Why the body matters in major depressive disorder: neuroimaging findings of somatic symptoms and ongoing challenges.

Abstract

With growing recognition that somatic symptoms constitute a clinically significant yet underexplored dimension of major depressive disorder (MDD), symptoms including sleep disturbances, gastrointestinal discomfort, pain, appetite changes, and fatigue have attracted increasing research attention. These symptoms are not only highly prevalent but are also closely associated with poor prognosis, treatment resistance, and elevated suicide risk. In this context, neuroimaging studies of the somatic manifestations of MDD have provided critical insights to advance precision diagnosis and individualized intervention. This review comprehensively integrates functional and structural neuroimaging findings on discrete somatic symptoms and somatic symptom clusters in MDD. It identifies the specific neural circuit abnormalities associated with individual symptom domains while elucidating shared pathophysiological mechanisms across symptom types, including disrupted interoceptive processing, pathological default mode network activity, and impaired sensory gating. On this basis, the review discusses the therapeutic and predictive implications of these findings and proposes future research directions oriented toward network-based brain-symptom mapping, transdiagnostic and longitudinal designs, and multimodal multilevel integration. By synthesizing existing evidence, this review provides a framework for understanding the neural substrates of somatic symptoms in MDD, developing somatic phenotype-based biomarkers and targeted neuromodulation therapies, and integrating systems-level neuroimaging into precision psychiatry to advance biologically informed diagnosis/treatment.