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Upon completion of the chapter, the reader will be able to:

  1. Recognize signs and symptoms of schizophrenia and be able to distinguish among positive, negative, and cognitive impairments associated with the illness.

  2. Explain pathophysiologic mechanisms that are thought to underlie schizophrenia.

  3. Identify treatment goals for a patient with schizophrenia.

  4. Recommend appropriate antipsychotic medications based on patient-specific data.

  5. Compare side-effect profiles of individual antipsychotics.

  6. Educate patients and families about schizophrenia, treatments, and the importance of adherence to antipsychotic treatment.

  7. Describe components of a monitoring plan to assess the effectiveness and safety of antipsychotic medications.


In most cases, schizophrenia is a devastating, chronically debilitating disorder. It may be thought of as a clinical syndrome, with many possible pathophysiological pathways that ultimately manifests with psychotic symptoms, including hallucinations, delusions, and disordered thinking. Commonly, these symptoms are accompanied by cognitive impairment (abnormalities in thinking, reasoning, attention, memory, and perception), impaired insight and judgment, and negative symptoms including loss of motivation (avolition), loss of emotional range (restricted affect), and a decrease in spontaneous speech (poverty of speech). Cognitive impairments and negative symptoms account for much of the poor social and functional outcomes. Schizophrenia is the fourth leading cause of disability among adults and is associated with substantially lower rates of employment, marriage, and independent living compared with population norms. However, earlier diagnosis, treatment, and advances in research and newer treatment developments have led to better outcomes.


Approximately 1% of the world population suffers from schizophrenia, with symptoms typically presenting in late adolescence or early adulthood.1 Prevalence is equal in men and women, but symptoms appear earlier in men with first hospitalization typically occurring at 15 to 24 years compared to 25 to 34 years.

The etiology of schizophrenia remains unknown. A genetic basis is supported by the fact that first-degree relatives of patients with schizophrenia carry a 10% risk of developing the disorder, and when both parents have the diagnosis, the risk to their offspring is 40%. For monozygotic twins, the concordance rate is about 50%. Many genes have been weakly associated with the development of schizophrenia; however, there is probably no single “schizophrenia gene.” Research continues to explore candidate genes, loci, and copy number variants, hoping to better understand the genetic contribution.2 Possibly, when a genetic liability is present, environmental stimuli may trigger expression of the illness. Some data suggest intrauterine exposure to significant stress, viral or bacterial infections may be a risk factor; however, more research is needed.


The dopamine hypothesis, the oldest pathophysiologic theory, proposes that psychosis is caused by excessive dopamine in the brain. This hypothesis followed the discovery that chlorpromazine, the first antipsychotic medication, was a postsynaptic dopamine antagonist. Drugs that ...

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