Maternal Famine, De Novo Mutations, and Schizophrenia
- Jack M. McClellan, MD;
- Ezra Susser, MD, DrPH;
- Mary-Claire King, PhD
- Author Affiliations: Department of Psychiatry, University of Washington, Seattle (Dr McClellan); Department of Epidemiology, Mailman School of Public Health, Columbia University, and New York State Psychiatric Institute, New York (Dr Susser); and Departments of Genome Sciences and Medicine (Medical Genetics), University of Washington, Seattle (Dr King).
- Corresponding Author: Jack M. McClellan, MD, Department of Psychiatry, University of Washington, Box 356560, Seattle, WA 98195 (drjack{at}u.washington.edu).
Since this article does not have an abstract, we have provided the first 150 words of the full text.
- KEYWORDS:
- FOLIC ACID
- GENE EXPRESSION
- MATERNAL NUTRITION
- MUTATION
- PREGNANCY
- PRENATAL EXPOSURE DELAYED EFFECTS
- SCHIZOPHRENIA
- STARVATION
Schizophrenia is a debilitating neuropsychiatric disorder that likely stems from multiple genetic and environmental factors.1 Identifying molecular mechanisms underlying schizophrenia offers the promise of improved treatment and prevention strategies. Finding culprit mutations and the genes that harbor them is therefore one of the great challenges of human genomics.
Studying populations who survived in utero exposure to maternal starvation may reveal clues regarding the genetic bases of schizophrenia. For example, epidemiological investigations of 2 famines in the 20th century—the Nazi-induced 1944-1945 Dutch Hunger Winter2 and the Chinese famine of 1959-1961 following the failure of the Great Leap Forward3—demonstrated an increased risk for schizophrenia among offspring conceived in famine conditions. A possible molecular basis for this risk may be the occurrence of new mutations in genes critical for brain development. Furthermore, folate deficiency, which could occur in famine, may be a mediator of this risk by impairing capacity …
