Behavioral markers of schizophrenia useful for genetic studies

The advent of powerful molecular biological techniques have already led to the discovery of chromosomal loci linked to some genetically transmitted diseases. These techniques, however, lose their power if applied to a disease trait that is not Mendelian in its transmission. The low familial prevalence of psychiatric diseases such as schizophrenia make these techniques unsuitable for linkage studies of these conditions, if identification of schizophrenia relies solely on the clinical manifestation of the schizophrenic psychosis. Broadening the disease phenotype in diseases such as schizophrenia, with low recurrence risk, and narrowing it in diseases such as major affective disorder, with very high recurrence risk, may be an effective strategy for linkage studies of these diseases. Several alternative phenotypes are discussed, including smooth pursuit eye movement abnormalities, event related potentials, and deficient attentional deployment as measured by the continuous performance test. The strategy assumes that schizophrenia is a pleiotropic disorder, and that the psychosis is the rare form of the condition. The paper focuses principally on smooth pursuit eye movement abnormalities, and claims a plausible place for them as an independent expression of schizophrenia. With this strategy, the possibility for successful linkage studies increases, since familial distributions of schizophrenia and pursuit abnormalities, considered together, appear to fit an autosomal dominant pattern.