Maternal Immune Activation and Autism Spectrum Disorder: Interleukin-6 Signaling as a Key Mechanistic Pathway

Abstract

An emerging area of research in autism spectrum disorder (ASD) is the role of prenatal exposure to inflammatory mediators during critical developmental periods. Epidemiological data has highlighted this relationship showing significant correlations between prenatal exposure to pathogens, including influenza, and the occurrence of ASD. Although there has not been a definitive molecular mechanism established, researchers have begun to investigate this relationship as animal models of maternal infection have support- ed epidemiological findings. Several groups utilizing these animal models have found that activation of the maternal immune system, termed maternal immune activation (MIA), and more specifically the exposure of the developing fetus to maternal cytokines precipitate the neurological, immunological and behavioral abnormalities observed in the offspring of these animals. These abnormalities have correlated with clinical findings of immune dysregulation, neurological and behavioral abnormalities in some autistic individuals. Additionally, researchers have observed genetic variations in these models in genes which regulate neurological and immunological development, similar to what is observed clinically in ASD. Altogether, the role of MIA and cytokine dysregulation, as a key mediator in the neuropathological, behavioral and possibly genetic irregularities observed clinically in autism are important factors that warrant further investigation.

Comorbidity of Physical and Mental Disorders in the Neurodevelopmental Genomics Cohort Study

“…44 In the current study, the robust association between immunologic/inflammatory conditions and mood disorders in youth demonstrates the importance of evaluation of immunologic/ inflammatory systems as a possible pathway to depression. Indeed, these findings confirm growing evidence from population-based samples that have demonstrated prospective links b aORs based on logistic regression models simultaneously controlling for gender, age, race/ethnicity, maternal education, and other physical disorders shown in the table (not adjusted for mental disorders).…”

Comorbidity of Physical and Mental Disorders in the Neurodevelopmental Genomics Cohort Study

“…44 In the current study, the robust association between immunologic/inflammatory conditions and mood disorders in youth demonstrates the importance of evaluation of immunologic/ inflammatory systems as a possible pathway to depression. Indeed, these findings confirm growing evidence from population-based samples that have demonstrated prospective links Diagnosis algorithms for DSM-IV indices of mental disorders considered endorsement of screen question, symptom count, duration, distress, and impairment.…”

Immune Privilege Revisited: The Roles of Neuronal MHC Class I Molecules in Brain Development and Plasticity

“…Current research efforts are focused on elucidating the consequences of prenatal immune insult on the brain development, so called "maternal immune activation". Both schizophrenia and autism have been genetically linked to MHC cluster and to prenatal immune insult (Soumiya et al 2011, Buehler 2011, Escobar et al 2011, Patterson 2011, Fatemi et al 2011, Parker-Athill and Tan 2010, Boksa 2010, Currenti 2010, Li et al 2009, Patterson 2009, Smith et al 2007, Cohly and Panja 2005, Patterson 2002, Stubbs and Magenis 1980. Future studies will no doubt elucidate the interactions between the nervous and immune systems in more detail, as well as shed more light on the vast polymorphism of MHC class I molecules, especially in the light of their neuronal functions.…”