Article summary of Placental programming of neuropsychiatric disorders by Kratimenos & Penn - Chapter

What is neuroplacentology?

Neuroplacentology is the field that investigates placental connections to neurodevelopmental outcomes. Many evens can abruptly change the fetal´s brain environment. The developmental potential of the fetus can be compromised when the placenta fails to function properly. Placental failure can directly damage the developing brain or increase its susceptibility to injury, leading to permanent neurological disabilities.

What is fetal programming?

Fetal programming suggests that certain events occurring during critical points of pregnancy may cause permanent effects on the fetus and infant long after birth. Maternal health, nutrition, exposure to environmental factors, uteroplacental blood flow, placental transfer, and fetal genetic and epigenetic responses all contribute to programming.

How can placental events influence brain development?

At certain point the embryo and fetus are more vulnerable to stressful events and the impact of those events will vary depending on when they occur during gestation. Several placental events are distinguished:

• Preterm birth has big impacts on postnatal neurodevelopment and additional complications, such as infection, may cause bigger issues as well. Events before preterm birth, such as IUGR due to impaired placental function, may also enhance the risk of neurodevelopmental impairment in premature infants.
• Maternal infection has been implicated in the etiology of neuropsychiatric disorders, including ASD, generalized cognitive impairment, and schizophrenia. Direct infection of the placenta is associated with adverse outcomes in the embryo and fetus.
• The placental genetic program shows an abrupt shift in overall gene expression pattern in midgestation. Many genes that are highly expressed in placenta are also expressed in brain diseases.
• Hypermethylation and hypomethylation are placental factors that can cause neuropsychiatric disease.
• Placental dysfunction, or when the placenta is not protecting the developing fetus from maternal insults, can lead to inflammation, hypercoagulable placental state, or altered glucocorticoid levels. This may lead to fetal tissues being exposed to higher than normal glucocorticoid levels, suppressing cell proliferation, and inducing epigenetic changes.
• Maternal stressors, such as hypoxia or malnutrition, may directly impact the developing fetus or alter gene expression. The effect of maternal stress on the placenta may be amplified by the presence of comorbidities.

What is the role of the placenta in autism?

Research suggests a correlation between placental architecture and later ASD. Studies examining the placenta of mothers who were at higher risk of having a child with autism revealed anatomical variations, such as fewer branch points, thicker and less tortuous arteries, better extension to the surface boundary, smaller branch angles, and thicker and rounder placentas. The correlations suggest that placentas may reflect or create an adverse environment for fetal brain development. Other studies suggest a link between placental epigenetic modification to ASD, for example through pesticide exposures that alter placental DNA methylation and vitamin D deficiency.

What is the role of the placenta in schizophrenia?

Research suggests an association between maternal viral illnesses in early gestation with later development of schizophrenia in the child. Maternal infection may permanently affect the placenta and fetus either through altered gene expression or epigenetic modification. There is also a genetic risk for schizophrenia. A subset of the most significant genetic variants associated with schizophrenia, combined with the ability of the brain cells to respond to stress, may determine the final phenotype.

What is the role of the placenta in mood disorders?

The developing brain is very sensitive to glucocorticoids which play an important role in neuronal maturation. Many maternal stressors, such as depression, trauma, and malnutrition, can alter maternal glucocorticoid levels and affect the placenta. Also, poor placental function that is associated with IUGR can alter fetal glucocorticoid exposure. Maternal mood disorders are associated with disruption of placental enzymes that regulate maternal-fetal glucocorticoid and serotonin transfer. This may lead to abnormal neurodevelopment and potentially to mood disorders in the child.

What is the role of the placenta in disorders of executive functioning?

Research shows that learning difficulties and behavioral problems are significantly associated with deficits in executive functioning and are thought to be caused by prefrontal lobe dysfunction. Especially premature neonates show executive function deficits in childhood or adult life. There are differences between late premature neonates that were medically and purposely delivered versus those that were spontaneously born. Those who were delivered for medical indications had higher levels of childhood attention problems. It suggests that pregnancy complications that motivated medical intervention, complications that are primarily due to placental dysfunction and fetal growth restriction, can increase the risk of executive functioning deficits.