An fMRI study examining effects of acute D-cycloserine during symptom provocation in spider phobia

Background: Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations. Methods: Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli. Results: In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group. Conclusions: Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.