Default Mode Network Alterations Induced by Childhood Trauma Correlate With Emotional Function and SLC6A4 Expression

As one of the most studied resting-state functional networks, default mode network (DMN) is related to pathogenesis in neuropsychiatry. However, it is unclear whether changed DMN connectivity is transformed into vulnerability to psychopathology in adults who experienced childhood trauma, and what is the underlying genetic basis. Exploring the effect of DMN on environment-behavior pathway and the related genetic modulation mechanisms could further a better understanding of psychiatric pathogenesis and early prevention strategy. Two hundred and sixteen young adults with varying levels of early trauma indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from the community. Static and dynamic functional connectivity based on DMN seeds and independent component analysis based on whole-brain voxels were combined to explore DMN alterations related to the CTQ score. Relationships between CTQ score, DMN connectivity, and behavioral scores were confirmed by mediation effect analysis. Imaging-genomic correlations were further used to identify risk genes whose expression was associated with the DMN changes. Dysregulated DMN connectivity was found both in seed-level and voxel-level analyses. Moreover, the functional disruption in the left temporal pole, right parahippocampal gyrus, and frontoparietal connectivity mediated the effects of childhood trauma on emotional behavior. The serotonin transporter gene was identified and might suggest the biological underpinning of the relationship between childhood trauma, DMN, and emotion regulation. Changed DMN may be useful as biomarkers to provide a powerful supplement to psychological evaluation related to childhood trauma. Combined with gene expression profiles, our findings advance a more integrative understanding of DMN alterations induced by childhood trauma, and clarify its implications for psychiatric pathogenesis and early prevention strategies.