Maternal Prenatal Depression in Pregnancies With Female and Male Fetuses and Developmental Associations With C-reactive Protein and Cortisol

• Published in: Biological psychiatry : cognitive neuroscience and neuroimaging 2021-03, Vol.6 (3), p.310-320
• Main Authors: Freedman, Robert, Hunter, Sharon K., Noonan, Kathleen, Wyrwa, Anna, Christians, Uwe, Law, Amanda J., Hoffman, M. Camille
• Format: Article
• Language: English
• Subjects: C-Reactive Protein; Child; Depression; Female; Fetus; Humans; Hydrocortisone; Hydroxycortisone; Hypothalamo-Hypophyseal System; Infant, Newborn; Inflammation; Male; Pituitary-Adrenal System; Pregnancy; Prenatal Exposure Delayed Effects; Stress, Psychological
• ISSN: 2451-9022; 2451-9030
• DOI: 10.1016/j.bpsc.2020.08.003

Prenatal depression has lasting effects on development in offspring, including later mental illness risk. Maternal responses to depression include inflammation and hypothalamic-pituitary-adrenal axis stimulation. Effects on development of cerebral inhibitory neurocircuits may differ for female and male fetuses. Mothers (N = 181) were assessed periodically, beginning at 16 weeks’ gestation, using the Center for Epidemiologic Studies–Depression Scale. Maternal prenatal C-reactive protein and hair cortisol and cortisone levels were determined. Cortisone was determined in neonatal hair. Development of cerebral inhibitory neurocircuits was assessed in 162 1-month-old newborns by inhibition of P50 electrophysiological responses to repeated sounds. Maternal depression was associated with decreased newborn P50 inhibition in both sexes. Maternal C-reactive protein levels were significantly associated with depression only in pregnancies with male fetuses and with decreased newborn P50 inhibition only in male newborns. Maternal cortisol levels were significantly associated with depression only in pregnancies with female fetuses and with decreased newborn P50 inhibition only in female newborns. In pregnancies with male fetuses compared with pregnancies with female fetuses, cortisol was more robustly metabolized to cortisone, which does not activate cortisol receptors. This study finds sex-specific associations of C-reactive protein and cortisol levels with prenatal depression in women and with decreased development of newborn P50 inhibition. Sex-based differences in maternal response to depression with inflammation or cortisol and their developmental effects may reflect evolutionary influences to promote survival in adversity. Decreased newborn P50 inhibition is associated with later childhood behavioral problems, and decreased P50 inhibition is a pathophysiological feature of several mental illnesses.