Genetic Underpinnings of Obsessive–Compulsive Disorder With and Without Tics: Implications of Genetic Heterogeneity on Clinical Management

The exact genetic mechanisms and link between obsessive-compulsive disorder (OCD) and tics/Tourette syndrome are not fully understood. This narrative review aims to summarize the literature examining whether the clinical phenotypes of OCD and OCD + tics (tic-related OCD) represent distinct entities and how this relates to their genetic underpinnings. Systematic searches were conducted in MEDLINE Complete and Embase databases to identify studies published since the Diagnostic and Statistical Manual 5th Edition introduced the category of OCD with and without tics in 2013. Articles reporting on family cohort studies, linkage and epigenetic analyses, and genome-wide association studies involving patients with OCD and/or tic-related OCD were included. While the studies have highlighted significant genetic heterogeneity, there is some evidence to suggest the role of serotonergic, glutamatergic, and dopaminergic systems, with the latter playing a significant role in the genesis of tic spectrum symptoms, which may have implications for choice of pharmacological management in those with OCD + tics. Given the significant genetic heterogeneity and consequent phenotypic variations, future research delineating homogeneous subgroups is needed, including longitudinal studies that examine whether the clinical phenotypes of the OCD/tic spectrum of conditions "breed true" in offspring, which may have implications for clinical assessment and management.