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Schizophrenia is one of our most important public health problems It is a common tragic and devastating mental illness that typically strikes young people just when they are maturing into adulthood Once it strikes morbidity is high 60 percent of patients are receiving disability benefits within the first year after onset 1 as is mortality the suicide rate is 10 percent 2 Despite the fact that people with schizophrenia are all around us the lifetime prevalence is 1 percent worldwide 2 this illness is often misunderstood and people with schizophrenia are stigmatized by both the medical profession and the public Our understanding of the causation of schizophrenia has increased in the past several decades Schizophrenia is a disease of the brain that is expressed clinically as a disease of the mind Both its symptoms and signs and its associated cognitive abnormalities are too diverse to permit its localization in a single region of the brain The working hypothesis shared by most investigators is that schizophrenia is a disease of neural connectivity caused by multiple factors that affect brain development 345 Our current model of the causation of schizophrenia is very similar to that used to understand cancer That is schizophrenia probably occurs as a consequence of multiple hits which include some combination of inherited genetic factors and external nongenetic factors that affect the regulation and expression of genes governing brain function or that injure the brain directly Some people may have a genetic predisposition that requires a convergence of additional factors to produce the expression of the disorder This convergence results in abnormalities in brain development and maturation a process that is ongoing during the first two decades of life 6 The abnormalities are typically not focal but rather involve distributed neural circuits and neurotransmitter systems When the connectivity and communication within neural circuitry are disrupted patients have a variety of symptoms and impairments in cognition Behind this diversity however is
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