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.
"Maternal infectious or inflammatory insults during pregnancy have been repeatedly implicated in the etiology of developmental neuropsychiatric disorders, including schizophrenia (Brown and Derkits, 2010; Canetta et al., 2014b), autism (Atladóttir et al., 2012; Brown et al., 2014), and bipolar disorder (Canetta et al., 2014a; Parboosing et al., 2013). Preclinical support for these epidemiological associations has been obtained by various translational rodent models demonstrating multiple brain and behavioral abnormalities following prenatal exposure to infection and/or immune activation (reviewed in Boksa (2010), Harvey and Boksa (2012), Meyer (2014), Meyer and Feldon (2010)). "
[Show abstract][Hide abstract] ABSTRACT: Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre- and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1β levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation.
Brain Behavior and Immunity 09/2015; DOI:10.1016/j.bbi.2015.09.015 · 5.89 Impact Factor
"Thus, the other ideal model would be an animal model that is created by gene-environment interaction, in which a genetic model of a common polymorphism is exposed to an environmental risk factor interacting with the polymorphism. Among environmental factors, perinatal infection (Parboosing et al., 2013), maternal smoking during pregnancy (Talati et al., 2013), and perinatal complications are established risk factors for bipolar disorder, but also apply to schizophrenia (Schmitt et al., 2014). Childhood maltreatment also is a common risk factor for depression and bipolar disorder (Daruy-Filho et al., 2011) as well as other mental disorders, such as personality and anxiety disorders. "
"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). "
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