Infection during childhood and the risk of violent criminal behavior in adulthood.

Infections during brain development appear to contribute to cognitive impairment and aggressive behavior, as well as to a number of developmental mental disorders closely associated with violent criminal behavior. Yet, no study has thus far ever investigated whether infections during brain development increases the risk of violent criminality later in life. In this population-based cohort study, about 2.2 million individuals born in Sweden between the years 1973 and 1995 were included in an effort to estimate the association between infections during childhood (registered ICD-10 diagnoses of infections incurred before the age of 14 years) and violent criminal behavior (registered convictions for a violent crime between the ages of 15 and 38 years, prior to December 31, 2011). After inclusion of several sociodemographic parameters, risks of violent criminal behavior conferred by childhood infections - expressed as hazard ratios (HRs) and 95% confidence intervals (CIs) - were calculated by means of Cox regression. Mediation analyses were performed to explore the effect of psychiatric disorders on the association between infections during childhood and violent criminality. Results revealed a modest, yet significant, association between an infection during childhood and violent criminality later in life (adjusted HR 1.14, 95% CI 1.12-1.16). Infections during the first year of life and infections in the central nervous system were associated with the highest risks of subsequent violent criminality (adjusted HR 1.20, 95% CI 1.18-1.23, and adjusted HR 1.17, 95% CI 1.08-1.26, respectively). The association was partly mediated by the presence of a psychiatric disorder. In summary, independent of a wide range of covariates, our results suggest that infections during brain development could be part of the genesis of violent criminal behavior.

Associations Between Maternal Infection During Pregnancy, Childhood Infections, and the Risk of Subsequent Psychotic Disorder--A Swedish Cohort Study of Nearly 2 Million Individuals.

OBJECTIVE: Recent studies question whether the risk for psychotic disorder associated with prenatal exposure to infection are due to infections per se, or to shared susceptibility of both infections and psychiatric disorders. Moreover, the potential link between prenatal infection and serious infections during childhood, another alleged risk factor for psychotic disorder, remains unknown. The aim of this study was to investigate the role of maternal infections during pregnancy in context of parental psychiatric disorders and subsequent childhood infections. METHOD: All children born in Sweden 1978-1997 were linked to the National Patient Register. Hazard ratios of nonaffective psychosis were estimated in relation to maternal infection during pregnancy and odds ratios of childhood infection were calculated in relation to maternal infection during pregnancy. Relative excess risk due to interaction (RERI) estimated biological synergism between parental psychiatric disorder and maternal infection during pregnancy, and between maternal infection during pregnancy and childhood infection. RESULTS: Maternal infection during pregnancy was not statistically significantly associated with offspring psychosis (adjusted hazard ratio: 1.06, 95% CI 0.88-1.27). However, maternal infection during pregnancy and maternal psychiatric disorders acted synergistically in offspring psychosis development (RERI 1.33, 95% CI 0.27-2.38). Maternal infection during pregnancy increased the risk of offspring childhood infections (OR 1.50, 95% CI 1.45-1.54). These 2 factors also interacted in psychosis development (RERI 0.63, 95% CI 0.12-1.14). CONCLUSIONS: Among mothers with a history of psychiatric disease, infection during pregnancy increases the risk of psychosis in offspring. Maternal infections during pregnancy appear to contribute to the risk of childhood infections, which together render the child more vulnerable to psychosis development.

Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders.

Animal models indicate that maternal infection during pregnancy can result in behavioral abnormalities and neuropathologies in offspring. We examined the association between maternal inpatient diagnosis with infection during pregnancy and risk of ASD in a Swedish nationwide register-based birth cohort born 1984-2007 with follow-up through 2011. In total, the sample consisted of 2,371,403 persons with 24,414 ASD cases. Infection during pregnancy was defined from ICD codes. In the sample, 903 mothers of ASD cases (3.7%) had an inpatient diagnosis of infection during pregnancy. Logistic regression models adjusted for a number of covariates yielded odds ratios indicating approximately a 30% increase in ASD risk associated with any inpatient diagnosis of infection. Timing of infection did not appear to influence risk in the total Swedish population, since elevated risk of ASD was associated with infection in all trimesters. In a subsample analysis, infections were associated with greater risk of ASD with intellectual disability than for ASD without intellectual disability. The present study adds to the growing body of evidence, encompassing both animal and human studies, that supports possible immune-mediated mechanisms underlying the etiology of ASD.

