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Familial Aggregation of Psychotic Symptoms in Huntington’s Disease

OBJECTIVE: The mutation responsible for Huntington’s disease is an elongated and unstable trinucleotide (CAG) repeat on the short arm of chromosome 4. Psychotic symptoms are more common in patients with Huntington’s disease than in the general population. This study explored the relationship of psychosis in Huntington’s disease patients with the number of CAG repeats and family history of psychosis. METHOD: Forty-four patients with Huntington’s disease, 22 with and 22 without psychotic symptoms, were recruited from two university-affiliated medical genetics clinics in Seattle and Vancouver, B.C. Psychiatric assessments of the subjects were made through chart review, and diagnoses were validated by structured interviews in a subset of patients. The demographic and clinical characteristics of the psychotic and nonpsychotic patients were compared. RESULTS: The two groups did not differ in demographic and clinical characteristics, except that subjects with psychosis were significantly more likely than nonpsychotic subjects to have a first-degree relative with psychosis. In eight of nine families in which Huntington’s disease probands with psychosis had a first-degree relative with psychosis, the relative’s psychosis co-occurred with Huntington’s disease. In the Huntington’s disease probands with psychosis, the onset of psychosis correlated with the onset of the neurological symptoms of Huntington’s disease, and the age at onset of psychosis was lower in probands with a higher number of CAG repeats. CONCLUSIONS: Patients with Huntington’s disease and psychotic symptoms may have a familial predisposition to develop psychosis. This finding suggests that other genetic factors may influence susceptibility to a particular phenotype precipitated by CAG expansion in the Huntington’s disease gene.

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