Occipital connectivity networks mediate the neural effects of childhood maltreatment on depressive symptoms in major depressive disorder

Childhood maltreatment (CM) is a well-established risk factor for major depressive disorder (MDD). The neural mechanisms linking childhood maltreatment experiences to changes in brain functional networks and the onset of depression are not fully understood. In this study, we enrolled 66 patients with MDD and 31 healthy controls who underwent resting-state fMRI scans and neuropsychological assessments. We employed multivariate linear regression to examine the neural associations of CM and depression, specifically focusing on the bilateral occipital functional connectivity (OFC) networks relevant to MDD. Subsequently, a two-step mediation analysis was conducted to assess whether the OFC network mediated the relationship between CM experiences and the severity of depression. Our study showed that patients with MDD exhibited reduced OFC strength, particularly in the occipito-temporal, parietal, and premotor regions. These reductions were negatively correlated with CM scores and the severity of depression. Notably, the overlapping regions in the bilateral OFC networks, affected by both CM experiences and depressive severity, were primarily observed in the bilateral cuneus, left angular and calcarine, as well as the right middle frontal cortex and superior parietal cortex. Furthermore, the altered strengths of the OFC networks were identified as positive mediators of the impact of CM history on depression symptoms in patients with MDD. We have demonstrated that early exposure to CM may increase vulnerability to depression by influencing the brain's network. These findings provide new insights into understanding the pathological mechanism underlying depressive symptoms induced by CM. •CM is connected to MDD through changes in occipital functional connectivity (OFC) networks.•MDD patients show reduced OFC strength, linked to CM and depression severity in specific brain regions.•The OFC mediates the effect of CM on depressive symptoms in MDD patients, revealing underlying neural mechanisms.