Dopamine dysfunction beyond psychosis: Reevaluating its role in depression, anxiety, and obsessive-compulsive...

Dopaminergic dysfunction has traditionally been associated with psychotic disorders. However, emerging evidence implicates dopamine in a broader range of psychiatric conditions. This review critically reexamines dopamine's role beyond psychosis, focusing on major depressive disorder, anxiety disorders, and obsessive-compulsive disorder (OCD)-three high-burden conditions where current treatments remain suboptimal for many patients. This review is conducted to synthesise and critically evaluate the evidence for dopamine dysfunction as a transdiagnostic mechanism underpinning core symptom domains across depression, anxiety, and OCD. Consistent patterns of dopamine dysregulation were identified in mesolimbic and mesocortical pathways, as well as the cortico-striatal-thalamo-cortical (CSTC) loop. Common symptom dimensions-such as anhedonia, apathy, compulsivity, and cognitive inflexibility-were linked to region-specific dopamine deficits. Furthermore, gene-environment interactions and inflammation-induced suppression of dopamine emerged as shared etiological factors. Dopaminergic agents (e.g., bupropion, pramipexole, aripiprazole), neuromodulatory approaches (e.g., TMS, DBS), and biomarker-guided interventions showed promise, particularly in treatment-resistant or subtype-specific presentations. Dopamine dysfunction is a core, transdiagnostic mechanism in depression, anxiety, and OCD, affecting key circuits involved in reward, motivation, and cognitive control. Integrating dopaminergic biomarkers and interventions into psychiatric care may facilitate personalised treatment and improve clinical outcomes.