Abstract
Obsessive‐compulsive disorder (OCD) is a frequent and disabling condition, with many patients being treatment‐resistant. Improved understanding of its neurobiology is vital for better therapies. Evidence is still conflicting regarding specific serotonergic‐related dysfunctions in OCD. We systematically reviewed the literature to provide a quantitative assessment of the role of serotonin (5‐HT) in patients with untreated OCD through imaging. We searched for neuroimaging studies investigating central 5‐HT tonus in unmedicated patients with OCD, excluding studies comprising treated patients to prevent bias from antidepressant‐induced changes in serotonergic tonus. We also conducted a meta‐analysis using a homogeneous group of positron emission tomography and single photon emission computed tomography articles that compared 5‐HT transporter (SERT) and 5‐HT2A receptor (HT2AR) binding potential in different brain regions of patients with untreated OCD and healthy controls. The systematic review encompassed 18 articles, with 13 included in the subsequent meta‐analysis. Risk of bias was assessed by a revised form of the Newcastle‐Ottawa Scale. We provided standardized mean difference (SMD) values for SERT and 5‐HT2AR binding potential measures across 15 different brain regions. Patients with OCD showed lower SERT binding potential in the brainstem (SMD = −1.13, 95% CI [−1.81 to −0.46]), midbrain (SMD = −0.54, 95% CI [−0.92 to −0.16]), and thalamus/hypothalamus regions (SMD = −0.58, 95% CI [−0.99 to −0.18]) with neglectable to moderate heterogeneity. By combining results from 2 decades of molecular imaging studies, we show that individuals with OCD exhibit lower SERT binding potential in specific brain regions, providing compelling evidence of a 5‐HT system dysfunction. However, the exact mechanisms underlying this phenotype remain elusive. The limitations include heterogeneity across studies in populations, imaging techniques, and radiotracer usage.