Cortical Thinning and Neuropsychiatric Outcomes in Children Exposed to Prenatal Adversity: A Role for Placental CRH?

Am J Psychiatry. 2018 May 1;175(5):471-479. doi: 10.1176/appi.ajp.2017.16121433. Epub 2018 Mar 2.


Objective: The authors sought to assess associations among early-life exposure to adversity, the development and maturation of neurons and brain circuits, and neurodevelopmental outcomes. Specifically, they examined whether fetal exposure to placental corticotropin-releasing hormone (CRH), a molecule conveying maternal signals to the fetus, predicts brain growth and neuropsychiatric outcomes in school-age children.

Method: In a large, well-characterized prospective cohort, concentrations of placental CRH (pCRH) in maternal plasma were determined during five intervals during gestation. When the children reached school age, their brain structures were examined using MRI, and emotional and cognitive tests assessing internalizing and externalizing behaviors and attention were administered (N=97, 49 of them girls).

Results: Levels of pCRH during gestation predicted structural and functional brain outcomes in children. Specifically, fetal exposure to elevated pCRH levels was associated with thinning of selective cortical regions and with commensurate cognitive and emotional deficits. The relations among fetal exposure to pCRH, cortical thinning, and childhood function were sex specific.

Conclusions: In view of the established effects of CRH on maturation and arborization of cortical neurons, and the major contribution of dendrites to cortical volume, these findings position pCRH as an important mediator of the consequences of early-life adversity on neuropsychiatric outcomes.

Keywords: Biological Markers; Child Psychiatry; Cognitive Neuroscience; Magnetic Resonance Imaging; Stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adverse Childhood Experiences*
  • Affective Symptoms / physiopathology*
  • California
  • Cerebral Cortex / abnormalities*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / growth & development
  • Child
  • Cognition Disorders / physiopathology*
  • Corticotropin-Releasing Hormone / physiology*
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Placenta / physiopathology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / diagnostic imaging
  • Risk Factors
  • Sex Factors


  • Corticotropin-Releasing Hormone