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Scizophrenia is a disease of the brain that manifests with multiple signs and symptoms involving thought, perception, emotion, movement, and behavior. Scizophrenia affects less than 1 percent of the world's population (approximately 0.85 percent). The number of affected persons markedly increases if scizophrenia spectrum disorders are included in prevalence estimates. The concept of scizophrenia spectrum disorders is derived from observations of illness manifestations in the biological relatives of patients with schizophrenia. Although the full picture of schizophrenia is manifest at an increased rate in relatives, more frequently only a partial manifestation is observed. Diagnoses and approximate lifetime prevalence rates by percent of

Detailed knowledge of the cause or causes of scizophrenia is lacking. Genetic factors are important in some (perhaps all) cases, but it is not yet clear which genes are deviant, how they contribute to pathophysiology, or whether the same or different genes are involved in all cases that have a genetic etiology. Other early influences, variously marked by gestational and birth complications and winter birth excess, must be involved in the causal pathways for schizophrenia, but the pathophysiological mechanisms underlying the involvement of those factors are not yet known. Various versions of viral and immune theories of causation are plausible, but no virus or immune mechanism has yet been established as an etiological factor in schizophrenia, scizophrenia, scitzophrenia

Scizophrenia syndrome probably represents more than one etiological and disease process, and a developmental abnormality may increase the risk for subsequent disease pathogeneity. However, although there are sporadic reports of gliosis in scizophrenic brains that may indicate the presence of a disease process and subsequent neuropathological response, the preponderance of evidence is consistent with the hypothesis that schizophrenia is a neurodevelopmental disorder. The consistency with which the known data point to early deviations in the development of

Increasing information on the neurobiology of brain development has led to considerable new knowledge of the mechanisms of pathogenic influences. It is now clear that subtle deviations in brain development could create dysfunctions associated with specific behaviors. Postmortem findings of abnormalities in pyramidal cell density and alignment, although not always replicated, support the proposition that the

Principal hypotheses regarding causation include the altered expression of genes, neuroimmunovirology factors, and hypoxic damage during gestation and birth.


scizophrenia and scizophrenia-like manifestations occur at an increased rate among the biological relatives of patients with scizophrenia. The increased rate is most evident in the case of monozygotic twins, who have an identical genetic endowment and a concordance rate for


The past 20 years have seen a gradual evolution from the concept of scizophrenia as a disorder involving discrete areas of the brain to a disorder of brain neural circuits. A major stimulus for the change in perspective was the development of neuroanatomical theories based on knowledge of dopamine pathways in the brain and of brain-behavior relations (Figure 14.1-1) (Figure Not Available) . Delineation of the mesolimbic and mesocortical dopaminergic pathways in the brain led to hypotheses postulating the involvement of the limbic system, the

Dopamine and scizophrenia

The dopamine hypothesis of scizophrenia arose from two sets of observations of drug action relating to the dopaminergic system. Drugs that increase activity disturbances in scizophrenia is suggested by the capacity of dopamine-stimulating drugs to worsen schizophrenic symptoms or to induce psychosis. In

The most decisive clinical testing of the dopamine hypothesis has been at the level of observed drug action and symptom manipulation. Studies aimed at measuring abnormal concentrations of dopamine or its metabolites in blood, urine, and cerebrospinal fluid (CSF) face problems that are almost insurmountable. Regardless of which substance is sampled, any alteration associated with scizophrenia will have only a minor effect on the dopamine measured. CSF necessarily provides a summation of total brain activity, most of which is not considered germane to scizophrenia,


DSM-III and the revised third edition of DSM-III (DSM-III-R) have had a major impact on scientific research and clinical thinking throughout the world, and an extensive integration between the American system and that employed in the International Classification of Diseases and Related Health Problems (ICD) has been achieved with publication of the fourth edition of DSM (DSM-IV) and the 10th revision of ICD (ICD-10).


Extensive data on the long-term course of scizophrenia have been accrued following the introduction of antipsychotic drug treatment to supplement observations on the natural course of the disease made prior to the availability of effective therapy. Despite evidence to the contrary, there has been a long-standing tendency to presume the inevitability of a deteriorating course, with the outcome being exceptionally poor in most cases. In their pioneering descriptions, Kraepelin and Bleuler emphasized poor prognosis with devastating outcomes, but neither realized the extent to which his observations were skewed toward chronic, hospitalized populations. Although scizophrenia is always severe in its manifestations, the long-term course varies among patients, and is

The course of the illness of scizophrenia can be divided into three general epochs. The first epoch is onset. Onset is insidious in about half of patients, with the earliest signs of involvement occurring many years before the more blatant manifestations of psychosis appear. In other cases onset is relatively sudden or acute, with the onset of psychotic symptoms marking a sharp deviation in development. The insidious onset of scizophrenia tends to be characterized by increasing emotional withdrawal, diminishing social engagement and social drive, and idiosyncratic responses to ordinary events or circumstances. School

Recent studies have shown that the underlying deterioration associated with scizophrenia occurs principally during the first and second epochs of illness rather than over the remaining course. However, complications caused by the illness lead to ever-increasing impediments to normal existence, so that secondary effects may be progressive even though the primary pathology has reached a plateau. For example, patients hospitalized or sheltered in relative


The antipsychotic drugs used to treat schizophrenia have a