Childhood adversity, stress reactivity, and structural brain measures in stress-related/neurodevelopmental disorders, and their comorbidity: A large transdiagnostic cross-sectional study.

Childhood adversity (CA), including childhood adverse life events, increases the risk for development of psychiatric disorders later in life. Both CA and psychiatric disorders are associated with structural brain changes and dysfunctional hypothalamic-pituitary-adrenal-axis. However, many studies investigated single diagnostic and single regions of interest of the brain, and did not take stress reactivity into account. We investigated associations of CA and cortisol levels with gray matter volume and cortical thickness, in a whole-brain manner. Primary analysis constituted of a transdiagnostic approach, followed by a moderation analysis to investigate the influence of diagnosis. Patients with stress-related and/or neurodevelopmental disorders and matched healthy controls underwent an magnetic resonance imaging scan, next to assessing hair cortisol levels and CA/life events. CA was reported by 62-72% of the patients versus 33% of the controls. Primary transdiagnostic linear regression analyses revealed that CA was not associated with gray matter volume, while childhood life events were associated with lower right thalamic volume. Hair cortisol was not associated with any lobe volume. None of the associations were moderated by diagnosis. In conclusion, CA is a risk factor that needs to be taken into account when investigating psychiatric disorders. Yet the relationship with structural brain changes and stress reactivity is less clear than postulated on the basis of more seed-based studies.