Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

Abstract

Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.

Keywords: S-adenosylmethionine; epigenetics; major depressive disorder; malnutrition; micronutrients; mineral deficiency; omega 3 polyunsaturated fatty acids; pre/probiotics.

Figure 1

Compiled evidence related to epigenetic changes involved in major depressive disorder (MDD). As shown, chronic stress, early-life stress, and prenatal stress accompanied with nutrient restriction are pivotal drivers of the epigenetic modifications observed in patients with MDD. These changes include histone modifications, altered DNA methylation patterns, and the dysregulation of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNA (lnRNA). Some of the most relevant findings collected in this manuscript for each modification are summarized. These variations lead to important alterations in the brain synapsis, anhedonia, social defeat stress, neurodevelopment, brain plasticity and function, and many other depressive symptoms.

Figure 2

The link between diet, epigenetics, and MDDs. As summarized, a set of nutrients, foods, and dietary strategies are able to influence different epigenetic mechanisms like DNA methylation, histone modifications, non-coding RNAs, and gut microbiota-immune system composition and their products thereby influencing in the pathophysiology of MDD.