Serotonergic underpinnings of obsessive‐compulsive disorder: A systematic review and meta‐analysis of neuroimaging findings
Year: 2024
Type: review
Study designs: Systematic Review, Meta-Analysis
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.
DOI: 10.1111/pcn.13760
Institutions: Centre Hospitalier Universitaire de Nîmes, University of Geneva, Centre National de la Recherche Scientifique, Inserm, Université Paris-Est Créteil, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Institut du Cerveau, Hôpital Albert-Chenevier, Universidade de Santiago de Compostela, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: Eli Lilly and Company, H. Lundbeck A/S
OpenAlex ID: W4404160271