Maternal viral infection during pregnancy is a risk factor for schizophrenia.1 But there has been relatively less research on the association between maternal bacterial infection during pregnancy and psychosis risk. Maternal infections may include forms of sexually transmitted disease (STD), some viral respiratory and bacterial infections, toxoplasmosis. One study found that maternal bacterial infection was associated with a two-fold increase in schizophrenia risk.2 Findings from another study suggest an association between pyelonephritis and risk of psychosis.3 Moreover, gestational immune disruption may disproportionately affect males with regards to psychosis risk.4
Lee and colleagues5 investigated the association between maternal bacterial infections during pregnancy and psychosis risk, including potential moderating effects of sex and parental history of psychiatric illness. They considered 16,188 live births enrolled between 1959 and 1966 at the Boston and Providence sites of the Collaborative Perinatal project, currently known as the New England Family Study. Parents and offspring (who are now in their 50s) with psychotic disorders were identified.
A total of 15,421 participants were included in the final analytic sample. Data on infectious disease exposures were collected at regular prenatal visits. The primary exposure variable was any bacterial infection during pregnancy. If women had multiple infections, they were counted only once. Infections affecting more than one major organ system were defined as multisystemic (eg, sepsis), and those affecting one system were defined as localized (eg, vaginitis).
Cohort members with psychosis were identified at ages 32 to 39 years through a systematic follow-up. Affected parents and offspring were identified via record linkage, direct interview, and subject self-report. After systematic follow-up and structured clinical interviews, 116 adult offspring were found to have a nonorganic psychotic disorder (n = 52 schizophrenia or schizoaffective disorder, depressed type; and n = 53 schizoaffective disorder, bipolar type, or mood disorder with psychotic features; n = 11 delusional disorder, brief psychotic disorder, or psychotic disorder not otherwise specified).
The researchers included maternal race, study site, maternal education, parental socioeconomic index, year and season of birth, parental psychiatric history, and maternal viral infection during pregnancy as covariates. Logistic regression was used to estimate the odds of psychosis for maternal exposure to bacterial infection during pregnancy, adjusting for these covariates. The authors also examined effect modification by offspring sex and parental mental illness. They also performed sensitivity analyses considering only confirmed bacterial infection (by antibiotic treatment and/or physician diagnosis).
The researchers identifies 399 (3%) multisystemic and 3191 (21%) localized infections during pregnancy. Localized infections included vaginitis, urinary tract infections, pneumonia, syphilis, gonorrhea, and tuberculosis. Maternal bacterial infection was associated with a significant increased odds of psychosis (adjusted OR = 1.8; 95% CI, 1.2-2.7), with stronger effects for multisystemic (OR = 2.9; 95% CI, 1.3-5.9) compared with localized (OR = 1.6; 95% CI, 1.1-2.3) infections. Furthermore, the association between maternal bacterial infection and psychosis risk was modified by offspring sex.
Psychotic disorders were 3-fold more likely to develop in males after maternal infection (OR = 2.6; 95% CI, 1.6-4.2), whereas there was no difference in females (OR = 1.0; 95% CI, 0.5-1.9). The pattern of findings was similar when considering localized bacterial infections. Additionally, in sensitivity analysis, the association remained significant and with slightly greater magnitude. By contrast, the association was not moderated by parental mental illness.
The authors concluded that maternal bacterial infection during pregnancy was significantly associated with the development of schizophrenia and related psychoses among offspring, with stronger effects for multisystemic than localized infections, and in males. Findings underscore the potential role of maternal bacterial infections during pregnancy in the etiology of psychosis.
The strength of the study is the systematically collected prospective data in this birth cohort. The authors noted potential misclassification of exposure and interactions between infection and other non-biological factors (eg, socioeconomic status) as study limitations.
The bottom line
Maternal bacterial infections during pregnancy are associated with risk of psychosis in the offspring, which is moderated by the severity of infection and gender. Future, larger samples are needed to address components of the potential etiologic pathway regarding this connection, including gestational timing of exposure and sex-specific transmission. Replicated findings would underscore the need for public health and clinical effects to reduce psychosis risk by preventing and managing bacterial infection in pregnant women.
Dr Miller is Associate Professor of Psychiatry, Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is the Schizophrenia Section Editor for Psychiatric Times. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.
1. Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010;167:261-280.
2. Sørensen HJ, Mortensen EL, ReinischJM, et al. Association between prenatal exposure to bacterial infection and risk of schizophrenia. Schizophr Bull. 2009;35:631-637.
3. Clarke MC, Tanskanen A, Huttunen M, et al. Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia. Am J Psychiatry. 2009;166:1025-1030.
4. Goldstein JM, Cherkerzian S, Seidman LJ, et al. Prenatal maternal immune disruption and sex-dependent risk for psychoses. Psychol Med. 2014;44:3249-3261.
5. Lee YH, Cherkerzian S, Seidman LJ, et al. Maternal bacterial infection during pregnancy and offspring risk of psychotic disorders: variation by severity of infection and offspring sex. Am J Psychiatry. October 4, 2019 ;Epub ahead of print.