Effects of childhood trauma experience and BDNF Val66Met polymorphism on brain plasticity relate to emotion regulation.

Abstract Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may modulate the link between childhood trauma experience and psychopathology by altering trophic signaling on neuroplasticity. However, few multimodal magnetic resonance imaging (MRI) researches have investigated this gene-environment interaction on both structural and functional plasticity, thereby advancing knowledge about the etiology, prevention, and customized therapeutic directions of mental disease in individuals with childhood trauma experience. We recruited a large non-clinical sample of young adults that completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal MRI scans, and genotyping. Morphometric similarity network (MSN) and independent component analysis were adopted to quantify brain structural and functional changes. Gene-environment-brain-behavior relationships were identified by multiple regression and mediation effect analysis. CTQ score was positively associated with depression and anxiety scores. We found interactions on MSN in sensorimotor, temporal, and orbitofrontal cortex. For intra-network connectivity, significant interaction was noted in clusters within sensorimotor network. For inter-network connectivity, connectivity between dorsal attention network and salience network showed an interactive effect. For mean connectivity strength of each network, we found a main effect of CTQ score on self-reference network that was an outstanding mediator supporting the relationship between CTQ score and anxiety. Our findings demonstrate that childhood trauma and the BDNF Val66Met polymorphism are associated with brain plasticity involving emotion regulation, structurally and functionally, which may contribute to understanding psychotic mechanisms and predicting differential susceptibility. Imaging genetics may be useful as biomarkers to provide early assessment and guide cognitive interventions to avoid or decrease the risk of developing psychopathology.