Neural mechanisms underlying exposure and response prevention for obsessive compulsive disorder: A randomized...

Fear extinction is an important treatment target of obsessive-compulsive disorder (OCD). In the current randomized controlled trial, we examined the therapeutic modulation of exposure and response prevention (ERP) on neural activation during fear extinction in OCD to identify mechanisms of action and response biomarkers.

Thirty-four patients with OCD were randomized to either 12-weeks of ERP or a waitlist. Before, during, and 12-weeks after treatment, patients were assessed using functional magnetic resonance imaging (fMRI) during a 2-day fear extinction paradigm. Neural activation was examined in disease- and construct-relevant circuits and nodes (n = 18).

The ERP group had a significant reduction in OCD severity compared to waitlist. A voxel-wise GLM analysis of fMRI data revealed clusters of ERP > waitlist activation during fear conditioning (bilateral dorsal amygdala and right hippocampus) and extinction (right ventrolateral prefrontal cortex, located within the salience network). These changes in activation did not correlate with OCD severity changes, however. In contrast, we observed that a reduction in the activation of the left supramarginal gyrus (in the executive control network) during extinction recall correlated with OCD symptom improvement, suggesting a possible role as a response biomarker.

This study highlights the relevance of a dimensional approach (e.g., focused on fear extinction) for biomarker discovery in neuropsychiatry, provides insights into the mechanisms of action of ERP in OCD, and identifies a potential treatment target in the parietal cortex that could support the biomarker-driven development of novel therapies (e.g., brain stimulation protocols), including combination treatments with ERP.

NCT02467374.