306. Genetic and neuroimaging correlates of symptom severity in major depressive disorder: an imaging–genetics study

Abstract

Abstract Background The habenula is a key region involved in mood and sleep regulation and is critically implicated in major depressive disorder (MDD). Aims & Objectives This imaging–genetics study aimed to characterize the relationships among genetic variation, habenula-centered brain connectivity, and clinical features of depression in MDD. Method Ten candidate genes related to mood and circadian rhythm were genotyped in patients with MDD and healthy controls. All participants underwent 3T structural and resting-state functional MRI. Structural and functional connectivity between the habenula, septal nuclei, and other brain regions were analyzed. Imaging-genetic analyses focused on seed-based connectivity, including functional correlations and structural connectivity. Results Sixty-nine patients with MDD and forty-one healthy controls of Korean ethnicity were included in the analysis. In MDD, structural connectivity between the left habenula and the left inferior frontal gyrus was significantly associated with rs2304672, and connectivity between the left habenula and the right ventral anterior thalamic nucleus was associated with rs7123390. Across all participants, functional connectivity between the left habenula and right parahippocampal gyrus showed consistent significant associations with multiple symptom domains, including depression and sleep disturbance. Discussion & Conclusions This study identified two significant imaging–genetics associations involving the habenula in MDD and demonstrated that habenula-related functional connectivity correlated with clinical symptoms across participants. These findings indicate that individual variations in habenula-centered circuits are partly shaped by gene polymorphisms related to mood and circadian regulation and contribute to the symptom heterogeneity of depression.