Joint Effects of Exposure to Prenatal Infection and Peripubertal Psychological Trauma in Schizophrenia

Abstract

Context: Prenatal infection and traumatizing experiences have both been linked with schizophrenia, but none of these factors seem sufficient to cause the disorder. However, recent evidence suggests that these environmental insults act in synergy to increase schizophrenia risk. Objective: To estimate the independent and joint effects of exposure to prenatal infection and peripubertal psychological trauma on the risk of schizophrenia. Design: Danish nationwide registers were linked in this prospective cohort study. We used survival analysis to report incidence rate ratios (IRRs) and corresponding 95% confidence intervals (95% CIs). Analyses were adjusted for age and calendar period and stratified by sex. Participants: A total of 979 701 persons born between 1980 and 1998 were followed up from January 1, 1995 through December 31, 2013, with 9656 having a hospital contact for schizophrenia. Results: Females exposed to prenatal infection had a significantly increased risk of schizophrenia (IRR: 1.61, 95% CI: 1.30-2.00), but not males (IRR: 0.99, 95% CI: 0.77-1.28). Peripubertal trauma was associated with increased risk in both sexes. Males, however, had a significantly higher risk of schizophrenia after exposure to both prenatal infection and peripubertal psychological trauma (IRR: 2.85, 95% CI: 2.32-3.51), with significant interaction between infection and peripubertal trauma on the multiplicative scale (P = .007). Conclusions: Our study demonstrated for the first time that prenatal infection and psychological trauma in peripubertal life can act in synergy to increase the risk of schizophrenia, with a potentially stronger susceptibility in males.

Maternal infection and stress during pregnancy and depressive symptoms in adolescent offspring

“…Preliminary evidence from research in mice suggests that combined exposure to prenatal inflammation and postnatal psychological stress in adolescence is associated with behavioral and neurochemical abnormalities consistent with those seen in neuropsychiatric disorders, highlighting the possibility of synergistic environment factors in the development of psychopathology (Giovanoli et al, 2013, 2014). A recent study in humans provides similar support, finding joint effects of exposure to prenatal infection and offspring psychological trauma in the development of schizophrenia (Debost et al, 2017). Such findings imply that prenatal exposure to maternal environmental factors, such as prenatal stress and infection, may influence fetal growth and development, resulting in long-term health consequences for offspring.…”

Maternal immune activation: Implications for neuropsychiatric disorders

“…Moreover, there is currently not an effective way to identify the at-risk pregnancies. The majority of pregnancies even at high risk will lead to healthy offspring and the resulting CNS disorders in offspring often do not appear for many years after birth and appear to be influenced by postnatal risk factors that synergize with genetic and prenatal risk to act as “second hits”(3, 13–15). Clearly, there is a compelling need for long-term and large prospective studies to identify the specific aspects of infection during pregnancy (the type of pathogen, extent of fever, timing of infection, etc.…”

Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: New insights for the key role of miR-125b-1-3p in neurodevelopmental processes

“…We have initially identified a specific miRNAs signature associated with stress exposure in different species and tissues, which were: i) peripheral blood of human controls exposed to childhood trauma as compared to controls who did not experience such stressful events; ii) hippocampus of PNS rats as compared with non- (Abbott et al, 2018;Malarbi et al, 2017) and suggest that stressful experiences, especially early in life, can affect neurodevelopmental and inflammatory-related systems, rendering stressed individuals more vulnerable to a further second stressful challenge (Debost et al, 2017;Giovanoli et al, 2013) and thus more vulnerable to develop a stress-related psychiatric disorder. Moreover, in our recent paper, we have demonstrated that FoxO1 is a novel potential candidate gene able to mediate the effect of stress early in life on the future vulnerability of developing a psychopathology (Cattaneo et al, 2018).…”