A Turning Point in Schizophrenia Genetics

tially with degree of relation to an affected individual. Schizophrenia has been called “arguably the worst disFor example, compared with the z1% risk the general ease affecting mankind.” The worldwide lifetime prevapopulation has to develop schizophrenia, the risk to lence of the disorder is z1%. In 1990, the cost of caring first cousins of schizophrenics is z2%, the risk to their for patients with schizophrenia in the United States was siblings is z9%, and the risk to someone with both an estimated to be $33 billion, accounting for z2.5% of affected sibling and a parent is z16%. Second, twin total health care expenditures. The substantial funds studies comparing the concordance for schizophrenia being spent on the disease only reach a fraction of the in monozygotic (MZ) twin pairs (who, in principle, share affected population, since an estimated third to half of all of their genes) with the concordance in dizygotic (DZ) the homeless population, who never receive care, suffer twin pairs (who share half of their genes) demonstrated from schizophrenia. that theMZ concordance rate (46%–48%) is significantly In the absence of good biological markers, schizohigher than the DZ rate (4%–14%). Gottesman and phrenia is defined in terms of a clinical syndrome. Case Shields (1982) found a slightly higher (58%) concoridentification usually begins with the observation of psydance rate in a small number of MZ twin pairs who had chotic symptoms (delusions, hallucinations) and bizarre been brought up apart. Third, adoption studies comparbehavior, but many patients also have “negative” symping the prevalence of schizophrenia in biological relatoms, including low levels of emotional arousal, mental tives who have been separated by adoption early in life activity, and social drive. Long-standing impairment is and in adoptive, not genetically related relatives who observed in patients with schizophrenia. A number of shared the same environment demonstrated that prevarelatively precise operational definitions of the synlence of schizophrenia is higher in the biological than drome exist, such as those in the editions of the Diagin the adoptive relatives. nostic and Statistical Manual of Mental Disorders (DSM; Taken together, these observations suggest the presAmerican Psychiatric Association, 1987), which when ence of a strong genetic component in the susceptibility used in conjunction with standardized research interto schizophrenia. At the other end, probable environviews can lead to a reliable, valid, and “heritable” diagmental insults may include obstetric complications or nosis of the disease. birth traumas (McNeil, 1995), extreme nutritional defiThere is a mounting body of evidence from a series ciency of the mother during early gestation (Susser et of neuropathological and magnetic resonance imaging al., 1996), viral infections and autoimmune disorders (MRI) studies to support the view that schizophrenia can (Wright and Murray, 1996), and other unspecified envibe a consequence of disturbances in development of ronmental factors. the brain starting probably as early as during the intra-