Gestational Influenza and Bipolar Disorder in Adult Offspring
ABSTRACT 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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ABSTRACT: Consistent evidence has linked a range of prenatal maternal infections with psychotic disorders in later life. However, the potential for this exposure to impact more common disorders requires further investigation. Participants came from the Mater University Study of pregnancy, a longitudinal, pre-birth cohort study which recruited pregnant mothers from a Brisbane hospital between 1981 and 1984. At age 21, 2439 offspring completed the CIDI-Auto. Multivariate logistic regression was used to investigate associations of self-reported symptoms of prenatal infection with a range of DSM-IV anxiety and affective diagnoses, while also testing for gender interactions. In multivariate analyses, self-reported symptoms of prenatal genital infection predicted Post-traumatic stress disorders (OR=2.38, 95% CI: 1.14, 4.95) and social phobias (OR=1.93, 95% CI: 1.03, 3.61), in addition to evidence for a gender interaction by which males (OR=6.04, 95% CI: 2.00, 18.30) but not females were at greater risk for PTSD. Further analyses among those with PTSD revealed the relationship to be stronger when excluding those not exposed to trauma (OR=3.21, 95% CI: 1.53, 6.72). We were unable to clinically or serologically verify the presence and the type of prenatal genital infection. This is the first study to show an association between self-reported symptoms of prenatal genital infections and two highly prevalent anxiety disorders among adult offspring. The relationship with PTSD was particularly strong and suggested that the exposure may primarily impact PTSD in males. Further research with the capacity to assess a fuller-range of specific prenatal infections is warranted to evaluate the potential of reducing the prevalence of these disorders. Copyright © 2015 Elsevier B.V. All rights reserved.Journal of Affective Disorders 01/2015; 175C:241-247. DOI:10.1016/j.jad.2015.01.011 · 3.76 Impact Factor
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ABSTRACT: Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment.05/2014; 4:e434. DOI:10.1038/tp.2014.80
01/2014; 2014. DOI:10.1155/2014/867805