Psychiatric disorders in 36 families with Wolfram syndrome

Abstract

Objective: The purpose of this study was to test the hypothesis that heterozygous carriers of the gene for the Wolfram syndrome, who constitute about 1% of the population, are predisposed to significant psychiatric illness. The Wolfram syndrome is an autosomal recessive neurodegenerative syndrome in which 25% of the individuals who are homozygous for the condition have severe psychiatric symptoms that lead to suicide attempts or psychiatric hospitalizations.

Method: The authors collected questionnaires, death certificates, and hospital records for blood relatives and their spouses in 36 families of individuals with the Wolfram syndrome and compared the proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness to the proportion of spouses with the same manifestations.

Results: The proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness significantly exceeded the proportion of spouses with the same manifestations.

Conclusions: Since heterozygous carriers of the gene for the Wolfram syndrome are 50-fold more common among the blood relatives than among the spouses, the larger proportion among blood relatives is evidence that heterozygous carriers of the gene for the Wolfram syndrome are predisposed to significant psychiatric illness.