The Impact of Systemic Inflammation on Neurodevelopment

Abstract

Inflammatory mediators affect the brain during development. Neurodevelopmental disorders such as autism spectrum disorders, cognitive impairment, cerebral palsy, epilepsy, and schizophrenia have been linked to early life inflammation. Recent advances have shown the effects of systemic inflammation on children's neurodevelopment. We discuss the potential mechanisms by which inflammatory molecules can exert their effects on the developing brain and consider the roles of MHC class I molecules, the HPA axis, glial cells, and monoamine metabolism. Methods to prevent the effects of cytokine imbalance may lead to the development of new therapeutics for neuropsychiatric disorders. Future research should focus on identifying at-risk individuals and early effective interventions to prevent long-term neurodevelopmental disabilities.

Innate Immunity and Neuroinflammation in Neuropsychiatric Conditions Including Autism Spectrum Disorders: Role of Innate Immune Memory

“…In ASD patients, just like in other neuropsychiatric conditions, a role of inflammation has been long suspected, and more and more evidence has been accumulating [90][91][92]. In the research of innate immune abnormalities in ASD children, we have also found evidence of dysregulated innate immune responses, shifting to proinflammatory responses in a subset of ASD subjects [88,93,94].…”

Association between preeclampsia and autism spectrum disorder: a population‐based study

“…Thus, while uncomplicated pregnancies have a normal systemic inflammatory response (Redman, Sacks, & Sargent, 1999), preeclampsia results in a state of exaggerated maternal inflammation (Maher, McCarthy et al, 2018;Redman et al, 1999). Therefore, maternal inflammation, a recognised risk factor for poor neurodevelopmental outcome, could act as a mediator between preeclampsia and development of ASD, and the proinflammatory cytokine interleukin (IL)-6 may be a leading candidate in this regard (Jiang et al, 2018). Straughen et al (2017) demonstrated that placental inflammation of any type is associated with an increased likelihood of ASD, while circulating levels of maternal IL-6 have been shown to be inversely associated with brain connectivity and offspring cognition at 12 months of age, as well as short and long-term influences in offspring behaviour in separate studies (Rasmussen et al, 2018;Spann, Monk, Scheinost, & Peterson, 2018).…”

“…Such factors may include inflammatory cytokines given that preeclampsia is associated with chronic immune activation, leading to a significant increase in the circulation of proinflammatory cytokines. Therefore, maternal inflammation, a recognised risk factor for poor neurodevelopmental outcome, could act as a mediator between preeclampsia and development of ASD, and the proinflammatory cytokine interleukin (IL)-6 may be a leading candidate in this regard (Jiang et al, 2018). Therefore, maternal inflammation, a recognised risk factor for poor neurodevelopmental outcome, could act as a mediator between preeclampsia and development of ASD, and the proinflammatory cytokine interleukin (IL)-6 may be a leading candidate in this regard (Jiang et al, 2018).…”

“…The prevalence of ASD is approximately 1.5% (Idring et al, 2015;Lyall et al, 2017), and while genetics play a major role in the development of ASD, the environmental contribution is estimated to be between 17% and 50% (Sandin et al, 2014(Sandin et al, , 2017. This highlights the importance of investigating factors contributing to the likelihood of its onset and potentially facilitates the development of appropriate interventions (Jiang, Cowan, Moonah, & Petri, 2018). Furthermore, while often comorbid with intellectual disability, previous results indicate that risk factors for ASD with and without intellectual disability may differ and is, therefore, important to examine ASD according to the presence or absence of intellectual disability (Abel et al, 2013;Langridge et al, 2013).…”

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

“…Inflammatory activity drives levels of circulating pro-inflammatory cytokines, which fluctuate in response to acute insults, like infection or injury, and/or chronic disruptions in homeostasis and tissue function (Cohen et al, 2012;Gouin, Glaser, Malarkey, Beversdorf, & Kiecolt-Glaser, 2012;Hotamisligil, 2017;Scrivo, Vasile, Bartosiewicz, & Valesini, 2011). This gives inflammatory processes wide berth to impact brain structure, evidence of which is reflected in both early development and adulthood (Bettcher et al, 2013(Bettcher et al, , 2014Favrais et al, 2011;Jiang, Cowan, Moonah, & Petri Jr., 2018;Lim et al, 2013;Rasmussen et al, 2018) and in health and illness (Benedetti et al, 2016;Chiang et al, 2017;Najjar & Pearlman, 2015;Prasad et al, 2015;Yadav et al, 2010). Our study aimed to evaluate common genetic influences on white matter microstructure, as measured by DTI, and markers of inflammation, as measured by circulating proinflammatory cytokines in humans.…”