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