Obsessive-Compulsive Disorder: Comorbidity, Biomarkers, Circuits, and Treatment Strategies

Obsessive-compulsive disorder (OCD), characterized by intrusive thoughts and repetitive behaviors, frequently co-occurs with anxiety disorders, contributing to greater diagnostic complexity, more severe symptoms, and poorer treatment outcomes. In this review, we consider OCD in the context of its comorbidity with anxiety and examine evidence that the two conditions may share genetic, neurochemical, and circuit-level vulnerabilities. Particular attention is given to the cortico-striato-thalamo-cortical, frontoparietal, and frontolimbic networks, which may interact to form a self-reinforcing cycle in which anxiety intensifies OCD symptoms, while compulsive behaviors provide transient relief but may ultimately maintain pathological patterns of brain activity. We also discuss how these shared mechanisms may shape current and emerging treatment strategies, including pharmacological approaches targeting serotonergic, glutamatergic, dopaminergic, and histaminergic systems, cognitive-behavioral interventions, and neuromodulation techniques such as deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound. We further consider major depressive disorder and posttraumatic stress disorder as additional examples of psychiatric comorbidity, with overlapping neural substrates and clinical features. Taken together, these findings suggest that considering comorbidity alongside core OCD symptoms may improve our understanding of its pathophysiology, help identify clinically relevant biomarkers, and support individualized treatment, while providing a broader transdiagnostic perspective on psychiatric disorders.