Prenatal Nutritional Deficiency and Risk of Adult Schizophrenia

Alan S. Brown; Ezra S. Susser

Disclosures

Schizophr Bull. 2008;34(6):1054-1063. 

In This Article

Abstract and Introduction

Converging evidence suggests that a neurodevelopmental disruption plays a role in the vulnerability to schizophrenia. The authors review evidence supporting in utero exposure to nutritional deficiency as a determinant of schizophrenia. We first describe studies demonstrating that early gestational exposure to the Dutch Hunger Winter of 1944-1945 and to a severe famine in China are each associated with an increased risk of schizophrenia in offspring. The plausibility of several candidate micronutrients as potential risk factors for schizophrenia and the biological mechanisms that may underlie these associations are then reviewed. These nutrients include folate, essential fatty acids, retinoids, vitamin D, and iron. Following this discussion, we describe the methodology and results of an epidemiologic study based on a large birth cohort that has tested the association between prenatal homocysteine, an indicator of serum folate, and schizophrenia risk. The study capitalized on the use of archived prenatal serum specimens that make it possible to obtain direct, prospective biomarkers of prenatal insults, including levels of various nutrients during pregnancy. Finally, we discuss several strategies for subjecting the prenatal nutritional hypothesis of schizophrenia to further testing. These approaches include direct assessment of additional prenatal nutritional biomarkers in relation to schizophrenia in large birth cohorts, studies of epigenetic effects of prenatal starvation, association studies of genes relevant to folate and other micronutrient deficiencies, and animal models. Given the relatively high prevalence of nutritional deficiencies during pregnancy, this work has the potential to offer substantial benefits for the prevention of schizophrenia in the population.

Evidence from various domains of research indicates that a disturbance in early neurodevelopment may lead to a vulnerability to schizophrenia in adolescence or adulthood. Accumulating data have implicated the in utero environment in the etiology of this disorder.[1] In this article, we review and discuss the sources of evidence for testing hypotheses about the relation of prenatal nutritional deficiency to offspring risk of schizophrenia. The long interval between an exposure in the prenatal period and the risk of schizophrenia in adulthood and the difficulty of obtaining precise data on prenatal nutritional intake are among the considerable challenges faced by researchers in this field. Nonetheless, successful studies have been built around historic events, a design sometimes referred to as a "natural experiment."

We first describe studies linking prenatal exposure to the Dutch Hunger Winter of 1944-1945 with offspring schizophrenia and a recent worthy replication of this finding. We also discuss some of the candidate nutritional deficiencies that might explain the results from these studies. Next we describe how the intriguing findings from these studies can be pursued in birth cohorts followed up for schizophrenia, making use of archived biological specimens to measure prenatal nutritional status. Finally, we discuss the approaches being developed for more powerful tests of these hypotheses, focusing for illustrative purposes on the folate/homocysteine (hcy) pathway.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....