Serotonin (5-HT) Signaling in Obsessive-Compulsive Disorder (OCD)
Serotonin is the neurotransmitter most closely linked to OCD based on consistent pharmacologic evidence showing symptom improvement with serotonin reuptake–targeting agents. [1]
Pharmacologic Evidence Linking Serotonin to OCD
Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy for OCD compared with placebo in adults. [1] Clomipramine, which has strong serotonergic effects, has also been historically central to serotonergic hypotheses for OCD treatment response. [2]
Neurotransmitter-System Framework
OCD neurobiology is most consistently connected to cortico-striato-thalamo-cortical circuits that include serotonin signaling. [3] Multiple neurotransmitter systems have been studied in OCD, but serotonergic mechanisms have the most direct support from treatment pharmacology. [3]
Monotherapy Versus Combination Approaches
Serotonin reuptake–targeting pharmacotherapy is typically used as foundational treatment in OCD, including SSRI monotherapy. [1] Augmentation strategies that modify additional neurotransmitter systems are used for incomplete response, but core pharmacologic targeting remains serotonergic. [1]
Clinical Implications of the Serotonin Link
Clinical response to SSRIs supports a serotonergic mechanism for OCD symptom reduction. [1] Serotonergic involvement is supported by neuropharmacology and mechanistic reviews describing serotonergic hypotheses for OCD. [2]
Practical Clarification on “Most Closely Linked”
Evidence does not support a single neurotransmitter as the sole cause of OCD. [3] Nonetheless, serotonin remains the most directly implicated neurotransmitter by the therapeutic efficacy of serotonergic agents. [1]