Abstract
The effects on child health and development of exposure to either general malnutrition or to specific micronutrient deficiencies during early life are well documented (Annals of the New York Academy of Sciences 1136:172–184, 2008). For example, prenatal folate deficiency increases the risk of neural tube defects, and low maternal iodine intake can cause fetal iodine deficiency syndrome and cretinism (Lancet 338(8760):131–137, 1991; Lancet 1(7694):308–310, 1971; Journal of Nutrition 130:493S–495S, 2000; Nutrients 3:265–273, 2011). However, the impact of malnutrition during early life is not restricted to infancy and childhood. It is now clear that there are latent effects that may only become evident in adult life. The prenatal antecedents responsible for these latent effects can arise from exposures at any point from conception onward (Mothers, babies and health in later life. Edinburgh, Scotland: Churchill Livingstone, 1998; Schizophrenia Bulletin 34(6):1054–1063, 2008).
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References
Delisle HF. Poverty: the double burden of malnutrition in mothers and the intergenerational impact. Ann NY Acad Sci. 2008;1136:172–84.
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338(8760):131–7.
Pharoah PO, Buttfield IH, Hetzel BS. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet. 1971;1(7694):308–10.
Hetzel BS. Iodine and neuropsychological development. J Nutr. 2000;130:493S–5S.
Skeaff S, Iodine A. Deficiency in pregnancy: the effect on neurodevelopment in the child. Nutrients. 2011;3:265–73.
Barker DJ. Mothers, babies and health in later life. Edinburgh: Churchill Livingstone; 1998.
Brown AS, Susser ES. Prenatal nutritional deficiency and risk of adult schizophrenia. Schizophr Bull. 2008;34(6):1054–63.
Stein ZA, Susser M, Saenger G, et al. Famine and human development: the Dutch hunger winter of 1944–1945. New York: Oxford University Press; 1975.
Lumey LH. Decreased birthweights in infants after maternal in uteroexposure to the Dutch famine of 1944–1945. Paediatr Perinat Epidemiol. 1992;6(2):240–53.
Kuh D, Ben-Shlomo Y. A life course approach to chronic disease epidemiology. New York: Oxford University Press; 2004.
Huang JS, Lee TA, Lu MC. Prenatal programming of childhood overweight and obesity. Matern Child Health J. 2007;11(5):461–73.
Kyle UG, Pichard C. The Dutch Famine of 1944–1945: a pathophysiological model of long-term consequences of wasting disease. Curr Opin Clin Nutr Metab Care. 2006;9(4):388–94.
Painter RC, Roseboom TJ, Bleker OP. Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol. 2005;20(3):345–52.
Lumey LH, Stein AD, Susser E. Prenatal famine and adult health. Annu Rev Public Health. 2011;32:237–62.
An overstretched hypothesis. Lancet. 2011;357:405.
Susser E, Hoek HW, Brown A. Neurodevelopmental disorders after prenatal famine: the story of the Dutch Famine Study. Am J Epidemiol. 1998;147(3):213–6.
Susser E, Neugebauer R, Hoek HW, et al. Schizophrenia after prenatal famine. Further evidence. Arch Gen Psychiatry. 1996;53(1):25–31.
Hulshoff Pol HE, Hoek HW, Susser E, et al. Prenatal exposure to famine and brain morphology in schizophrenia. Am J Psychiatry. 2000;157(7):1170–2.
Hoek HW, Brown AS, Susser E. The Dutch famine and schizophrenia spectrum disorders. Soc Psychiatry Psychiatr Epidemiol. 1998;33(8):373–9.
Franzek E, Sprangers N, Janssens ACJW, et al. Prenatal exposure to the 1944–5 Dutch “hunger winter” and addiction later in life. Addiction. 2008;103:433–8.
Neugebauer R, Hoek HW, Susser E. Prenatal exposure to wartime famine and development of antisocial personality disorder in early adulthood. JAMA. 1999;282(5):455–62.
Brown A, Susser ES, Lin SP, et al. Increased risk of affective disorders in males after second trimester prenatal exposure to the Dutch Hunger Winter of 1944–55. Br J Psychiatry. 1995;166:601–6.
Brown A, van Os J, Driessens C, et al. Further evidence of relation between prenatal famine and major affective disorder. Am J Psychiatry. 2000;157:190–5.
