Molecular mechanisms and behavioral relevance underlying neural correlates of childhood neglect.

ABSTRACT

BACKGROUND: Childhood neglect is associated with brain changes, yet the molecular mechanisms and behavioral relevance underlying such associations remain elusive. METHODS: We calculated fractional amplitude of low-frequency fluctuations (fALFF) using resting-state functional MRI and tested their correlation with childhood neglect across a large sample of 510 healthy young adults. Then, we investigated the spatial relationships of the identified neural correlates of childhood neglect with gene expression, neurotransmitter, and behavioral domain atlases. RESULTS: We found that more severe childhood neglect was correlated with higher fALFF in the bilateral anterior cingulate cortex. Remarkably, the identified neural correlates of childhood neglect were spatially correlated with expression of gene categories primarily involving neuron, synapse, ion channel, cognitive and perceptual processes, and physiological response and regulation. Concurrently, there were significant associations between the neural correlates and specific neurotransmitter systems including serotonin and GABA. Finally, neural correlates of childhood neglect were associated with diverse behavioral domains implicating mental disorders, emotion, cognition, and sensory perception. LIMITATIONS: The cross-sectional study design cannot unequivocally establish causality. CONCLUSIONS: Our findings may not only add to the current knowledge regarding the relationship between childhood neglect and mental health, but also have clinical implications for developing preventive strategies for individuals exposed to childhood neglect who are at risk for mental disorders.