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Vol. 24, Art. 94 (pp. 1398-1417)    |    2024       

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Neuro-inflammatory theory of schizophrenia. Role of external factors (Literature review)

Khalchitsky S.E.1, Ivanov M.V.2, Stanovaya V.V.2, Khutoryanskaya Yu.V.3, Buslov K.G.1, Gracheva Yu.A.1, Komov Yu.V.3, Batotsyrenova E.G.3, Shchepetkova K.М.3, Kashuro V.A.3,4,5, Vissarionov S.V.1

1H.Turner National Medical Research Center for Children's Orthopedics and Trauma Surgery, Saint-Petersburg, Russia
2V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Saint-Petersburg, Russia
3St. Petersburg State Pediatric Medical University, St. Petersburg, Russia
4Herzen State Pedagogical University of Russia, Saint Petersburg, Russia
5 Research Institute of Hygiene, Occupational Pathology and Human Ecology at FMBA of Russia

Brief summary

Schizophrenia (SCZ) is a disorder with a heterogeneous etiology, involving a complex interaction between genetic and environmental risk factors. The immune system is now known to play a vital role in the function and pathology of the nervous system by regulating neuronal and glial development, synaptic plasticity, and behavior. The article examines environmental factors that influence the onset of schizophrenia, including exposure to pollution, gut dysbiosis, maternal immune activation, and early life stress, and how the effects of these risk factors relate to microglial function and dysfunction. Although the mechanisms involved in the pathogenesis of SCZ are still unclear, exposure to air pollution has been found to increase the expression of multiple inflammatory genes in humans and animal models. Taken together, the inflammatory state caused by exposure to air pollution has been shown to alter microglial function and neuronal development. as well as axonal myelination, thereby influencing several neurodevelopmental processes that have been implicated in the pathogenesis of SCZ. Of the immune genes that are associated with SCZ, many were also altered in either humans or animals exposed to pollutants, suggesting a genetic relationship between changes in pollution-induced signaling and SCZ. Microbiota influences complex behaviors such as social behavior, depression, anxiety, which is directly related to SCZ and other neuropsychiatric disorders. Recent studies support the causative role of the microbiota in neuropsychiatric disorders and highlight the role of the immune system in brain-gut communication in pathological conditions. The gut microbiome can influence the integrity of the blood-brain barrier (BBB), which contributes to increased neuroinflammation. The presence of intestinal microflora is necessary for the proper formation of the BBB in the early stages of development. The microbiome determines several risk factors for SCZ, including stress responses, promoting immune system activation and BBB disruption. Exposure to psychological stress or traumatic life events during the prenatal period, childhood, or adolescence leads to an increased risk of SCZ. Particularly during critical periods of development, certain stressors, such as physical or psychological abuse, socioeconomic disadvantage, living in an urban environment, and neglect, increase the risk of SCZ.


Key words

schizophrenia, neuroinflammation, microglia, environment, risk factors, neurogenesis.

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