Familial aggregation of psychotic symptoms in Huntington's disease

Objective: The mutation responsible for Huntington's disease is an elongate d and unstable trinucleotide (CAG) repeat on the short arm of chromosome 4. Psychotic symptoms are more common in patients with Huntington's disease t han in the general population. This study explored the relationship of psyc hosis in Huntington's disease patients with the number of CAG repeats and f amily history of psychosis. Method: Forty-four patients with Huntington's disease, 22 with and 22 witho ut psychotic symptoms, were recruited from two university-affiliated medica l genetics clinics in Seattle and Vancouver, B.C. Psychiatric assessments o f the subjects were made through chart review, and diagnoses were validated by structured interviews in a subset of patients. The demographic and clin ical characteristics of the psychotic and nonpsychotic patients were compar ed. Results: The two groups did not differ in demographic acid clinical charact eristics, except that subjects with psychosis were significantly more likel y than non psychotic subjects to have a first-degree relative with psychosi s. in eight of nine families in which Huntington's disease probands with ps ychosis had a first-degree relative with psychosis, the relative's psychosi s co-occurred with Huntington's disease. In the Huntington's disease proban ds with psychosis, the onset of psychosis correlated with the onset of the neurological symptoms of Huntington's disease, and the age at onset of psyc hosis was lower in pro bands with a higher number of CAG repeats. Conclusions: Patients with Huntington's disease and psychotic symptoms may have a familiar predisposition to develop psychosis. This finding suggests that other genetic factors may influence susceptibility to a particular phe notype precipitated by CAG expansion in the Huntington's disease gene.