Prenatal Programming of Mental Illness: Current Understanding of Relationship and Mechanisms

Abstract

The British epidemiologist Dr. David J. Barker documented the relationship between infant birth weight and later onset of hypertension, coronary heart disease, insulin resistance, and type II diabetes. A stressful in utero environment can cause long-term consequences for offspring through prenatal programming. Prenatal programming most commonly occurs through epigenetic mechanisms and can be dependent on the type and timing of exposure as well as the sex of the fetus. In this review, we highlight the most recent evidence that prenatal programming is implicated in the development of psychiatric disorders in offspring exposed to maternal stress during pregnancy. Methodological differences between studies contribute to unavoidable heterogeneity in study findings. Current data suggest that fetal exposure to maternal hypothalamic-pituitary-adrenal axis dysregulation, excessive glucocorticoids, and inflammation with resulting epigenetic changes at both the placental and fetal levels are important areas of continued investigation.

Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle?

“…The negative influence exerted by adverse life events during gestation on brain development has received a great deal of attention since the proposal that psychiatric disorders may be developmental in origin (Barker, 2013, Capra et al, 2013, Kim et al, 2015. Brain development begins early in embryonic life with neurulation, where the neural plate is transformed into the neural tube at approximately two to three weeks gestation Barone, 2000, Workman et al, 2013).…”

Hormone levels in neonatal hair reflect prior maternal stress exposure during pregnancy

“…First, it is often informative to assess cortisone in addition to cortisol when assessing hair (Ito et al, 2005; Keckeis et al, 2012). Second, a comprehensive panel is especially important when investigating prenatal stress, because it is known that other hormones synthesized by the adrenal and gonads can be affected (DiPietro et al, 2011; Kapoor and Matthews, 2008, 2011; Kim et al, 2015; Pepe and Albrecht, 1995; Sharp et al, 2014). For example, prenatal stress in some animal species has been shown to affect sexual differentiation by influencing the organizational actions of androgens and estrogens.…”

The neuroscience and context of adolescent depression

“…Importantly, stress-related pathology can be trans-generationally transmitted through epigenetic phenomena and changes in gene expression have been shown to persist long after the initial stress exposure, which may predispose the individual for disease in later life (41). The effects of high maternal stress levels during pregnancy appear to be transmitted to one or two subsequent generations, which may result in an accumulative increase in vulnerability to depression in future generations (42).…”