Admixture analysis of age at onset in obsessive–compulsive disorder

Abstract

Age at onset (AAO) has been useful to explore the clinical, neurobiological and genetic heterogeneity of obsessive-compulsive disorder (OCD). However, none of the various thresholds of AAO used in previous studies have been validated, and it remains an unproven notion that AAO is a marker for different subtypes of OCD. If AAO is a clinical indicator of different biological subtypes, then subgroups based on distinct AAOs should have separate normal distributions as well as different clinical characteristics. Admixture analysis was used to determine the best-fitting model for the observed AAO of 161 OCD patients. The observed distribution of AAO in OCD is a mixture of two Gaussian distributions with mean ages of 11.1 +/- 4.1 and 23.5 +/- 11.1 years. The first distribution, defined by early-onset OCD, had increased frequency of Tourette's syndrome and increased family history of OCD. The second distribution, defined by late-onset OCD, showed elevated prevalence of general anxiety disorder and major depressive disorder. These results, based on a statistically validated AAO cut-off and those of previous studies on AAO in OCD, suggest that AAO is a crucial phenotypic characteristic in understanding the genetic basis of this disorder.