Maternal Immune Activation and Schizophrenia–Evidence for an Immune Priming Disorder

Abstract

Schizophrenia is a complex neurodevelopmental disorder affecting around 19. 8 million people worldwide. The etiology of the disorder is due to many interacting genetic and environmental factors, with no one element causing the full spectrum of disease symptoms. Amongst these factors, maternal immune activation (MIA) acting during specific gestational timings has been implicated in increasing schizophrenia risk in offspring. Epidemiological studies have provided the rationale for this link with prevalence of maternal infection correlating to increased risk, but these studies have been unable to prove causality due to lack of control of confounding factors like genetic susceptibility and inability to identify specific cellular and molecular mechanisms. Animal models have proved significantly more useful in establishing the extent to which MIA can predispose an individual to schizophrenia, displaying how maternal infection alone can directly result in behavioral abnormalities in rodent offspring. Alongside information from genome wide association studies (GWAS), animal models have been able to identify the role of complement proteins, particularly C4, and display how alterations in this system can cause development of schizophrenia-associated neuropathology and behavior. This article will review the current literature in order to assess whether schizophrenia can, therefore, be viewed as an immune priming disorder.

Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

“…This may trigger the fetal inflammatory response syndrome (FIRS) and results in an increased cytokine level of IL-1, IL-6, IL-8, and TNF-α, which has reported an increased risk of fetal developmental abnormalities ( Gotsch et al, 2007 ). Moreover, human studies have also demonstrated a significant correlation between MIA, FIRs and the development of neurodevelopmental psychiatric disorders such as ASD, schizophrenia, neurosensorial deficits, ADHD, and psychosis in early as well as in the later period of adulthood ( Knuesel et al, 2014 ; Brown and Conway, 2019 ; Choudhury and Lennox, 2021 ).…”

Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

“…Although the study of Karl A. Menninger and later on the work of Torrey and Peterson were pioneering in revealing the association between viral infection and subsequent psychotic disease [6,7], it was Mednick et al (1988) who showed that maternal influenza enhances the incidence of schizophrenia in the offspring [8]. Thenceforth, similar findings have been observed with other viral (e.g., cytomegalovirus, herpes simplex virus type 2, varicella-zoster and polio), bacterial (e.g., sinusitis, tonsillitis, pneumonia, and pyelonephritis), and parasite (e.g., toxoplasmosis) infections [9,10]. In the same line, other studies have connected rubella and cytomegalovirus infection during pregnancy with increased risk of ASD in the offspring [11,12], whereas cerebral palsy in adulthood associates with maternal infections [13,14].…”

Schizophrenia Hypothesis: Autonomic Nervous System Dysregulation of Fetal and Adult Immune Tolerance

“…Prenatal insults such as maternal immune activation (MIA) and prenatal iron deficiency have been linked to schizophrenia in offspring (Canetta and Brown, 2012;Aguilar-Valles et al, 2020;Choudhury and Lennox, 2021). MIA occurs when maternal inflammation during pregnancy raises inflammatory markers to above the normal range.…”