Fetal Nutrition Interactions with Complex Traits of Mental Disorders

Complex traits do not follow traditional Mendelian inheritance rules. Instead they depend on multiple genes and can also be influenced by environmental factors (Wright, 1931; Gillham, 2011). Schizophrenia does not mendelize because it has many associated genes; there are several environmental determinants; and there are interactions between genes and the environment that contribute to disease pathology. Schizophrenia also varies along several continua, including age of onset and severity. Some patients remain highly functional while others are incapacitated (Kandel, 2018, p. 89). Thus, schizophrenia is characterized as a complex trait.

A 2014 genome wide association scan (GWAS) identified 108 genetic loci (locations in the genome) associated with schizophrenia, indicating multiple genes are involved in the disease pathology (Ripke et al., 2014). There are also several studies linking prenatal famine, an environmental factor, to schizophrenia. Two studies on the Dutch famine of 1944-45 found that risk of schizophrenia peaked for those exposed in the first trimester to prenatal famine (Susser & St. Clair, 2013), which refers to the placental environment of a fetus whose mother experiences undernutrition. Two large studies of the Chinese famine of 1959-1961 yielded similar results (Susser & St. Clair, 2013). Ursini et al., 2018 found evidence of the interaction between genetic risk factors and environment through analysis of polygenic risk scores; i.e., scores that predict a trait based on an individual’s genetic variants at multiple associated loci, which are weighted based on the strength of association to the trait. The authors found that many variants strongly associated with schizophrenia are more common in patients with early-life complications (ELC’s), potentially harmful events in pregnancy or during labor. They also found that these same loci are upregulated in pregnancies with complications. This indicates a two-way interaction between genes and environment.

Moreover, current health practices and public health initiatives should have a greater and more holistic focus on fetal nutrition to reduce morbidity of mental disorders in adulthood. In addition to the aforementioned studies of the Dutch and Chinese famines linking prenatal famine with increased risk of schizophrenia (Susser & St. Clair, 2013), another study linked inadequate gestational weight gain in a well-fed population with nonaffective psychosis, the umbrella term for psychiatric disorders that do not affect mood, including schizophrenia (Susser & Keyes, 2017). Together, these studies provide substantial support for the importance of fetal nutrition on mental health later in life. While substantial information about the influence of prenatal micronutrients exists, they are usually studied in isolation. Conversely, they often act in sets, with the intake of one impacting the effectiveness of others (Susser & Keyes, 2017). Instead of focusing narrowly on one or a few micronutrients, health practices should involve a holistic approach to boosting fetal nutrition during pregnancy.

Acknowledgments

I thank Prof. Maryellen Ruvolo, my professor for HEB 1600 at Harvard, for her feedback on an early version of this article.

References

Gillham, N. W. (2011). Genes, Chromosomes, and Disease: From Simple Traits, to Complex Traits, to Personalized Medicine. Upper Saddle River, NJ: Pearson Education, Inc.

Kandel, E. R. (2018). The disordered mind: What unusual brains tell us about ourselves (p. 89). New York, NY: Farrar, Straus and Giroux.

Ripke, S., Neale, B. M., Corvin, A., Walters, J. T., Farh, K. H., Holmans, P. A., ... & Pers, T. H. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421.

Susser, E. & Keyes, K. M. (2017). Prenatal Nutritional Deficiency and Psychosis: Where Do We Go From Here? JAMA psychiatry, 74(4), 349-350.

Susser, E. & St Clair, D. (2013). Prenatal famine and adult mental illness: interpreting concordant and discordant results from the Dutch and Chinese Famines. Social science & medicine (1982), 97, 325.

Ursini, G., Punzi, G., Chen, Q., Marenco, S., Robinson, J. F., Porcelli, A., ... & Seidel, J. (2018). Convergence of placenta biology and genetic risk for schizophrenia. Nature medicine, 24(6), 792.

Wright, S. (1931). Evolution in Mendelian Populations. Genetics, 16(2), 97-159.

Photo Credits (in order of appearance)

1. Sbtlneet/Pixabay, 2. StockSnap/Pixabay, 3. Free-Photos/Pixabay.

Tags

#ComplexTraits #PsychiatricDisorder #Schizophrenia # NonaffectivePsychosis #HumanGenome #Genetics #GWAS #PrenatalHealth #HumanFetus #Famine #Hunger #Neuroscience