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Articles   |    
Serological Documentation of Maternal Influenza Exposure and Bipolar Disorder in Adult Offspring
Sarah E. Canetta, Ph.D.; Yuanyuan Bao, M.S.; Mary Dawn T. Co, M.D.; Francis A. Ennis, M.D.; John Cruz, B.S.; Masanori Terajima, M.D., Ph.D.; Ling Shen, Ph.D.; Christoph Kellendonk, Ph.D.; Catherine A. Schaefer, Ph.D.; Alan S. Brown, M.D., M.P.H.
Am J Psychiatry 2014;171:557-563. doi:10.1176/appi.ajp.2013.13070943
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Supported by NIMH grants 5R01 MH073080, 5K02 MH065422, 5R01 MH069819, and T32 MH16434-31; National Institute on Child Health and Development grants N01-HD-1-3334 and NO1-HD-6-325; and National Institute of Allergy and Infectious Diseases grant U19 AI-057319.

Dr. Co has received funding from GlaxoSmithKline, the National Institute of Allergy and Infectious Diseases, Sanofi-Pasteur Biologics, and Walter Reed Army Institute of Research. Drs. Ennis, Cruz, and Terajima have received funding from GlaxoSmithKline, the National Institute of Allergy and Infectious Diseases, and Walter Reed Army Institute of Research. The other authors report no financial relationships with commercial interests.

From the Department of Psychiatry, Columbia University College of Physicians and Surgeons, N.Y. State Psychiatric Institute, N.Y.; the Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Mass., the Division of Research, Kaiser Permanente, Oakland, Calif.; and the Department of Epidemiology, Mailman School of Public Health, Columbia University, N.Y.

Presented in part at the 14th International Congress of Schizophrenia Research, Orlando, Fla., April 21–25, 2013.

Address correspondence to Dr. Brown (asb11@columbia.edu).

Copyright © 2014 by the American Psychiatric Association

Received July 17, 2013; Revised September 30, 2013; Accepted October 25, 2013.

Abstract

Objective  The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features.

Method  The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay.

Results  No association was observed between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serological influenza exposure was related to a significant fivefold greater risk of bipolar disorder with psychotic features.

Conclusions  The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, these results may suggest that prenatal influenza is a risk factor for psychosis rather than for a specific psychotic disorder diagnosis.

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TABLE 1.Characteristics of Analytic Sample in a Study of Maternal Influenza and Bipolar Disorder in Offspring
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a Data missing for one case subject.

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b Data missing for six case subjects and nine comparison subjects.

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c Maternal psychiatric disorder was defined as psychoses, schizophrenia, affective disorder, anxiety, alcohol/substance abuse, mental deficiency, or other mental disorders. Data missing for one case subject and one comparison subject.

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TABLE 2.Characteristics and Serological Evidence of Influenza Exposure in a Study of Maternal Influenza and Bipolar Disorder in Offspring
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a Data missing for one unexposed individual.

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b Data missing for one exposed individual.

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c Data missing for seven exposed and eight unexposed individuals.

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d Maternal psychiatric disorder was defined as psychoses, schizophrenia, affective disorder, anxiety, alcohol/substance abuse, mental deficiency, and other mental disorders. Data missing for two unexposed individuals.

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TABLE 3.Serological Evidence of Maternal Exposure to Influenza and Risk of Bipolar Disorder in Offspring
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TABLE 4.Serological Evidence of Maternal Exposure to Influenza by Trimester and Risk of Bipolar Disorder With Psychotic Features in Offspring
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TABLE 5.Composite Measure of Exposure to Maternal Influenza During Pregnancy and Risk of Bipolar Disorder in Offspringa
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a Defined as serological evidence of maternal exposure to influenza or a clinical diagnosis of influenza during pregnancy.

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