OCD: Serotonergic mechanisms

Obsessive-compulsive disorder (OCD) is typically treated with selective serotonin- reuptake inhibitors (SSRIs), cognitive behavioral therapy (CBT), or both. The neurobiological effects of these treatments that are associated with symptom improvement, however, remain unclear. The neurotransmitter serotonin has been implicated in OCD pathology, including in brain circuits contained in corticostriato- thalamic loops; yet, there is no consensus in the literature over a particular underlying serotonergic mechanism in OCD. Recent studies have used the α-[ ¹¹C]methyl-L-tryptophan tracer coupled with positron emission tomography (PET) to estimate brain regional serotonin synthesis capacity in OCD patients in vivo. Regions that exhibited elevated serotonin synthesis in symptomatic OCD, relative to healthy controls, demonstrated a paradoxical and further increase during treatment with CBT or SSRI, parallel to symptomatic improvement. This suggests that serotonin engagement may be an attempt at inhibiting symptoms at baseline, albeit unsuccessfully, and that “braking” or “resistance” might gradually become more effective, and eventually successful, with the help of adapted behavioral interventions and/or SSRIs.