Brain network controllability in genetic risk, childhood abuse, and adult anxiety

<b>Background:</b> Network control theory can quantify controllability to evaluate how altered transitions between brain states contribute to cognitive, emotional, and behavioural challenges. Childhood abuse, influenced by genetics, is associated with disrupted network function, though the exact control processes are not yet understood.<b>Objective:</b> This study aims to investigate the association between brain network controllability and childhood abuse experiences, and to elucidate its potential mediating role in the relationship among polygenic risk scores (PRS) for childhood abuse, childhood abuse experiences, and adult health outcomes.<b>Methods:</b> This study measured the controllability of functional brain networks, including both average and modal controllability, in a cohort of 214 young adults with varied histories of childhood abuse. Participants also completed psychological assessments, whole-exome sequencing, and the calculation of PRS for childhood abuse. This study investigate the association between brain network controllability and childhood abuse. Furthermore, a mediation model was performed to explore the potential mediating role of brain network controllability in the relationship between genetic risk, childhood abuse experiences, and adult health outcomes.<b>Results:</b> The controllability of the dorsal attention and sensorimotor networks, as well as the controllability of key ROIs within the sensorimotor, default mode, dorsal attention, visual, and control networks, demonstrated significant correlations with abuse scores. Despite no direct correlation between PRS and self-reported childhood abuse, indirect effects through the controllability of visual and control network regions were identified. The controllability of the left postcentral gyrus in the dorsal attention network mediated the relationship between childhood abuse and adult anxiety.<b>Conclusions:</b> This study reveals that brain network controllability is a pivotal factor, not only bridging PRS and childhood abuse but also serving as a potential mediator between childhood trauma and adult anxiety, offering a new perspective on the neurobiology of childhood abuse-related psychopathology.