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Beverly J. Insel, DrPH; Catherine A. Schaefer, PhD; Ian W. McKeague, PhD; Ezra S. Susser, MD, DrPH; Alan S. Brown, MD, MPH

Arch Gen Psychiatry. 2008;65(10):1136-1144.

Context  Iron is essential for brain development and functioning. Emerging evidence suggests that iron deficiency in early life leads to long-lasting neural and behavioral deficits in infants and children. Adopting a life course perspective, we examined the effects of early iron deficiency on the risk of schizophrenia in adulthood.

Objective  To determine whether maternal iron deficiency, assessed by maternal hemoglobin concentration during pregnancy, increases the susceptibility to schizophrenia spectrum disorders (SSDs) among offspring.

Design  Data were drawn from a population-based cohort born from 1959 through 1967 and followed up for development of SSD from 1981 through 1997.

Participants  Of 6872 offspring for whom maternal hemoglobin concentration was available, 57 had SSDs (0.8%) and 6815 did not (99.2%).

Main Outcome Measure  Prospectively assayed, the mean value of maternal hemoglobin concentration was the primary exposure. Hemoglobin concentration was analyzed as a continuous and a categorical variable.

Results  A mean maternal hemoglobin concentration of 10.0 g/dL or less was associated with a nearly 4-fold statistically significant increased rate of SSDs (adjusted rate ratio, 3.73; 95% confidence interval, 1.41-9.81; P = .008) compared with a mean maternal hemoglobin concentration of 12.0 g/dL or higher, adjusting for maternal education and ethnicity. For every 1-g/dL increase in mean maternal hemoglobin concentration, a 27% decrease in the rate of SSDs was observed (95% confidence interval, 0.55-0.96; P = .02).

Conclusions  The findings suggest that maternal iron deficiency may be a risk factor for SSDs among offspring. Given that this hypothesis offers the potential for reducing the risk for SSDs, further investigation in independent samples is warranted.

Author Affiliations: New York State Psychiatric Institute (Drs Insel, Susser, and Brown), Mailman School of Public Health (Drs Insel, McKeague, Susser, and Brown), and College of Physicians and Surgeons (Drs Susser and Brown), Columbia University, New York; and Division of Research, Kaiser Permanente, Oakland, California (Dr Schaefer).

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