The multimodal neuroimaging signatures and gene expression profiles for adverse childhood experiences

Adverse childhood experiences (ACEs) have been considered significant drivers of negative mental health and cognitive outcomes. However, identifying clear neurobiological signatures of ACEs has been challenging due to limited sample sizes, participant heterogeneity, and methodological variability.

A whole-brain meta-analysis was conducted to identify functional, structural, and overlapping brain alterations in ACEs-exposed individuals compared to unexposed controls, using a large sample (functional analysis: 63 studies, 3549 participants; structural analysis: 38 studies, 2919 participants). Subgroup analyses were performed based on age, adversity type, diagnostic status, and functional magnetic resonance imaging task domains, providing a more nuanced aspect of ACEs' effect on neurodevelopment. Furthermore, the BrainMap-derived task activation maps, atlas-based nuclear imaging-derived neurotransmitter maps, and postmortem gene expression profiles were integrated to examine spatial correlations between ACEs-related brain abnormalities and downstream behavioral processes, disease domains, and upstream receptor/transporter distributions and gene expression.

ACEs-exposed individuals exhibited significantly increased functional activity in the amygdala, increased gray matter volume (GMV) in the parahippocampal gyrus, and reduced GMV in the inferior frontal gyrus and supramarginal gyrus, with overlapping abnormalities observed in the parahippocampal gyrus. Subgroup analyses revealed distinct brain alterations. Furthermore, specific associations were identified between structural alterations and the distribution of dopaminergic, serotonergic, and GABAergic neurotransmitter systems. Enrichment analyses further emphasized the profound impact of ACEs on neurodevelopment, immunometabolism, and psychopathological trajectories.

These findings characterize the neural substrates of ACEs, providing valuable insights into their impact on neurodevelopment and suggesting potential targets for ACEs-related disorders.