Abstract

Failures to replicate results in psychiatric genetics might be due to our inability to define the heritable phenotype. Instead of relying entirely on classical nosographical approaches, the use of a candidate symptom approach to identify more homogeneous forms of diseases among affected subjects and subclinical traits among first-degree relatives may increase genetic validity. Anhedonia may be a marker for subjects at risk of schizophrenia or schizophrenia spectrum disorders. We compared the familiality of anhedonia characterized by a high level of physical anhedonia (score above 23) in a sample of schizophrenic probands ( N=80) and their relatives ( N=78), with that in bipolar patients ( N=109), their relatives ( N=33) and normal controls ( N=94). We identified a subform of schizophrenia characterized by highly anhedonic schizophrenic probands with a three-fold higher familial risk of schizophrenia and schizophrenic spectrum disorders. We also found that their first-degree relatives had a high level of anhedonia. An intrafamilial correlation analysis confirmed the familial nature of anhedonia. Our data suggest that anhedonia is a candidate symptom for schizophrenia. Refining phenotype definition by studying subgroups of anhedonic and non-anhedonic probands with relevant candidate genes might be fruitful.

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