Objective-Structural brain imaging studies in Obsessive-Compulsive Disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in disease profile and developmental stage.Methods-To address these limitations, we conducted a meta-and mega-analysis of data from OCD sites worldwide. T 1 images from 1,830 OCD patients and 1,759 controls were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ in OCD patients and healthy controls. We additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients.Results-The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=−0.13; p=5.1x10 −3 , % difference −2.80) and larger pallidum volumes (d=0.16; p=1.6x10 −3 , % difference 3.16) compared to adult controls. Both effects were stronger in medicated patients compared to controls (d=−0.29; p=2.4x10 −5 , % difference −4.18 and d=0.29; p=1.2x10 −5 , % difference 4.38, respectively). Unmedicated pediatric patients had larger thalamic volumes (d=0.38, p=2.1x10 −3 ) compared to pediatric controls. None of these findings were mediated by sample characteristics such as mean age or field strength. Overall the mega-analysis yielded similar results. Conclusion-Our study indicates a different pattern of subcortical abnormalities in pediatric versus adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. This highlights the potential importance of neurodevelopmental alterations in OCD, and suggests that further research on neuroplasticity in OCD may be useful. IntroductionObsessive-compulsive disorder (OCD) is a neurodevelopmental disorder that affects 1-3% of the population (1; 2). In more than 50% of all OCD cases, symptoms emerge during Location of work and address for reprints: Premika S.W. Boedhoe, M.Sc.,

The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction.

IMPORTANCE Select cases of intractable obsessive-compulsive disorder (OCD) have undergone neurosurgical ablation for more than half a century. However, to our knowledge, there have been no randomized clinical trials of such procedures for the treatment of any psychiatric disorder.OBJECTIVE To determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD. DESIGN, SETTING, AND PARTICIPANTSIn a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC.INTERVENTIONS Patients randomized to active GVC had 2 distinct isocenters on each side irradiated at the ventral border of the anterior limb of the internal capsule. The patients randomized to sham GVC received simulated radiosurgery using the same equipment. MAIN OUTCOMES AND MEASURESScores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale at 1 year. Response was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or "much improved" CGI-I ratings.RESULTS Two of 8 patients randomized to active treatment responded at 12 months, and none of the 8 sham-GVC group patients responded (the absolute difference was not statistically significant: 0.25; 95% CI, Ϫ0.05 to 0.55; P = .11). At 12 months, median Y-BOCS scores were 23.5 in the active group vs 31 in the sham patients (P = .01). The median Y-BOCS scores decreased 28.6% in the active treatment group and 5.8% in the sham group (P = .04988). The median CGI-I scores were 3 and 4 in the active and sham treatment groups, respectively. At 54 months, 3 additional patients in the active group had become responders. Of the 4 sham-GVC patients who later received active GVC, 2 responded by post-GVC month 12. The most serious adverse event was an asymptomatic radiation-induced cyst in 1 patient. CONCLUSIONS AND RELEVANCEIn this preliminary trial, patients with intractable OCD who underwent GVC may have benefitted more than those who underwent sham surgery although the difference did not reach statistical significance. Additional research is necessary to determine if GVC is better than deep-brain stimulation.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01004302

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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.

BackgroundThere is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive–compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness.AimsTo investigate alterations in cortical thickness and subcortical volume in OCD.MethodIn total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken.ResultsSignificantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group x age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls.ConclusionsOur findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group x age interaction effects may be the result of altered neuroplasticity.