Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group
Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.
T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.
In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen’s d effect sizes varied from ?0.10 to ?0.33.
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.
Error Processing and Inhibitory Control in Obsessive-Compulsive Disorder: A Meta-analysis Using Statistical Parametric Maps
Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies.
A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male).
Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001).
A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.
The identification of OCD-related subgroups based on comorbidity
Individuals with obsessive–compulsive disorder (OCD) frequently have other psychiatric disorders. This study employed latent class analysis (LCA) to explore whether there are underlying clinical constructs that distinguish “OCD-related” subgroups.
The study included 450 subjects, case and control probands and their first-degree relatives, and LCA was used to derive empirically based subgroups of 10 disorders: OCD, obsessive–compulsive personality disorder (OCPD), recurrent major depressive disorder (RMDD), separation anxiety disorder, panic disorder or agoraphobia (PD/AG), tic disorders (TD), generalized anxiety disorder (GAD), somatoform disorders (hypochondriasis or body dysmorphic disorder), pathologic skin picking or nail biting (PSP/NB), and eating disorders (EDs). The derived classes were compared on several clinical variables.
The best fitting model is a four-class structure: minimal disorder, predominant RMDD and GAD, “highly comorbid,” and PD/AG and TD. The nature and number of disorders represented suggests that the first classes are distributed ordinally on a dimension of severity, and the fourth class is qualitatively distinct. Support for this structure is based on the number of disorders, age at onset of OCD, neuroticism, and extraversion.
In this OCD enriched sample, LCA identified four classes of disorder. These classes appear to conform to two subgroups that may prove useful in investigating the etiology of OCD.
Familiality of Factor Analysis-Derived YBOCS Dimensions in OCD-Affected Sibling Pairs from the OCD Collaborative Genetics Study
Identification of familial, more homogenous characteristics of obsessive–compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions.
Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale–Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales.
After controlling for sex, age, and age of onset, robust sib–sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01).
Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.
Neural Responses to Facial Expressions of Disgust but not Fear are Modulated by Washing Symptoms in OCD
Washing symptoms in Obsessive-Compulsive Disorder (OCD) are associated with increased trait sensitivity to disgust. This study explored neural systems underlying sensitivity to symptom-unrelated disgust and fear in OCD using functional neuroimaging.
Seventeen OCD subjects and 19 controls viewed facial expressions of disgust and fear (versus neutral) presented just above the level of conscious awareness in a backward masking paradigm.
The OCD group showed greater activation than controls in the left ventrolateral prefrontal cortex, but reduced activation in the thalamus, to facial expressions of disgust. There were no between-group differences in response to fear. Further analysis using a median-split to divide OCD subjects into high and low washers suggested that the enhanced ventrolateral prefrontal cortex response was being driven by predominantly female OCD subjects with high washing symptoms. These subjects also reported higher levels of trait sensitivity to disgust.
These findings are consistent with previous reports of increased response to symptom-relevant and generally disgusting stimuli in neural regions associated with disgust and autonomic response processing in OCD patients with prominent washing symptoms. Together, these findings point to increased sensitivity to disgust stimuli as a component of the pathophysiology of the washing/contamination symptom dimension of OCD.