The case for heterogeneity in the etiology of schizophrenia.

To confirm etiological heterogeneity, it is required that schizophrenic patients may be separated into at least two classes having different known etiologies and, perhaps, different pathophysiological signatures. In contrast, the homogeneity hypothesis asserts that there is a single necessary and sufficient cause or configuration of causes of schizophrenia. Because the link between phenotypic heterogeneity and etiological heterogeneity is tenuous, attempts to use purely phenotypic data to infer etiologic heterogeneity must be viewed cautiously. We examined three candidate causes for schizophrenia: genes, obstetric complications and viral infection. Cytogenetic studies show that some rare cases of schizophrenia are due to gross abnormalities of chromosomes. As for the large majority of schizophrenic patients, the candidate cause data most certainly reject the most parsimonious version of the hypothesis of etiological homogeneity: that all schizophrenia is caused by exactly the same pattern of genetic mutations, birth related complications and exposure to the same viral infections. We conclude that the heterogeneity debate should consider the possibility of rewording the question: 'Heterogeneity: yes or no?' to 'Heterogeneity: how much?'