A Neurocircuit–Molecular Pathway Framework for Psychiatric Classification: Clinical and Translational Implications

Abstract

Contemporary psychiatric diagnostic systems are predominantly symptom-based, contributing to substantial heterogeneity within diagnostic categories, frequent comorbidity, and limited guidance for mechanism-based treatment. Advances in neuroscience increasingly indicate that psychiatric disorders arise from dysfunction within specific neurocircuits, modulated by molecular and cellular pathways. However, these insights remain insufficiently integrated into clinical classification. In this article, we propose a neurocircuit–molecular pathway–based framework intended to complement existing diagnostic systems. The framework assigns individuals to dominant dysfunctional neurocircuits and associated molecular pathways, supported by graded levels of clinical and neurobiological evidence. Using schizophrenia spectrum disorders, bipolar disorder, and obsessive–compulsive and addictive disorders as exemplars, we illustrate how this approach may account for clinical heterogeneity, overlapping symptom dimensions, and differential treatment response. We further discuss implications for mechanism-informed pharmacological and neuromodulatory interventions, as well as for research stratification and future validation. While acknowledging current limitations in biomarker availability and circuit specificity, this framework provides a clinically interpretable and scalable approach to integrating neuroscience into psychiatric classification.