Problems and pitfalls of the family history positive and negative dichotomy: response to Dalén.

The authors defend the proposition that the simple division of schizophrenia into family history positive versus family history negative in the hope of uncovering etiological heterogeneity is too naive for a multifactorial disorder as contrasted with rare, mendelizing genetic conditions. Dalén is correct to forecast that a monolithic homogeneity view about the origins of schizophrenia is likely to be refuted and that it is important to pursue such a strategy. Using computed tomographic brain scan results and the simple dichotomy of family history positive versus family history negative as an illustration, we show the weakness (lack of statistical power) of the strategy. The problem arises from the fact that a negative family history for schizophrenia characterizes the vast majority of schizophrenic patients just as it does for insulin-dependent diabetes, another genetically influenced multifactorial disorder. A continuum from more genetic to less genetic variation in the etiology of schizophrenia fits the available familial patterns of risk.