Admixture analysis of age at onset in obsessive-compulsive disorder.

Background: 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.

Method: Admixture analysis was used to determine the best-fitting model for the observed AAO of 161 OCD patients.

Results: 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.

Conclusions: 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.