The Genetics of Childhood-Onset Schizophrenia: When Madness Strikes the Prepubescent

Stratification by age at onset has been useful for genetic studies across all of medicine. For the past 20 years, the National Institute of Mental Health has been systematically recruiting patients with onset of schizophrenia before age 13 years. Examination of familial transmission of known candidate risk genes was carried out, and a 10% rate of cytogenetic abnormalities was found. Most recently, high-density, array-based scans for submicroscopic rare copy number variations (CNVs) have suggested that this kind of genetic variation occurs more frequently than expected by chance in childhood-onset schizophrenia (COS) and at a higher rate than observed in adult-onset disorder. Several CNVs and cytogenetic abnormalities associated with COS are also seen in autism and mental retardation. Populations with COS may have more salient genetic influence than adult-onset cases. The relationship of rare CNVs to prepsychotic development is being studied further.