Genetic approaches to polydipsia in schizophrenia: A preliminary report of a family study and an association study of an angiotensin‐converting enzyme gene polymorphism

The pathophysiology of polydipsia in patients with schizophrenia is inadequately understood. This study aims to investigate the genetic influence on polydipsia in schizophrenia, and is comprised of a family study and an association study. First, we screened in‐patients in 14 psychiatric hospitals and found a total of 36 pairs of a proband and his/her first‐degree relative, both of whom were diagnosed with schizophrenia. Among these pairs, a significant familial concordance of polydipsia was found (Fisher's exact test, two‐sided, P  = 0.0014; odds ratio, 88.20; 95% confidence interval, 7.31–1064.34). These results indicate that genetic factors may underlie the pathophysiology of polydipsia in patients with schizophrenia. Subsequently, we examined the genetic association between polydipsia/water intoxication and the angiotensin‐converting enzyme (ACE) insertion (I)/deletion (D) polymorphism in patients with chronic schizophrenia (polydipsics: n = 65; non‐polydipsics: n = 97) because several lines of evidence suggested that ACE might be involved in the development of polydipsia in schizophrenia. The D allele of ACE was found to be associated with a non‐significant trend toward an increased risk of polydipsia ( P  = 0.086). Furthermore, a significant allelic association was found between the D allele of ACE and water intoxication ( P  = 0.0392). This significance remained after the data were adjusted for confounding variables by regression analysis. These results suggest that the ACE D allele may be a risk factor for polydipsia/water intoxication in patients with schizophrenia. © 2003 Wiley‐Liss, Inc.