Stein AD, Pierik FH, Verrips GHW, et al. Maternal exposure to the Dutch Famine before conception and during pregnancy: quality of life and depressive symptoms in adult offspring. Epidemiology. 2009;20:909–15.
Stein Z, Susser M, Saenger G, et al. Nutrition and mental performance. Science. 1972;178(62):708–13.
De Groot RH, Stein AD, et al. Prenatal famine and IQ aged 59. Int J Epidemiol. 2011;40:327–37.
St. Clair D, Xu M, Wang P, et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA. 2005;294(5):557–62.
Xu MQ, Sun WS, Liu BX, et al. Prenatal malnutrition and adult schizophrenia: further evidence from the 1959–61 Chinese famine. Schizophr Bull. 2009;35(3):568–76.
Susser E, St. Clair D. Prenatal famine and adult mental illness; interpreting concordant and discordant results from Dutch and Chinese famines. Soc Sci Med. 2013;97:325–30.
World Health Organization. The World Health Report 2001: mental health: new understanding, new hope. Geneva: World Health Organization; 2001.
Fusar-Poli P, Borgwardt S, Bechdolf A, et al. The Psychosis high risk state: a comprehensive state of the art review. JAMA. 2013;70:107–20.
Pasamanick B, Rogers ME, Lilienfeld AM. Pregnancy experience and the development of behavior disorders in children. Am J Psychiatry. 1956;112(8):613–8.
Hoek HW, Susser E, Buck KA, et al. Schizoid personality disorder after prenatal exposure to famine. Am J Psychiatry. 1996;153(12):1637–9.
Owen MJ, Craddock N, Jablensky A. The genetic deconstruction of psychosis. Schizophr Bull. 2007;33(4):905–11.
St. Clair D. Structural and copy number variants in the human genome: implications for psychiatry. Br J Psychiatry. 2013;202:5–6.
Neugebauer R. Accumulating evidence for prenatal nutritional origins of mental disorders. JAMA. 2005;294(5):621–3.
Picker JD, Coyle JT. Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia? Harv Rev Psychiatry. 2005;13(4):197–205.
McClellan JM, Susser E, King MC. Maternal famine, de novo mutations, and schizophrenia. JAMA. 2006;296(5):582–4.
Gluckman PD, Hanson AM, Cooper C. The effect of in utero and early life conditions on adult health and disease. N Engl J Med. 2008;359:61–73.
Seckl J. Glucocorticoid programming of the fetus; adult phenotypes and molecular mechanisms. Mol Cell Endocrinol. 2001;185:61–71.
Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part one: outcomes. Nat Rev Endocrinol. 2014;10:391–402.
Mosiadis VG, Matthews SG. Glucocorticoids and fetal programming part one: mechanisms. Nat Rev Endocrinol. 2014;10:403–11.
Khashan A, Abel KM, McNamee R, et al. Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Arch Gen Psychiatry. 2008;65(2):146–52.
Abel K, Heuvelman HP, Jorgensen L, et al. Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: a population based cohort study. Br Med J. 2014;348:f7679.
Kong A. Rate of de novo mutations and importance of fathers age to disease risk. Nature. 2012;488:471–5.
Malaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry. 2001;58(4):361–7.
Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003;23(15):5293–300.
Drake AJ, Walker BR, et al. The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol. 2004;180:1–16.
Zhang S, Rattanatray L, MacLaughlin SM, et al. Periconceptual under nutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring. FASEB J. 2010;24:2772–82.
Radford E, Ito M, Shi H, et al. In utero undernourishment perturbs adult sperm methylome and intergenerational metabolism. Science. 2014;345:786–93.
Petronis A. The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis. Biol Psychiatry. 2004;55(10):965–70.
Kirkbride JB, Susser E, Kundakovic M, et al. Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects. Epigenomics. 2012;2012(4):303–15.
Perrin M, Brown AS, Malaspina D. Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia. Schizophr Bull. 2007;33(6):1270–3.
Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008;105(44):17046–9.
Tobi EW, Goeman JJ, Monajemi R. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun. 2014;5:5592.
Wahlberg K, Wynne LC, Oja H, et al. Gene–environment interaction in vulnerability to schizophrenia: findings from the Finnish adoptive family study of schizophrenia. Am J Psychiatry. 1997;154:355–62.