Hospital admission with infection during childhood and risk for psychotic illness--a population-based cohort study.

A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0-13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03-1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08-1.40). Bacterial infections and central nervous system infections during preadolescence (10-13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21-2.05) and HR 1.96 (95% CI 1.05-3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors.

Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring--a matched case-control study.

BACKGROUND: An increasing number of studies suggest that certain maternal infections are associated with non-affective psychoses in the offspring. Here we investigated if maternal exposure to Toxoplasma gondii, cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) prior to delivery was associated with future diagnosis of schizophrenia or other non-affective psychoses in the offspring. METHODS: This case-control study included 198 individuals born in Sweden 1975-85, diagnosed with schizophrenia (ICD-10, F20) and other non-affective psychoses (ICD-10, F21-29) as in- or outpatients, and 524 matched controls. Specific immunoglobulin G (IgG) levels in archived neonatal dried blood samples from these individuals were determined by immunoassays. Reference levels were determined by prevalences among pregnant women in Sweden 1975-85. Odds ratios (OR) for schizophrenia and other non-affective psychoses were calculated, considering maternal and gestational factors as covariates. RESULTS: Levels of IgG directed at T. gondii corresponding to maternal exposure was associated with subsequent schizophrenia (OR=2.1, 95% CI 1.0-4.5) as were levels of IgG directed at CMV (OR=2.2, 95% CI 1.0-5.1) but not at HSV-1 or -2. There were even stronger associations with higher levels of T. gondii or CMV antibodies. There were no associations between any of the infectious agents and other non-affective psychoses. CONCLUSIONS: This study supports findings of maternal exposure to T. gondii and schizophrenia risk in offspring, and extends the risk to also include maternal exposure to CMV. Future studies should confirm the association with CMV exposure and identify mechanisms underlying these associations.

Maternal antibodies to dietary antigens and risk for nonaffective psychosis in offspring.

OBJECTIVE: The authors analyzed archival dried blood spots obtained from newborns to assess whether levels of immunoglobulin G (IgG) directed at dietary antigens were associated with a later diagnosis of a nonaffective psychotic disorder. METHOD: The study population consisted of individuals born in Sweden between 1975 and 1985 with verified register-based diagnoses of nonaffective psychoses made between 1987 and 2003 and comparison subjects matched on sex, date of birth, birth hospital, and municipality. A total of 211 case subjects and 553 comparison subjects consented to participate in the study. Data on factors associated with maternal status, pregnancy, and delivery were extracted from the Swedish Medical Birth Register. Levels of IgG directed at gliadin (a component of gluten) and casein (a milk protein) were analyzed in eluates from dried blood spots by enzyme-linked immunosorbent assay. Odds ratios were calculated for levels of IgG directed at gliadin or casein for nonaffective psychosis. RESULTS: Levels of anti-gliadin IgG (but not anti-casein IgG) above the 90th percentile of levels observed among comparison subjects were associated with nonaffective psychosis (odds ratio=1.7, 95% CI=1.1-2.8). This association was not confounded by differences in maternal age, immigrant status, or mode of delivery. Similarly, gestational age at birth, ponderal index, and birth weight were not related to maternal levels of anti-gliadin IgG. CONCLUSIONS: High levels of anti-gliadin IgG in the maternal circulation are associated with an elevated risk for the development of a nonaffective psychosis in offspring. Research is needed to identify the mechanisms underlying this association in order to develop preventive strategies.