Prenatal stress and cortical morphometric similarity network in offspring: Transcriptional signatures of associated genes.

BACKGROUND

Prenatal stress is known to disrupt neurodevelopment in offspring, heightening their risk of mental health disorders. However, its impact on the morphometric similarity network (MSN)-a framework that integrates multiple anatomical features to quantify structural similarity across brain regions in the developing offspring-remains poorly understood.

METHODS

Using data from the Queensland Twin Adolescent Brain (QTAB) longitudinal study focusing on adolescent twins, we investigated the impact of prenatal stress on cortical MSN in 414 early adolescents (aged 9-14 years). Furthermore, we analyzed the relationship between MSN strength alterations associated with prenatal stress and anatomically organized gene expressions. Disease-related analysis and functional enrichment analysis were conducted.

RESULTS

Adolescents exposed to prenatal stress exhibited smaller age-related changes in MSN strength between ages 9 and 14, particularly in regions associated with emotional regulation, cognitive control, and decision-making, despite showing greater similarity at age 9 compared to their unexposed peers. We identified cortical patterns characterized by weighted gene expression, strongly associated with group differences in MSN strength. Gene expressions linked to prenatal stress-related MSN strength changes were correlated with differential gene expression (DGE) implicated in conditions such as autism spectrum disorder (ASD) and inflammatory bowel disease (IBD).

CONCLUSIONS

These results enhance insights into the interplay between gene expression and structural brain changes driven by prenatal stress, highlighting a potential mechanistic link between prenatal stress and neurodevelopmental vulnerability, shedding light on the biological pathways underpinning neurodevelopmental risk factors.