McGrath J, Brown A, St. Clair D. Prevention of schizophrenia—role of dietary factors. Schizophr Bull. 2011;37:272–83.
Insel B, Schaefer CA, McKeague IW, Susser ES, Brown AS. Maternal iron deficiency and the risk of schizophrenia in offspring. Arch Gen Psychiatry. 2008;65(10):1136–44.
Brown J, Foster HD. Schizophrenia: an update of the selenium deficiency hypothesis. J Orthomol Med. 1996;11(4):211–22.
Foster H. The geography of schizophrenia: possible links with selenium and calcium deficiencies, inadequate exposure to sunlight and industrialization. J Orthomol Med. 1988;3(3):135–40.
Brown J. Role of selenium and other trace elements in the geography of schizophrenia. Schizophr Bull. 1994;20(2):387–98.
Vidovic B, Dorđević B, Milovanović S, et al. Selenium zinc and plasma copper levels in patients with schizophrenia relationship to metabolic risk factors. Biol Trace Elem Res. 2013;1–3:22–8.
Behne D, Hilmert H, Scheid S. Evidence for specific selenium target tissues and new biologically important selenoproteins. Biochim Biophys Acta. 1988;966(1):12–21.
Castaño A, Cano J, Machado A. Low selenium diet affects monamine turnover differentially in substantia nigra and striatum. J Neurochem. 1993;61(4):1302–7.
Benton D. Selenium intake, mood, and other aspects of psychological functioning. Nutr Neurosci. 2002;5(6):363–74.
Schweizer U, Schomburg L. Selenium, selenoproteins and brain function. In: Hatfield D, Berry MJ, Gladyshev VN, editors. Selenium: its molecular biology and role. New York: Springer; 2006.
Yan J, Barrett JN. Purification from bovine serum of a survival-promoting factor for cultured neurons and its identification as Selenoprotein-P. J Neurosci. 1998;18(21):8682–91.
Savaskan N, Bräuer AJ, Kühbacher M, et al. Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity. FASEB J. 2003;17(1):112–4.
Mitchell J, Nicol F, Beckett GJ, Arthur JR. Selenoprotein expression and brain development in preweanling selenium- and iodine-deficient rats. J Mol Endocrinol. 1998;20:203–10.
Xiang N, Zhao R, Song G, Zhong W. Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells. Carcinogenesis. 2008;29(11):2175–81.
Davis C, Uthus EO, Finley JW. Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon. J Nutr. 2000;130:2903–9.
Uthus E, Ross SA. Dietary selenium affects homocysteine metabolism differently in Fisher-344 rats and CD-1 mice. J Nutr. 2007;137:1132–6.
Hu Y, Diamond AM. Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res. 2003;63:3347–51.
Lei C, Niu X, Wei J, Zhu J, et al. Interaction of glutathione peroxidase-1 and selenium in endemic dilated cardiomyopathy. Clin Chim Acta. 2009;399(1–2):102–8.
Andrews R. Unification of the findings in schizophrenia by reference to the effects of gestational zinc deficiency. Med Hypotheses. 1990;31:141–53.
Andrews R. An update of the zinc deficiency theory of schizophrenia. Identification of the sex determining system as the site of action of reproductive zinc deficiency. Med Hypotheses. 1992;38:284–91.
Merialdi M, Caulfield LE, Zavaleta N, et al. Adding zinc to prenatal iron and folate tablets improves fetal neurobehavioral development. Am J Obstet Gynecol. 1999;180(2):483–90.
Harding A, Dreosti IE, Tulsi RS. Zinc deficiency in the 11 day rat embryo: a scanning and transmission electron microscope study. Life Sci. 1988;42:889–96.
McKenzie J, Fosmire GJ, Sandstead HH. Zinc deficiency during the latter third of pregnancy: effects on fetal rat brain, liver, and placenta. J Nutr. 1975;105(11):1466–75.
Wang F, Bian W, Kong LW, et al. Maternal zinc deficiency impairs brain nesting expression in prenatal and postnatal mice. Cell Res. 2001;11(2):135–41.
Halas E, Hanlon M. Intrauterine nutrition and aggression. Nature. 1975;257:221.
