New research highlights how functional brain variability mediates the relationship between reproductive aging and psychological vulnerability in females, offering insights into why early puberty and premature menopause correlate with mental health risks.

In a study published in Nature Mental Health, researchers analyzed brain imaging data from 571 females across 2 age groups: adolescents (9 to 12) and middle-aged women (36 to 60). Using partial least squares (PLS) analysis, they identified functional connectivity variability (FCV) as a mediator between accelerated reproductive aging and perceptions of social adversity.

"Our findings underscore the divergent patterns of brain aging linked to reproductive maturation versus senescence, which may explain developmentally specific vulnerabilities to distinct disorders,” wrote lead author Raluca Petrican, PhD, University of Liverpool.

The study observed that earlier pubertal timing in adolescents and accelerated menopause in middle-aged women correlated with greater FCV. In adolescents, these changes were linked to brain regions dense in glutamatergic and dopaminergic receptors, suggesting heightened psychosis risk. For middle-aged women, FCV changes in visual, attentional, and default mode networks aligned with increased vulnerability to depression.

Neuroimaging data came from the Adolescent Brain and Cognitive Development (ABCD) study and Human Connectome Project-Aging (HCP-A). Results also implicated serotonin and dopamine pathways in mediating interpersonal adversity but not pain sensitivity.

The authors emphasize the study’s cross-sectional design limits causal interpretations, and longitudinal research is necessary. Nevertheless, the findings underscore how accelerated reproductive aging intersects with brain variability, providing potential targets for age-appropriate interventions.

The authors declared no competing interests.