Abstract
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.
Highlights
The brain’s “default mode network” (DMN) is a popular and rapidly growing neuroscientific topic of mental health
Based on mRNA gene expression profiles derived from the Allen Human Brain Database (ABA) [21, 22], we identified risk genes whose expression was associated with the DMN changes
We found that the Childhood Trauma Questionnaire (CTQ) score was positively correlated with the state anxiety score (β = 0.356, p < 0.001, t = 5.572), trait anxiety score (β = 0.346, p < 0.001, t = 5.523), Beck Depression Inventory (BDI) score (β = 0.289, p < 0.001, t = 4.419), and harm avoidance (HA)
Summary
The brain’s “default mode network” (DMN) is a popular and rapidly growing neuroscientific topic of mental health. During the sensitive period of brain-development, early trauma experience can act as life stressor and produce a series of hormonal changes and physiological reactions, which may cause permanent modification to neural structure and function [9, 10], including DMN regions. The relationship between early trauma, disturbances in DMN regions, and psychopathology has been uniformly confirmed [11,12,13,14]. Neuroimaging studies highlight the functional plasticity of DMN during the early sensitive or critical periods [8, 15], and support the model of dysregulated DMN connectivity in early life trauma and related negative affect states. Preclinical studies are critical for understanding the relationship between DMN, childhood trauma, and risk of mental illness
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