Altered Brain Functional Connectivity and Peripheral Transcriptomic Profiles in Major Depressive Disorder With Childhood Maltreatment

<b>Background:</b> Childhood maltreatment (CM) is a significant risk factor for major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. This study aimed to investigate brain functional networks and peripheral transcriptomics in patients with MDD who have a history of CM. <b>Methods:</b> Functional imaging data were collected and network-based statistics were used to identify differences in functional networks among MDD patients with CM (MDD_CM, <i>n</i> = 78), MDD patients without CM (MDD_nCM, <i>n</i> = 61), and healthy controls (HC, <i>n</i> = 126). Additionally, blood transcriptional data were clustered into co-expression modules, and module differential connectivity analysis was utilized to assess variations in gene co-expression network modules among the groups. <b>Results:</b> The results revealed a significant difference in an inferior occipital gyrus-centered functional network among the three groups. Furthermore, eight gene co-expression modules differed among the groups and were enriched in multiple branches related to immune responses or metabolic processes. Notably, a module enriched in type I interferon-related signaling pathways demonstrated a significant correlation with the disrupted network in the MDD_nCM group. Moreover, multiple immune-related gene modules were found to be significantly correlated with sleep disturbances in MDD_CM patients. <b>Conclusions:</b> Dysregulation of an inferior occipital gyrus-centered functional network and immune-related transcriptomic alterations significantly associate with the pathophysiology of MDD_CM.