Prenatal SSRI exposure alters neonatal corticosteroid binding globulin, infant cortisol levels, and emerging HPA function

Psychoneuroendocrinology. 2012 Jul;37(7):1019-28. doi: 10.1016/j.psyneuen.2011.11.011. Epub 2011 Dec 15.

Abstract

Background: Serotonin influences the development of the hypothalamic-pituitary-adrenal (HPA) system; therefore prenatal exposure to selective serotonin reuptake inhibitor antidepressants (SSRIs) may alter HPA axis development and function. To address this, prenatal exposure to SSRIs and maternal mood were examined in relation to neonatal and infant levels of cortisol and its binding protein, corticosteroid-binding globulin (CBG).

Methods: Serum cortisol and CBG levels were assayed from SSRI-exposed and non-exposed mothers and their neonates at delivery. Maternal mood symptoms were documented at 36 weeks gestation. To determine the long-term implications of changes in CBG, levels of salivary cortisol were assessed in infants at 3 months of age.

Results: Prenatal SSRI exposure significantly increased serum CBG levels in neonates after vaginal delivery (p ≤ 0.038), even when controlling for maternal depression. Neonatal serum cortisol levels did not vary with SSRI exposure or antenatal maternal mood, but were significantly higher following vaginal delivery (p ≤ 0.003). Neonatal serum CBG levels were associated with infant salivary levels of evening cortisol (p ≤ 0.051). In SSRI-exposed infants, increased levels of neonatal CBG predicted a smaller diurnal change in infant salivary cortisol (p ≤ 0.028), regardless of maternal depression.

Conclusions: Prenatal SSRI exposure affects the developing HPA system by altering serum CBG levels in neonates and infant salivary cortisol levels. Further research is warranted on the long-term functional implications of the effect of prenatal SSRI exposure on fetal hepatic CBG gene expression and the developing HPA system.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / growth & development
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiology
  • Infant
  • Infant, Newborn / blood
  • Infant, Newborn / metabolism*
  • Male
  • Maternal Exposure / statistics & numerical data
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / growth & development
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiology
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Prenatal Exposure Delayed Effects* / blood
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / metabolism
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Saliva / drug effects
  • Saliva / metabolism
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Transcortin / metabolism*

Substances

  • Antidepressive Agents
  • SERPINA6 protein, human
  • Serotonin Uptake Inhibitors
  • Transcortin
  • Hydrocortisone