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Twin Studies

Twin studies tend to be relatively small, given the difficulty in recruiting cases and the related arguments concerning their power can be made. In fact, the early, canonical twin study of Slater and Shields²¹ found that nearly as many of the co-twins of schizophrenic probands had affective disorder as had schizophrenia and that there were actually more parents with affective disorder than with schizophrenia. However, this, like other departures from the Kraepelinian model, was attributed to misdiagnosis.²² There have been few subsequent attempts to explore or challenge diagnostic boundaries using twin studies. An exception was the study by Farmer et al,²³ who showed in a study of the first half of the Maudsley twin series that affective disorders, particularly those with mood-incongruent psychotic features, are genetically related to schizophrenia.

More recently, Cardno et al²⁴ reasoned that overlap in genetic risk factors between schizophrenia and bipolar disorder might have been obscured in twin studies of psychosis because of the adoption of a hierarchical rule that requires that each individual be given a single lifetime diagnosis. Because schizophrenia was placed higher in terms of severity and “organicity,” schizophrenic symptoms tended to “trump” those of mood disorder. When Cardno et al²⁴ defined syndromes nonhierarchically, they demonstrated a clear overlap in genetic liability between syndromically defined mania and schizophrenia.²⁴ Their model fitting suggested that, whereas some susceptibility genes are specific to schizophrenia and some to bipolar disorder, there is a third group of genes, influencing across the board susceptibility to schizoaffective disorder, schizophrenia, and bipolar disorder. A graphic illustration of the varied expression of the same set of susceptibility genes is provided by the Maudsley triplets—a set of genetically identical triplets, 2 of whom had a lifetime diagnosis of schizophrenia and the third a lifetime diagnosis of bipolar disorder.²⁵

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