina quanto TCC não apresentavam diferença em relação aos controles na quantidade de substância cinzenta no putâmen esquerdo (Hoexter et al, 2012).…”