Original Investigation |

Gestational Influenza and Bipolar Disorder in Adult Offspring

Raveen Parboosing, MBChB, MMed, FCPath(SA)(Viro), MS1; Yuanyuan Bao, MS2; Ling Shen, PhD4; Catherine A. Schaefer, PhD4; Alan S. Brown, MD, MPH2,3
[+] Author Affiliations
1Department of Virology, National Health Laboratory Service and University of KwaZulu-Natal, Albert Luthuli Central Hospital, Durban, South Africa
2Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York
3Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York
4Kaiser Permanente Division of Research, Oakland, California
JAMA Psychiatry. 2013;70(7):677-685. doi:10.1001/jamapsychiatry.2013.896.
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Importance  Gestational influenza has been associated previously with schizophrenia in offspring, but the relationship between this exposure and bipolar disorder (BD) is unclear. The identification of gestational influenza as a risk factor for BD may have potential for preventive approaches.

Objective  To test the hypothesis that maternal influenza during pregnancy is related to BD among offspring.

Design  Nested case-control study of a population-based birth cohort from the Child Health and Development Study (CHDS). From January 1, 1959, through December 31, 1966, the CHDS recruited nearly all pregnant women receiving obstetric care from the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC). Data on treated maternal influenza from the CHDS were used. Potential cases with BD from the cohort were identified by database linkages of identifiers among the CHDS, Kaiser Permanente database, and a large county health care database; by a mailed questionnaire to the CHDS cohort with subsequent interviews; and from an earlier psychiatric follow-up study on this birth cohort.

Setting  The CHDS, Kaiser Permanente, and county health care databases.

Participants  Cases of BD (n = 92) confirmed by structured research interviews and consensus diagnosis among the 214 subjects (48% of those ascertained) who participated and control subjects (n = 722) matched on date of birth, sex, and membership in KPNC or residence in Alameda County.

Exposures  Influenza.

Main Outcome and Measures  Bipolar I or II disorder, BD not otherwise specified, or BD with psychotic features.

Results  We found a significant, nearly 4-fold increase in the risk of BD (odds ratio, 3.82 [95% CI, 1.58-9.24; P = .003]) after exposure to maternal influenza at any time during pregnancy. The findings were not confounded by maternal age, race, educational level, gestational age at birth, and maternal psychiatric disorders.

Conclusions and Relevance  Maternal influenza may be a risk factor for BD. Although replication is required, the findings suggest that prevention of maternal influenza during pregnancy may reduce the risk of BD.

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Ascertainment of the Study Sample With Bipolar Disorder (BD)

*We used database linkages with the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC), the Alameda County Behavioral Health Care Services (ABHCS) (described in the Methods section), and subjects from the Child Health and Development Study (CHDS) cohort with screen-positive findings after a mailed questionnaire on mental health to mothers and offspring. We found overlap among the KPNC, ABHCS, and CHDS mailing sources and the Prenatal Determinants of Schizophrenia Study (PDS I). For each source, the numbers of cases found in at least 1 other source among the total number of cases were as follows: 22 of 50 in the KPNC, 14 of 24 in the ABHCS, 11 of 30 in the CHDS mailing, and 18 of 26 in the PDS I. For subjects ascertained on the basis of mailing to mothers and offspring in the CHDS cohort, surveys indicating mental health problems were returned by 535 subjects. Among these, the Family Interview for Genetic Studies was completed on 376 subjects, and of these, 80 subjects had positive findings for bipolar disorder or psychosis. All 80 were sought for interview. †Reasons include being deceased, incarcerated, or too ill (psychosis, severe mental disability) and not having permission from the physician.

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Submit a Comment
The Striatum Undergoes An Important Developmental Programme During the Second Trimester
Posted on May 14, 2013
Gabriela Novak
University of Toronto
Conflict of Interest: None Declared
Dear Dr. Brown: I read your publication with great interest. Your findings are in line with my observation that the striatum, a structure strongly involved in the etiology of schizophrenia, undergoes an important developmental program during the second trimester. This program involves is sensitive to immune activation. Some information is available in the following publication: http://www.ncbi.nlm.nih.gov/pubmed/23184870. See also the review at PMID 23313435.
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