Fetal programming of neuropsychiatric disorders

Abstract

Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life. Birth Defects Research (Part C) 108:207-223, 2016. © 2016 Wiley Periodicals, Inc.

Choline, Other Methyl-Donors and Epigenetics

“…Timing of nutrient availability is important in determining epigenetic outcomes; changes in availability during early life potentially having a greater effect than changes occurring later in life. The Developmental Origins of Health and Disease (DOHaD) hypothesis [95] is that diet in early life influences developmental plasticity and alters susceptibility to adult cardiovascular disease, type 2 diabetes, obesity [96], neuropsychiatric diseases [97], immune/inflammatory diseases [98] and cancer [99]. Epigenetic mechanisms are likely a major mechanism of DOHaD [100].…”

Identifying epigenetic targets underlying the effects of prenatal exposure to opioids

“…Epigenetic modifications have been identified as one molecular mechanism that may contribute to the lasting neurodevelopmental effects observed in children exposed to opioids in utero. 3 The OPRM1 gene codes for the μ opioid receptor and is a strong candidate for sensitivity to opioids. Many human genetic studies have found associations between this gene and opioid-use disorders, and animal research supports the role of this gene, using a variety of drugrelated behavioral models.…”

Shining a light on early stress responses and late-onset disease vulnerability

“…There is increasing evidence that neurodegenerative and neuropsychiatric disorders have developmental components to pathogenesis that encompass a prodromal phase associated with regional impairments in neural cell maturation and maintenance, neural network connectivity, and oscillatory synchrony (1,2). These abnormal developmental states elicit a spectrum of homeostatic mechanisms and predispose to late-onset disease.…”