Halas E, Sandstead HH. Some effects of prenatal zinc deficiency on behavior of the adult rat. Pediatr Res. 1975;9(2):94–7.
Halas E, Hunt CD, Eberhardt MJ. Learning and memory disabilities in young adult rats from mildly zinc deficient dams. Physiol Behav. 1986;37:451–8.
Bruno R, Song Y, Leonard SW, et al. Dietary zinc restriction in rats alters antioxidant status and increases plasma F2 isoprostanes. J Nutr Biochem. 2007;18:509–18.
Ho E, Ames BN. Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFkB, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line. Proc Natl Acad Sci U S A. 2002;99(26):16770–5.
Ho E. Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem. 2004;15:572–8.
Castro C, Kaspin LC, Chen SS, et al. Zinc deficiency increases the frequency of single-strand DNA breaks in rat liver. Nutr Res. 1992;12:721–36.
Olin K, Shigenaga MK, Ames BN, et al. Maternal dietary zinc influences DNA strand break and 8-hydroxy-2-deoxyguanosine levels in infant rhesus monkey liver. Proc Soc Exp Biol Med. 1993;203:461–6.
Bestor T. Activation of mammalian DNA methyltransferase by cleavage of a ZN binding regulatory domain. EMBO J. 1992;11(7):2611–7.
Salozhin S, Prokhorchuck EB, Georgiev GP. Methylation of DNA—one of the major epigenetic markers. Biochemistry. 2005;70(5):525–32.
Ohlsson R, Renkawitz R, Lobanenkov V. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 2001;17(9):520–7.
Loukinov D, Pugacheva E, Vatolin S, et al. BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc Natl Acad Sci U S A. 2002;99(10):6806–11.
Chowanadisai W, Lönnerdal B, Kelleher SL. Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. J Biol Chem. 2006;281(51):39699–707.
Wang K, Zhou B, Kuo YM, et al. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet. 2002;71:66–73.
Susser E, Brown AS, Gorman JM. Prenatal exposures in schizophrenia. Arlington: American Psychiatric Publishing; 1999.
van der Put N, van Straaten HWM, Trijbels FJM, et al. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med. 2001;226:243–70.
Nisha A, Numata S, Tajima A, et al. Meta-analysis of blood homocysteine levels for gender and genetic association studies of MTHFR C677T polymorphism in Schizophrenia. Schizophr Bull. 2014;40:1154–63.
Fenech M. The role of folic acid and Vitamin B12 in genomic stability of human cells. Mutat Res. 2001;475(1–2):57–67.
Teo T, Fenech M. The interactive effect of alcohol and folic acid on genome stability in human WIL2-NS cells measured using the cytokinesis-block micronucleus cytome assay. Mutat Res. 2008;657(1):32–8.
Bagnyukova TV, Powell CL, Pavliv O, et al. Induction of oxidative stress and DNA damage in rat brain by a folate/methyl-deficient diet. Brain Res. 2008;1237:44–51.
Young S, Eskenazi B, Marchetti FM, et al. The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod. 2008;23(5):1014–22.
Boxmeer J, Smit M, Utomo E, et al. Low folate in seminal plasma in associated with increased sperm DNA damage. Fertil Steril. 2009;92(2):548–56.
Pembrey ME, Bygren LO, Golding J. The nature of human transgenerational responses. In: Jirtle HJ, Tyson FL, editors. Environmental epigenomics in health and disease epigenetics and disease origins. Heidelberg: Springer; 2013. p. 257–71.
Wolff G, Kodell RL, Moore SR, et al. Maternal epigenetics and methyl supplements affect agoutigene expression in Avy/amice. FASEB J. 1998;12:949–57.
Cooney C, Dave AA, Wolff GL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J Nutr. 2002;132:S2393–400.
Brown AS, Bottiglieri T, Schaefer CA, et al. Elevated prenatal homocysteine levels as a risk factor for schizophrenia. Arch Gen Psychiatry. 2007;64:31–9.
Suren P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid supplements and risk of autism spectral disorders in children. JAMA. 2013;309(6):570–7.
Roth C, Magnus P, Schjolberg S, Stoltenburg C, et al. Folic acid supplements in pregnancy and severe language delay in children. J Am Med Assoc. 2011;306:1566–73.
