Neurological and Epigenetic Implications of Nutritional Deficiencies on Psychopathology: Conceptualization and Review of Evidence

Abstract

In recent years, a role for epigenetic modifications in the pathophysiology of disease has received significant attention. Many studies are now beginning to explore the gene–environment interactions, which may mediate early-life exposure to risk factors, such as nutritional deficiencies and later development of behavioral problems in children and adults. In this paper, we review the current literature on the role of epigenetics in the development of psychopathology, with a specific focus on the potential for epigenetic modifications to link nutrition and brain development. We propose a conceptual framework whereby epigenetic modifications (e.g., DNA methylation) mediate the link between micro- and macro-nutrient deficiency early in life and brain dysfunction (e.g., structural aberration, neurotransmitter perturbation), which has been linked to development of behavior problems later on in life.

A ‘phenotypic hangover’: the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome of Drosophila melanogaster

“…Further, nutrient availability during the pre and postnatal periods can lead to long-lasting changes in neuron development [ 100 ] as well as influence the development of psychopathological behaviour [ 101 ]. This is because nutritional deficit may lead to altered brain development [ 102 ], possibly via epigenetic factors that can lead to changes in brain structure and function [ 103 ]. Micronutrient availability can heavily influence neurotransmission, due to the fact that the function of the brain is inherently related to its metabolism of nutrients [ 103 ] in the form of vitamins and minerals that function as co-enzymes in neurotransmission and neurotransmitter metabolism.…”

A ‘phenotypic hangover’ – the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome ofDrosophila melanogaster

“…Further, nutrient availability during the pre and postnatal periods can lead to long-lasting changes in neuron development (Niculescu et al, 2004), as well as influence the development of psychopathological behaviour (Neugebauer et al, 1999). This is because nutritional deficit may lead to altered brain development (Liu and Raine, 2006), possibly via epigenetic factors that can lead to changes in brain structure and function (Liu et al, 2015). Given that micronutrient availability can heavily influence neurotransmission, due to the fact that the function of the brain is inherently related to its metabolism of nutrients (Liu et al, 2015) in the form of vitamins and minerals that function as co-enzymes in neurotransmission and neurotransmitter metabolism, our gene expression data are supportive of these linkages.…”

“…Nutritional deficiency may also lead to the development of psychopathological behaviour such as antisocial, violent and criminal behaviour (Neugebauer et al, 1999). This may in part be a consequence of the capacity of nutritional deficiency to alter brain development (Liu and Raine, 2006), possibly through epigenetic factors, which may lead to changes in brain structure and function (Liu et al, 2015). Supporting this is the suggestion that macronutrient deficiency can cause changes in epigenetic regulation, which can lead to impaired brain development, signalling molecule imbalance, neurotoxicity and differences in neurotransmission (Liu et al, 2015) which all contribute to psychopathological outcomes.…”

“…This may in part be a consequence of the capacity of nutritional deficiency to alter brain development (Liu and Raine, 2006), possibly through epigenetic factors, which may lead to changes in brain structure and function (Liu et al, 2015). Supporting this is the suggestion that macronutrient deficiency can cause changes in epigenetic regulation, which can lead to impaired brain development, signalling molecule imbalance, neurotoxicity and differences in neurotransmission (Liu et al, 2015) which all contribute to psychopathological outcomes. For example, studies into participants from the Dutch Hunger Winter cohort found correlations between prenatal famine exposure and schizophrenia (Susser and Lin, 1992, Susser et al, 1996), along with persistent epigenetic changes at, e.g.…”

Maternal obesity reprograms offspring's executive brain centers in a sex‐specific manner?

“…Evidence from animal studies confirms that maternal over‐nutrition or high‐fat diet (HFD) feeding lowers circulating folate and micronutrient levels in offspring, leading to global alterations in DNA methylation status in the brain (Liu et al . ; Sullivan et al . ).…”