Neonatal antibodies to infectious agents and risk of bipolar disorder: a population-based case-control study.

OBJECTIVE: There is a substantial evidence base linking prenatal exposure to infectious agents and an increased risk of schizophrenia. However, there has been less research examining the potential for these exposures to also contribute to risk for bipolar disorder. The aim of this study was to examine the association between neonatal markers of selected prenatal infections and risk for bipolar disorder. METHODS: Using population-based Danish registers, we examined 127 individuals with a diagnosis of bipolar disorder, and 127 sex and day-of-birth individually matched controls. Based on neonatal dried blood spots, we measured antibodies to herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), and Toxoplasma gondii. Relative risks were calculated for the matched pairs when examined for optical density units for antibodies to each of the infectious agents. RESULTS: There was no association between any of the neonatal markers of prenatal infection and risk of bipolar disorder. CONCLUSIONS: In contrast with studies of schizophrenia, our analysis does not support maternal infection with HSV-1, HSV-2, CMV, or Toxoplasma gondii as risk factors for bipolar disorder. However, larger study samples are needed, and data on, for example, specific serotypes of Toxoplasma and indicators of the timing of maternal infection are still warranted.

A Danish National Birth Cohort study of maternal HSV-2 antibodies as a risk factor for schizophrenia in their offspring.

BACKGROUND: Several studies have implicated early infections, including maternal infection with herpes simplex virus 2 (HSV-2), as an environmental risk factor for schizophrenia. METHODS: A case-control study nested within the national Danish birth cohort constituted by the PKU Biobank covering all children born in Denmark since 1981. 602 cases of schizophrenia (ICD-10 F20) were ascertained in the Danish Psychiatric Central Register, covering all in- and out-patient contacts in Denmark, and 602 controls were matched individually on gender, exact date of birth and living in Denmark on the date the case became a case. Incidence rate ratio for schizophrenia was estimated using conditional logistic regression. Main exposure was HSV-2 IgG antibody levels. Confounders and potential interacting factors included family history of mental illness, place of birth and gestational age at time of birth. RESULTS: Elevated levels of maternal HSV-2 IgG were associated with schizophrenia risk (IRR 1.56; 95% CI 1.17-2.07, p=0.002). This association was not confounded by a maternal or sibling history of psychiatric illness, place of birth, parental age, gestational age, or immigrant status of the parents. However, adjustment for paternal psychiatric history reduced risk slightly (IRR 1.43; 95% CI 1.06-1.92, p=0.02). CONCLUSIONS: The study replicates an association between maternal HSV-2 IgG levels and schizophrenia risk. Since the confounding by familial risk factors is confined to paternal mental illnesses not belonging to the schizophrenia spectrum, we hypothesize that this confounding may be partly due to other risk factors, e.g., other sexually transmitted infections, rather than reflecting variations in genetic liability to develop schizophrenia.