Schmidt RJ, Hansen RL, Hartiala J, et al. Prenatal vitamins, one-carbon metabolism gene variants, and risk of autism. Epidemiology. 2011;22:476–85.
Milne D, Canfield WK, Mahalko JR, et al. Effect of oral folic acid supplements on zinc, copper, and iron absorption and excretion. Am J Clin Nutr. 1984;39:535–9.
Ghishan F, Said HM, Wilson PC, et al. Intestinal transport of zinc and folic acid: a mutual inhibitory effect. Am J Clin Nutr. 1986;43:258–62.
Keizer S, Gibson RS, O’Connor DL. Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition. Am J Clin Nutr. 1995;62:377–84.
Davis C, Uthus EO. Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats. J Nutr. 2003;133:2907–14.
Vanderpas J, Contempré B, Duale NL, et al. Iodine and selenium deficiency associated with cretinism in northern Zaire. Am J Clin Nutr. 1990;52:1087–93.
Vanderpas J, Contempré B, Duale NL, et al. Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects. Am J Clin Nutr. 1993;57(S2):S271–5.
Ruz M, Codoceo J, Galgani J, et al. Single and multiple selenium-zinc-iodine deficiencies affect rat thyroid metabolism and ultrastructure. J Nutr. 1998;129(1):174–80.
Brown AS, Begg MD, Gravenstein S, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 2004;61(8):774–80.
Brown AS, Begg MD, Gravenstein S, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Obstet Gynecol Surv. 2005;60(2):77–8.
Mortensen P, Nørgaard-Pedersen B, Waltoft BL, et al. Early infections of Toxoplasma gondii and the later development of schizophrenia. Schizophr Bull. 2007;33(3):741–4.
Sørensen H, Mortensen EL, Reinisch JM, et al. Association between prenatal exposure to bacterial infection and risk of schizophrenia. Schizophr Bull. 2009;35(3):631–7.
Meyer U, Feldon J, Yee BK. A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophr Bull. 2008. doi:10.1093/Schbul/sbno22.epub.
Wellinghausen N. Immunobiology of gestational zinc deficiency. Br J Nutr. 2001;85(S2):S81–6.
Caulfield L, Zavaleta N, Shankar AH, et al. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr. 1998;68:499S–508.
Beck M, Nelson HK, Shi Q, et al. Selenium deficiency increases the pathology of an influenza virus infection. FASEB J. 2001;15:1481–3.
Food Standards Agency (2003). Report N05012: Functional markers of selenium in man. http://www.foodstandards.gov.uk/science/research/researchinfo/nutritionresearch/optimalnutrition/n05programme/n05listbio/n05012/. Accessed 19 Oct 2008.
Broome C, McArdle F, Kyle JA, et al. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr. 2004;80:154–62.
Brown K. Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries. Am J Clin Nutr. 1998;S68:S425–9.
Tomkins A. Assessing micronutrient status in the presence of inflammation. J Nutr. 2003;133:S1649–55.
Duggan C, MacLeod WB, Krebs NF, et al. Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria. J Nutr. 2005;135:802–7.
Magnus P, Irgens LM, Haug K, et al. Cohort profile: the Norwegian mother and child study. Int J Epidemiol. 2006;35(5):1145–50.
Branum A, Collman GW, Correa A, et al. The National Children’s study of environmental effects on child development. Environ Health Perspect. 2003;111(4):642–6.
Couzin Frankel J. Science gold mine, ethics minefield. Science. 2009;234:166–8.
Susser E, St. Clair D, He L. Latent effects of prenatal malnutrition on adult health: the example of schizophrenia. In: Kaler SG, Rennert OM, editors. Reducing the impact of poverty on health and human development: scientific approaches. Boston: Blackwell Publishing on behalf of the New York Academy of Sciences; 2008. p. 185–92.
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This chapter is an updated and expanded version of a previous article [133] The authors thank Kim Fader for her help and the Robert Wood Johnson Health & Society Scholars Program for its financial support.
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St. Clair, D., Susser, E. (2015). Linking Prenatal Nutrition to Adult Mental Health. In: Bendich, A., Deckelbaum, R. (eds) Preventive Nutrition. Nutrition and Health. Springer, Cham. https://doi.org/10.1007/978-3-319-22431-2_34
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