The brain’s hemodynamic response function rapidly changes under acute psychosocial stress in association with genetic and endocrine stress response markers

Significance Understanding how stress predisposes for psychopathology requires the identification of physiological stress-regulatory mechanisms with pathogenic potential. Here, we applied fMRI to investigate the interaction between acute psychosocial stress and the brain’s hemodynamic response function (HRF). The HRF models how local neural activity elicits cerebral blood flow changes, spanning several biophysical processes including neurovascular coupling (NVC). Stress replicably shifted the HRF peak in temporal, insular, and prefrontal brain regions, moderated by functional variants of KCNJ2 , a protein involved in NVC. Hippocampal HRF markers correlated with the cortisol response and genetic variants that reflect transcriptional responses to glucocorticoids and the risk for depression. We suggest that acute psychosocial stress modulates hemodynamic response properties which could lead to previously undescribed endophenotypes of stress-related disorders.