Functional Brain Network Dynamics Mediate the Relationship between Female Reproductive Aging and Perceived Hostility: Relevance to Neuropsychiatric Disorders

Premature reproductive aging is linked to heightened stress sensitivity and psychological maladjustment across the life course. However, the brain dynamics underlying this relationship are poorly understood. To address this issue, we analysed multimodal data from female participants in the Adolescent Brain and Cognitive Development (longitudinal, N=441; aged 9-12 years) and Human Connectome-Aging (cross-sectional, N =130; aged 36-60 years) studies. Age-specific intrinsic functional brain network dynamics mediated the link between reproductive aging and perceptions of greater interpersonal adversity. The adolescent profile overlapped areas of greater glutamatergic and dopaminergic receptor density, while the middle-aged profile was concentrated in visual, attentional and default mode networks. The two profiles showed opposite relationships with patterns of functional neural network variability and cortical atrophy observed in psychosis vs major depressive disorder. Our findings underscore the divergent patterns of brain aging linked to reproductive maturation vs senescence, which may explain developmentally specific vulnerability to distinct disorders.