Toward a Dopaminergic–Serotoninergic–Noradrenergic Dysregulation Disorder (DSNDD): A Neurobiological Reframing of Affective Polarity

Current psychiatric nosology defines bipolar disorder through descriptive phe-nomenology rather than established neurobiological mechanisms. Despite decades ofresearch, increasing evidence implicates dysregulation across dopaminergic, seroton-ergic, and noradrenergic systems in the pathophysiology of affective polarity states.This article proposes a theoretical reframing termed Dopaminergic–Serotoninergic–NoradrenergicDysregulation Disorder (DSNDD), conceptualized as a systems-level instability ofmonoaminergic modulation across cortico-limbic circuits. Drawing on neurochem-ical, genetic, circadian, and neuroimaging evidence, this framework aims to inte-grate the monoamine hypothesis of mood disorders [1] with contemporary modelsof dopaminergic sensitization in mania [2] and network dysregulation theories ofbipolar disorder [3]. Rather than replacing existing diagnostic categories, DSNDDis proposed as a mechanistic dimensional model to guide biomarker developmentand precision psychiatry approaches.