Compulsive Disorder: Understanding of the Pathophysiology and Therapeutic Implications

Dear Colleagues,

Compulsive phenomena cut across traditional diagnostic boundaries and coalesce around a narrowed repertoire of overlearned responses, sustained by dysregulation within cortico-striato-thalamo cortical loops and by alterations in cognitive control, valuation, and habit mechanisms, a framework that invites mechanistic inquiry and translational ambition alike. Building on convergent evidence from circuit mapping, computational modeling, and neurochemistry, with glutamatergic, dopaminergic, and neuroimmune signals repeatedly implicated, contemporary research is beginning to link cellular and synaptic perturbations to systems-level biomarkers and to clinically observable rigidity in thought and behavior, thereby refining targets for both pharmacologic modulation and neuromodulatory intervention. At the same time, a transdiagnostic perspective on compulsivity encourages the integration of obsessive–compulsive disorder with related conditions and behaviors, allowing shared pathways to be tested against developmental trajectories, comorbidity patterns, and treatment response, and fostering the search for predictors that can guide personalization across the lifespan. This Special Issue seeks work that advances understanding from molecules to networks to patients, and that connects pathophysiology to therapeutic implications, including optimization of exposure-based psychotherapy, augmentation strategies aimed at glutamate and inflammation, and precision approaches to brain stimulation that translate circuit knowledge into durable clinical benefit.

Prof. Dr. Donatella Marazziti
Guest Editor

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