Altered Reward Circuit Function Moderates the Relationship between Childhood Maltreatment and Depression Severity in Adolescents

Abstract

Background. The role of childhood maltreatment (CM) is believed to be crucial in the aberrant function of reward circuit in adolescent-onset major depressive disorder (AO-MDD). Nevertheless, the impact of abnormalities in the GP-based reward circuit on the association between CM and the severity of AO-MDD remains largely unknown. Methods. The GP-based resting-state functional connectivity (RSFC) was analyzed in a sample of 75 patients with AO-MDD and 80 healthy controls in order to identify potential abnormalities in the GP-based reward circuit in AO-MDD patients. Furthermore, we investigated the possible associations between aberrant GP-based reward circuit functioning, CM and its subtypes (namely, childhood abuse and childhood neglect), and the severity of AO-MDD. Results. Compared to the healthy control group, patients with AO-MDD demonstrated a reduction in RSFC between the left posterior GP and the right dorsomedial prefrontal cortex (DMPFC). Our moderation analysis revealed that the abnormal RSFC between the posterior GP and DMPFC had a moderating effect on the relationship between CM and the severity of AO-MDD. Furthermore, upon further interaction decomposition, we observed a positive correlation between CM and AO-MDD severity exclusively in patients with AO-MDD who exhibited lower RSFC between the posterior GP and DMPFC. For AO-MDD patients with higher RSFC between posterior GP and DMPFC, the relationship between CM and AO-MDD severity was not discernible. Conclusions. Our findings underscore the crucial role of anomalies in the reward circuit in AO-MDD and furnish novel leads for probing the relationship among CM, malfunctioning of the reward circuit, and AO-MDD.