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Schizophrenia is a psychiatric illness that can be profoundly disabling and is usually chronic in nature. The cause is not known, but there appears to be a genetic predisposition. The etiology has been conceptualized in a stress/diathesis (vulnerability) model: Biological and environmental factors (e.g., drug abuse, psychosocial stresses) interact with a genetic vulnerability to precipitate the illness. Several theories have been proposed to explain the observed biological abnormalities of the disorder, including over-activity of the dopamine neurotransmitter systems in the central nervous system, changes in brain structure (e.g., enlargement of the lateral cerebral ventricles) and brain function (e.g., decreased frontal lobe function [hypofrontality], as evidenced by diminished blood flow, and deficits in attention and sensory filtering). Psychological and social factors are considered important in the expression and course of the disorder. It is likely that schizophrenia constitutes a group of disorders rather than a single entity; these disorders present with similar clinical signs and symptoms, but the etiologies, treatment responsiveness, and course of illness in each vary.

Detailed descriptions of the illness date back to the nineteenth century. Emil Kraepelin (1856-1926) used the term dementia praecox to describe psychiatric states with an early onset and deteriorating course. Eugen Bleuler (1857-1939) coined the term schizophrenia for a "splitting of the mind," in his belief that the illness was a result of the disharmony of psychological functions. The diagnosis of schizophrenia requires observation and clinical interviewing. No sign or symptom is specific for the illness, nor do any laboratory tests exist to establish the diagnosis. The DIAGNOSTIC AND STATISTICAL MANUAL for Mental Disorders-3rd edition contains the diagnostic guidelines of the American Psychiatric Association for schizophrenia. These include: the presence of characteristic psychotic symptoms (delusions, HALLUCINATIONS, a thought disorder, inappropriate emotion); impaired work, social functioning, and selfcare; and continuous signs of the illness for at least six months. The symptoms of an affected individual can change with time, therefore longitudinal follow-up is important. It should be noted that certain of these symptoms can be indicative of other conditions (including drug abuse [cocaine, crack, PCB, amphetamines], head injury, brain tumors, as well as other psychiatric disorders). Furthermore, it is important to take into account the educational level, intellectual ability, and cultural affiliation of the individual when making a diagnosis. The onset of illness is usually in late adolescence or early adulthood and is generally insidious. The typical course of schizophrenia is characterized by exacerbations and remissions. A gradual deterioration in functioning generally occurs that eventually reaches a plateau. However, a small proportion of persons may recover. It is estimated that 20 percent to 30 percent of affected individuals can lead somewhat normal lives whereas another 20 to 30 percent continue to experience moderate symptoms.

The prevalence rates of schizophrenia vary to a limited degree worldwide, but in the United States the lifetime prevalence is estimated to be 1 percent (about one in one-hundred people). In industrialized countries, there is a disproportionate number of schizophrenic patients in the lower socioeconomic classes. Some experts feel this is due to the schizophrenic's loss of education and social opportunity, while others feel this is more a direct result of the stresses of poverty.

The management of affected individuals involves hospitalization when there is an exacerbation of the illness, plus the use of medication. The mainstay of pharmacologic treatment is the class of drugs known as ANTIPSYCHOTICS. Many antipsychotics are available and they act to control the psychotic symptoms; most of them do so by blocking the actions of the neurotransmitter, dopamine. About 75 percent of patients respond to these drugs; however, there are side effects, including muscle stiffness, tremors, and weight gain. The drugs may also cause tardive dyskinesia (TD), a disorder that causes involuntary, repetitive movements of the body, mouth, and tongue.

Some of the more commonly prescribed antipsychotics include: chlorpromazine, fluphenazine, haloperidol, olanzapine, and risperidone. The atypical antipsychotic, clozapine, has been identified as the best choice for managing resistant schizophrenia; however, up to 73 percent of patients treated with clozapine report clinically relevant side effects. These can be quite severe, and include potentially fatal neuroleptic malignant syndrome (NMS), myocarditis, cardiomyopathy, and dangerous lowering of white blood cell count (for the latter, regular and frequent blood testing is required during the treatment period). In a study following 8,000 patients in Australia who started clozapine treatment between January 1993 and March 1999, fifteen developed myocarditis, and eight developed cardiomyopathy; a total of six patients died within the six years.

After a person has recovered from an acute episode of schizophrenia, the emphasis is on practical aspects of management: living arrangements, self-care, employment, and social relationships. Education of and support made available to family members are important and can have an impact on relapse rates in the patient. Many schizophrenic patients have to remain on antipsychotic medication for prolonged periods, since the rate of relapse is high after drug discontinuation. Side effects, primarily of a neurologic nature (e.g., TD), are a source of concern, but in most cases the benefits of symptom control outweigh the risks of pharmacotherapy. Making sure that the patient complies with medication use is often a problem.