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We systematically reviewed the literature to provide a quantitative assessment of the role of serotonin (5\u2010HT) in patients with untreated OCD through imaging. We searched for neuroimaging studies investigating central 5\u2010HT tonus in unmedicated patients with OCD, excluding studies comprising treated patients to prevent bias from antidepressant\u2010induced changes in serotonergic tonus. We also conducted a meta\u2010analysis using a homogeneous group of positron emission tomography and single photon emission computed tomography articles that compared 5\u2010HT transporter (SERT) and 5\u2010HT2A 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\u2010analysis. Risk of bias was assessed by a revised form of the Newcastle\u2010Ottawa Scale. We provided standardized mean difference (SMD) values for SERT and 5\u2010HT2AR binding potential measures across 15 different brain regions. Patients with OCD showed lower SERT binding potential in the brainstem (SMD\u2009=\u2009\u22121.13,\u00a095% CI [\u22121.81 to \u22120.46]), midbrain (SMD\u2009=\u2009\u22120.54, 95% CI [\u22120.92 to \u22120.16]), and thalamus\/hypothalamus regions (SMD\u2009=\u2009\u22120.58, 95% CI [\u22120.99 to \u22120.18]) 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\u2010HT system dysfunction. However, the exact mechanisms underlying this phenotype remain elusive. The limitations include heterogeneity across studies in populations, imaging techniques, and radiotracer usage.<\/jats:p>","DOI":"10.1111\/pcn.13760","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:29:43Z","timestamp":1731025783000},"page":"48-59","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Serotonergic underpinnings of obsessive\u2010compulsive disorder: A systematic review and meta\u2010analysis of neuroimaging findings"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-9847","authenticated-orcid":false,"given":"Martin","family":"Pastre","sequence":"first","affiliation":[{"name":"Department of Psychiatry CHU Nimes  Nimes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob\u2010Val\u00e9ry","family":"Occ\u00e9an","sequence":"additional","affiliation":[{"name":"Laboratoire de Biostatistique, 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