The cytokine hypothesis: A neurodevelopmental explanation for the emergence of schizophrenia later in life

Abstract

There is increasing evidence for the cytokine hypothesis,\rwhich states that exposure to elevated cytokines in utero due to maternal\rimmune activation is a major risk factor for the development of schizophrenia\rlater in life. This is supported by numerous epidemicologic studies that\rconnect multiple infections with schizophrenia emergence. Furthermore, cytokines\rare critically involved in early neurodevelopment and deviations from the norm\rcan result in abnormal neuroanatomy and brain chemistry. Animal models of\rschizophrenia also support the critical role of developmental neuroinflammation\rin predisposing the brain to anatomical and behavioral abnormalities. Although\rthere is strong evidence for the critical role of cytokines, they most likely\rwork with other contributing risk factors such as genetic predisposition. New\revidence indicates that cytokine exposure in utero may prime the brain and that\ra second stressor during adolescence, referred to as a second hit, may activate\rexisting developmental vulnerabilities resulting in the emergence of clinical\rschizophrenia. Further knowledge of these pathogenic processes and risk factors\rcould be very instrumental in reducing risk and slowing emergence of\rschizophrenia.