Sex-specific links between stress regulation in early life and anxiety in middle childhood

Psychoneuroendocrinology. 2026 Jun 4;191:107921. doi: 10.1016/j.psyneuen.2026.107921. Online ahead of print.

ABSTRACT

Anxiety disorders become more prevalent in females from middle childhood onwards. Yet it is likely that predictors for developing these disorders occur earlier, with emerging evidence of sex differences. We examined whether early life predictors, including maternal depression, placental cortisol bioavailability, and infant cortisol reactivity, predict sex differences in anxiety disorders at age 8. Data are from 149 mothers recruited in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) before 20 weeks’ gestation and their children followed to 8 years. Maternal measures included the Structured Clinical Interview for DSM-IV, the Edinburgh Postnatal Depression Scale, State-Trait Anxiety Inventory, Childhood Trauma Questionnaire, Parenting Stress Index, and antenatal hair cortisol. At birth, placental 11β-HSD2 mRNA levels were used to inferpotential fetal cortisol exposure. Child measures included salivary cortisol reactivity at 12 months. At age 8, the Diagnostic Interview Schedule for Children and the Child Behavior Checklist were administered. The results show that at age 8, associations were sex-specific: (i) Among females but not males, higher infant 12-month cortisol reactivity and lower placental 11β-HSD2 mRNA were associated with anxiety disorders. (ii) Maternal antenatal antidepressant use was associated with a lower risk of anxiety symptoms in 8-year-old females. (iii) For male children, concurrent maternal depressive symptoms at 8 years were the only significant association with anxiety. In conclusion, our findings identify the possible predictors of sex differences in the early life development for differential susceptibility to later anxiety disorders.

PMID:42258972 | DOI:10.1016/j.psyneuen.2026.107921