OBSESSIVE-COMPULSIVE DISORDER: CIRCUIT-LEVEL PATHOPHYSIOLOGY AND CLINICAL MANIFESTATIONS
Keywords:
Keywords: Obsessive-compulsive disorder, Cortico-striato-thalamo-cortical circuit, Orbitofrontal cortex, Caudate nucleus, Habit formation, Deep brain stimulationAbstract
Abstract: Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by intrusive, distressing thoughts (obsessions) and repetitive behaviors or mental acts (compulsions) performed to reduce the anxiety these thoughts provoke. Neuroimaging and lesion studies consistently implicate hyperactivity within cortico-striato-thalamo-cortical (CSTC) circuits, particularly loops connecting the orbitofrontal cortex, anterior cingulate cortex, caudate nucleus, and thalamus. Symptom provocation studies demonstrate that this hyperactivity intensifies during active symptom states and normalizes following effective treatment. At the cellular and network level, OCD is associated with imbalance between direct and indirect striatal pathways favoring net cortical excitation, dysregulated glutamatergic and serotonergic signaling, and a shift from goal-directed to habitual behavioral control mediated by relative hyperactivity of the dorsolateral striatum. While selective serotonin reuptake inhibitors and exposure-based cognitive behavioral therapy remain first-line treatments, refractory cases increasingly respond to deep brain stimulation targeting specific nodes within these circuits. This review summarizes the neuroanatomical organization of CSTC loops, the cellular and network mechanisms underlying OCD pathophysiology, circuit correlates of specific symptom dimensions, and clinical and neuromodulatory implications.
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