Mismatch or allostatic load? Timing of life-adversity differentially shapes gray matter volume and anxious-temperament

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease-development, a hypothesis that has not yet been tested explicitly in humans.We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N=833) and brain morphology (N= 129).Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modelling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator.Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.