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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- "Environmental conditions during early life may amplify individual vulnerability to psychiatric disease later in life, especially in those with a genetic susceptibility to a specific disease (Bale et al., 2010; Gluckman et al., 2008; Rutter, 2005). Multiple studies have reported an association between bipolar disorder and stressful early life events such as gestational hunger (Brown et al., 2000), gestational influenza (Machon et al., 1997; Parboosing et al., 2013), childhood abuse (Daglas et al., 2014; Etain et al., 2008; Gilman et al., 2014) and early parental loss (Mortensen et al., 2003). Early life events that may induce circadian dysfunction are of particular interest since bipolar disorder involves the disruption of many biological rhythms affecting the 24 h sleepewake cycle, energy and alertness (Giglio et al., 2009; McClung, 2013; Murray and Harvey, 2010; Wirz-Justice, 2006). "
ABSTRACT: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life. Copyright © 2015 Elsevier Ltd. All rights reserved.Journal of Psychiatric Research 03/2015; 64. DOI:10.1016/j.jpsychires.2015.03.013 · 4.09 Impact Factor
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ABSTRACT: Pregnant women infected with influenza virus are more likely to experience severe complications when compared with their non-pregnant peers. Yet influenza vaccine uptake is low among pregnant women. The purpose of this study was to assess the prevalence of seasonal influenza vaccine uptake among pregnant women in Hong Kong and to identify predictors of vaccine uptake. Using a multi-center cross-sectional design, we recruited 2822 new mothers during their immediate postpartum stay from all eight public obstetric hospitals in Hong Kong. We assessed antenatal maternal influenza vaccination status as well as health beliefs and perceptions toward influenza and influenza vaccination. Bivariable and multivariable logistic regression was used to identify the predictors of vaccination uptake. Only 49 (1.7%; 95% CI 1.3-2.3%) participants were vaccinated during their pregnancy. Fear that the vaccine would cause harm to the fetus or themselves were the most common reasons for not being vaccinated. Being aware of the vaccination recommendations (OR=2.69; 95% CI 1.06, 6.82), being advised by a health-care provider (OR=6.30; 95% CI 3.19, 12.46), history of vaccination (OR=2.47; 95% CI 1.25, 4.91), perceived susceptibility to influenza infection (OR=3.67; 95% CI 1.64, 8.22), and perceived benefits of influenza vaccination (OR=9.98; 95% CI 3.79, 26.24) were all independently associated with vaccination. Perceived barriers to vaccination (OR=0.17; 95% CI 0.07, 0.40) were strongly associated with failure to vaccinate. Low seasonal influenza vaccination uptake among Hong Kong pregnant women was related to a number of factors, all of which are amenable to interventions. Vaccination promotion strategies need to focus on encouraging health-care providers to discuss vaccination with their pregnant clients and in providing pregnant women with accurate and unbiased information about the risks of influenza infection and the benefits of vaccination.Vaccine 09/2013; 31(45). DOI:10.1016/j.vaccine.2013.08.063 · 3.49 Impact Factor
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ABSTRACT: Bipolar disorder (BD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction is thought to play a key etiopathogenic role. In particular, excess of winter births associated with early-life infections raise the possibility of the implication of innate immunity. Given the pivotal role of Toll-like receptor 4 (TLR-4), a major innate immune sensor molecule, we hypothesized that genetic variations of TLR-4 may be associated to BD. Genomic DNAs from 572 BD patients and 202 healthy controls (HC) were analyzed for the distribution of six single nucleotides polymorphisms (SNPs) scattered along the TLR-4 locus (rs1927914, rs10759932, rs4986790, rs4986791, rs11536889 and rs11536891). Associations between BD and these polymorphisms were examined using the Chi-square test. We found that rs1927914 AA and rs11536891 TT genotype are more frequent in BD patients than in controls (corrected p; pc=.02 and .02 respectively) particularly in early-onset BD patients (pc=.004 and .006) born during the summer season (pc=.02 and .002 respectively). We also found that rs4986790 AG and rs4986791 CT genotypes were significantly associated with presence of autoimmune thyroiditis (pc=.002). Our results are to be confirmed by replication in independent BD cohorts. We report for the first time a genetic association between BD and TLR-4 a major player of innate immunity. Possible mechanisms underlying bipolar disorders linking altered TLR-4 expression and increased susceptibility to infections and/or autoimmunity are discussed.Journal of Affective Disorders 10/2013; 152. DOI:10.1016/j.jad.2013.09.043 · 3.71 Impact Factor