Prenatal Inflammation, Infections and Mental Disorders

Abstract

Background: The objective of this descriptive review is to summarize the current scientific evidence on the effect of prenatal exposure to maternal infection and immune response on the offspring's risk for mental disorders (schizophrenia spectrum disorders, autism spectrum disorders, attention-deficit hyperactivity disorder, anorexia nervosa, and mood disorders). Sampling and Methods: Studies were searched from PubMed and Ovid MEDLINE (R) databases with the following keywords: ‘prenatal exposure delayed effects' and ‘infection', and ‘inflammation' and ‘mental disorders'. A comprehensive manual search, including a search from the reference list of included articles, was also performed. Results: Prenatal exposure to maternal influenza appears to increase the offspring's risk for schizophrenia spectrum disorders, although studies are not fully consistent. Prenatal exposure to maternal fever and elevated cytokine levels seems to be related to the elevated risk for autism spectrum disorders in the offspring. No replicated findings of an association between prenatal infectious exposure and other mental disorders exist. Conclusions: Evidence for the effect of prenatal exposure to maternal infection on risk for mental disorders exists for several different infections, suggesting that common factors occurring in infections (e.g. elevated cytokine levels and fever), rather than the infectious agent itself, might be the underlying factor in increasing the risk for mental disorders. Additionally, it is likely that genetic liability to these disorders operates in conjunction with the exposure. Therefore, genetically sensitive study designs are needed in future studies.

Maternal infection requiring hospitalization during pregnancy and attention‐deficit hyperactivity disorder in offspring: a quasi‐experimental family‐based study

“…For instance, in urinary tract infections, bacteria/virus could directly reach the fetus or the baby when descending the vaginal canal. On the other hand, epidemiological studies support the association between prenatal exposure to various infectious pathogens and psychiatric disorders, suggesting that general immune activation (e.g., elevated cytokine levels) rather than the type of pathogen may be a common underlying pathway increasing the risk for mental disorders (Flinkkilä, Keski‐Rahkonen, Marttunen, & Raevuori, ; Scola & Duong, ).…”

Models of Intrauterine growth restriction and fetal programming in rabbits

“…Exaggerated maternal inflammation during pregnancy is usually associated with poor trophoblastic invasion, placental malperfusion and IUGR (Anton, Brown, Parry, & Elovitz, ; Robb, Cotechini, Allaire, Sperou, & Graham, ). It is also linked to neurodevelopmental disorders in the child (Angelidou et al, ; Brown, ; Flinkkilä, Keski‐Rahkonen, Marttunen, & Raevuori, ). Lipopolysaccharide (LPS) is an endotoxin that triggers systemic and local inflammatory response (Cotechini et al, ).…”

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

“…A connection between schizophrenia and inflammation is emerging in the literature, supported by many research approaches. 1,2 Research also supports the idea that individual risk for schizophrenia is increased with prenatal infection exposure, 3 and that a genetic contribution may also increase vulnerability to prenatal infection. 4 Imaging studies have found increased microglia activation binding in people with schizophrenia, [5][6][7] and genome-wide association studies have linked schizophrenia to the major histocompatibility locus.…”