Placental programming of neuropsychiatric disease

Abstract

The placenta is vital for fetal growth, and compromised function is associated with abnormal development, especially of the brain. Linking placental function to brain development is a new field we have dubbed neuroplacentology. Approximately 380,000 infants in the United States each year abruptly lose placental support upon premature birth, and more than 10% of pregnancies are affected by more insidious placental dysfunction such as preeclampsia or infection. Abnormal fetal brain development or injury can lead to life-long neurological impairments, including psychiatric disorders. The majority of research connecting placental compromise to fetal brain injury has focused on gas exchange or nutritional programming, neglecting the placenta's essential neuroendocrine role. We will review the current evidence that placental dysfunction, particularly endocrine dysfunction, secretion of pro-inflammatory cytokines, or barrier breakdown may place many thousands of fetuses at risk for life-long neurodevelopmental impairments each year. Understanding how specific placental factors shape brain development and increase the risk for later psychiatric disorders, including autism, attention deficit disorder, and schizophrenia, paves the way for novel treatment strategies to maintain the normal developmental milieu and protect from further injury.

Figure 1

Critical periods of development and corresponding symptomatology of neuropsychiatric disorders.