Neuroimaging alterations in relatives of patients with obsessive-compulsive disorder: A review of magnetic resonance imaging studies

Background: Obsessive-Compulsive Disorder (OCD) demonstrates substantial heritability, implicating a genetic contribution to its pathophysiology. Neuroimaging studies of unaffected first-degree relatives offer insight into the neurobiology of the disorder. Methods: A systematic search of PubMed, Web of Science, and Scopus was conducted in August 2024 to identify Magnetic Resonance Imaging (MRI) studies comparing unaffected relatives of individuals with OCD to healthy controls. Significant findings were reported based on patterns of brain changes in individuals with OCD and their relatives. Results: A total of 32 studies were reviewed, including 18 functional MRI, 8 structural MRI, and 7 diffusion tensor imaging studies. Despite inconsistencies arising from heterogeneity in imaging modalities, age groups, and analytic methods, certain regions and patterns emerged repeatedly. Results were grouped into four clusters. Cluster 1, the most consistently reported, involved shared or intermediate alterations in relatives, suggesting putative endophenotypes. Frequently implicated regions included the insula, thalamus, dorsolateral and ventromedial prefrontal cortices, and parietal cortex. Cluster 2 described more pronounced alterations in relatives than in OCD patients, often in frontoparietal regions, possibly reflecting preclinical vulnerability or protective features. Cluster 3 showed opposite trends in relatives, particularly in occipital and parietal regions, which may indicate compensatory or protective processes. Although very few, there were some findings that were specific to relatives (cluster 4). Conclusion: This review identifies neuroimaging findings in unaffected relatives of individuals with OCD. Most studies suggest potential endophenotypes, with some reflecting compensatory mechanisms. These findings support further research to validate the proposed clusters and clarify heritable neural markers of OCD.