Sex-specific influences of prenatal inflammation on offspring psychological symptoms in late midlife.

INTRODUCTION

Prenatal maternal inflammation (PNMI) is associated with offspring psychopathology with evidence for sex-specific effects. The current study examined psychological symptoms in offspring during late midlife following exposure to PNMI and explored differential effects of timing of exposure and offspring sex.

METHODS

Mother-offspring dyads (N = 139) were ascertained from the Child Health and Development Studies (CHDS) cohort. Data were available for Interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA), and soluble tumor necrosis factor receptor-II (sTNF-RII) from archived trimester 1 (T1) and trimester 2 (T2) maternal prenatal sera. Offspring in late midlife (57-62 years) reported depressive (CES-D) and anxiety (STAI-A, trait form) symptoms, frequency of psychotic-like experiences (PLE; CAPE-P15), and were interview assessed for substance use disorder (SUD; SCID-5).

RESULTS

Higher levels of T1 PNMI were related to greater frequency of PLE (IL-6, p < 0.01), less depressive symptoms (sTNF-RII), and greater odds of SUD (IL-1RA) (both p < 0.05). Offspring sex moderated an association between higher T1 PNMI and greater anxiety symptoms (IL-6), such that associations were stronger for male offspring. (p < 0.05). In contrast, offspring sex moderated an association between higher T2 PNMI and greater depressive (IL-6, IL-8) and anxiety symptoms (IL-6, IL-1RA), such that associations were stronger for female offspring (IL-6 p < 0.001; others p < 0.05).

CONCLUSIONS

These findings show timing- and sex-specific relationships between PNMI and offspring psychological symptom domains in late midlife and further clarify the impact of PNMI on psychopathology at later stages of life.