Cytokines and the neurodevelopmental basis of mental illness

Abstract

Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioral and neurological abnormalities.

The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis

“…Moreover, we also evaluated the activity of glucocorticoids as key molecules in the process of stress that may act during this period. Although glucocorticoids are essential for normal brain development, exposure of the fetal brain to an excess of glucocorticoids can also modify fetal brain development and permanently alter the function of the hypothalamic pituitary adrenal axis (HPA) in postnatal life [23][24][25]. There is evidence suggesting that events during prenatal life have longlasting effects during postnatal development and in the adult, for example altering the regulation of the HPA, increasing blood pressure and/or impairing glucose tolerance in the brain [26].…”

A perspective on the developmental toxicity of inhaled nanoparticles

“…If this is indeed the case, it could be argued that the observation of release of inflammatory mediators in acute and sub-acute inhalation studies in the first tier would trigger repeated dose toxicity studies that investigate the effects of nanomaterial exposure on reproductive organs and the developing fetus. This is all the more relevant, as both reproductive function and fetal development is indeed sensitive to oxidative stress and inflammation [8,12,13,82,83].…”

“…If this developmental programming does not match the conditions in postnatal life, physiological dysregulation may arise and affect health later in life [80]. Taking into account that low grade chronic inflammation is a leading mechanism of several disorders in adult humans [81], it might not be surprising that maternal inflammation (along with oxidative stress) may interfere with fetal development and alter organ function in the offspring later in life [8,12,13,[82][83][84]. This could be viewed as an aspect of fetal adaptation to the inflammatory environment of the mother.…”

“…Many particles elicit inflammation and oxidative stress in the lungs [9][10][11]. Specifically, during pregnancy, inflammation and oxidative stress induce perturbations that have been shown to have detrimental and longlasting consequences for fetal development [12,13]. Furthermore, inflammatory mediators are biologically active molecules that may trigger a range of responses in the tissues they reach.…”

Rethinking Schizophrenia in the Context of the Person and Their Circumstances: Seven Reasons

“…Many studies have demonstrated high levels of cytokines and other signs of immune system activation. Furthermore, cytokines are critically involved in early neurodevelopment and deviations from the norm can result in abnormal neuroanatomy and brain chemistry (Howard, 2013; Ratnayake et al, 2013). …”