The Effects of Pharmacological Treatment on Functional Brain Connectome in Obsessive-Compulsive Disorder

Background: Previous neuroimaging studies of obsessive-compulsive disorder (OCD) have reported both baseline functional alterations and pharmacological changes in localized brain regions and connections; however, the effects of selective serotonin reuptake inhibitor (SSRI) treatment on the whole-brain functional network have not yet been elucidated. Methods: Twenty-five drug-free OCD patients underwent resting-state functional magnetic resonance imaging. After 16-weeks, seventeen patients who received SSRI treatment were rescanned. Twenty-three matched healthy control subjects were examined at baseline for comparison, and 21 of them were rescanned after 16 weeks. Topological properties of brain networks (including small-world, efficiency, modularity, and connectivity degree) were analyzed cross-sectionally and longitudinally with graph-theory approach. Results: At baseline, OCD patients relative to healthy control subjects showed decreased small-world efficiency (including local clustering coefficient, local efficiency, and small-worldness) and functional association between default-mode and frontoparietal modules as well as widespread altered connectivity degrees in many brain areas. We observed clinical improvement in OCD patients after 16 weeks of SSRI treatment, which was accompanied by significantly elevated small-world efficiency, modular organization, and connectivity degree. Improvement of obsessive-compulsive symptoms was significantly correlated with changes in connectivity degree in right ventral frontal cortex in OCD patients after treatment. Conclusions: This is first study to use graph-theory approach for investigating valuable biomarkers for the effects of SSRI on neuronal circuitries of OCD patients. Our findings suggest that OCD phenomenology might be the outcome of disrupted optimal balance in the brain networks and that reinstating this balance after SSRI treatment accompanies significant symptom improvement.