ABSTRACT
Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype.
ABSTRACT
CONTEXT: Cortical abnormalities have been noted in previous studies of major depressive disorder (MDD). OBJECTIVE: To hypothesize differences in regional cortical thickness among children with MDD, children with obsessive-compulsive disorder (OCD), and healthy controls. DESIGN: Cross-sectional study of groups. SETTING: Children's Hospital of Michigan in Detroit. PARTICIPANTS: A total of 24 psychotropic drug-naive pediatric patients with MDD (9 boys and 15 girls), 24 psychotropic drug-naive pediatric outpatients with OCD (8 boys and 16 girls), and 30 healthy controls (10 boys and 20 girls). INTERVENTION: Magnetic resonance imaging. MAIN OUTCOME MEASURE: Cortical thickness. RESULTS: In the right hemisphere of the brain, the pericalcarine gyrus was thinner in patients with MDD than in outpatients with OCD (P = .002) or healthy controls (P = .04), the postcentral gyrus was thinner in patients with MDD than in outpatients with OCD (P = .002) or healthy controls (P = .02), and the superior parietal gyrus was thinner in patients with MDD than in outpatients with OCD (P = .008) or healthy controls (P = .03). The outpatients with OCD and the healthy controls did not differ in these regions of the brain. The temporal pole was thicker in patients with MDD than in outpatients with OCD (P < .001) or healthy controls (P = .01), both of which groups did not differ in temporal pole thickness. The cuneus was thinner in patients with MDD than in outpatients with OCD (P = .008), but it did not differ from that in healthy controls. In the left hemisphere, the supramarginal gyrus was thinner in both patients with MDD (P = .04) and outpatients with OCD (P = .01) than in healthy controls, and the temporal pole was thicker in patients with MDD than in both healthy controls and outpatients with OCD (P < .001). CONCLUSIONS: To our knowledge, this is the first study to explore cortical thickness in pediatric patients with MDD. Although differences in some regions of the brain would be expected given neurobiological models of MDD, our study highlights some unexpected regions (ie, supramarginal and superior parietal gyri) that merit further investigation. These results underscore the need to expand exploration beyond the frontal-limbic circuit.
Subject(s)
Cerebral Cortex/pathology , Depressive Disorder, Major/diagnosis , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/diagnosis , Adolescent , Brain Mapping , Child , Comorbidity , Cross-Sectional Studies , Depressive Disorder, Major/genetics , Depressive Disorder, Major/pathology , Diagnosis, Differential , Dominance, Cerebral/genetics , Dominance, Cerebral/physiology , Female , Genetic Predisposition to Disease , Humans , Male , Obsessive-Compulsive Disorder/genetics , Obsessive-Compulsive Disorder/pathology , Organ Size/physiologyABSTRACT
The orbital frontal cortex (OFC) has been implicated in obsessive-compulsive disorder (OCD). Participants comprised 28 treatment-naïve pediatric OCD patients and 21 controls, who were examined using magnetic resonance imaging. OCD patients had larger right but not left OFC white matter volume than controls. This is fresh evidence implicating white matter in OCD.
