ORBITOFRONTAL THICKNESS AS A MEASURE FOR TREATMENT RESPONSE PREDICTION IN OBSESSIVE-COMPULSIVE DISORDER.

BACKGROUND: Early prediction of treatment response could reduce exposure to ineffective treatments and optimize the use of medical resources. Neuroimaging techniques have been used to identify biomarkers that are predictive of outcomes. The aims of this study were to investigate orbitofrontal cortex (OFC) thickness as a potential morphometric biomarker to discriminate outcomes in obsessive-compulsive disorder (OCD) and then to reexamine this biomarker in an independent cohort METHODS: Using a logistic regression model based on the mean baseline thickness of subregions of the OFC, we estimated the probability of treatment response in 29 treatment-naïve OCD patients who participated in a clinical trial. That algorithm was then tested in an independent cohort of 12 patients with a confirmed diagnosis of refractory OCD RESULTS: Among the treatment-naïve OCD patients, measures of OFC thickness statistically significantly differentiated responders (n = 13) and nonresponders (n = 16), with an overall classification accuracy of ≈80%, a sensitivity of 77% (10/13), and a specificity of 81% (13/16). Of the refractory OCD patients in the second independent cohort, 67% were correctly classified as nonresponders. The most discriminative measures in the initial cohort of treatment-naïve patients were the thicknesses of the left and right medial OFC (P = .009 and P = .028, respectively) CONCLUSIONS: We found OFC thickness to be a strong predictor of treatment response in treatment-naïve OCD patients. Although there are not yet any brain imaging biomarkers with clinical utility, our results highlight the potential of these measures as tools for predicting treatment outcomes in OCD.

Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder.

Nearly one-third of patients with obsessive-compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.

Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naïve patients.

BACKGROUND: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. METHOD: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naïve OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). RESULTS: Scores on the "aggression" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the "sexual/religious" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the "hoarding" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the "contamination" or "symmetry" dimensions were found. CONCLUSIONS: Building upon preexisting findings, our data with treatment-naïve OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions.