Schizophrenia is associated with an increased frequency of tu-berculosis (not accounted for by institutionalization), celiac disease, myxedema and arteriosclerotic heart disease. Patients who present with atypical psychoses have been noted to have an increased risk of ankylosing spondylitis and uroarthritis, which may indicate a relationship between the histocompatibility com-plex and schizophrenia. Along these lines, there is a strikingly decreased risk for rheumatoid arthritis among patients with schizophrenia.
The cause of schizophrenia is currently not known. A leading view is that schizophrenia may be heterogeneous with respect to etiology. Thus, multiple causative mechanisms may give rise to distinct disease subtypes. If this is true, it is important for psy-chiatric researchers to differentiate the homogeneous subtypes of this illness. Moreover, it has been proposed that more than one causative mechanism might interact (the so-called double-hit hy-pothesis) to cause the illness in some individuals. In this section, the main etiological theories of schizophrenia are examined.
Schizophrenia represents a daunting challenge for genetic researchers for several reasons: the paucity of extendedmultigenerational family histories containing large numbers of affected individuals; the possibility of genetic heterogeneity, such as more than one phenotype or more than one genetic vari-ant; and a lack of agreement on the mode of transmission. The fo-cus of research has shifted to multiple genes of small to moderate effects which may compound their effects through interactions with each other and with other nongenetic risk factors.