Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited.

OBJECTIVE To highlight emerging evidence for clinical and biological links between autism/pervasive developmental disorder (PDD) and schizophrenia, with particular attention to childhood-onset schizophrenia (COS). METHOD Clinical, demographic, and brain developmental data from the National Institute of Mental Health (and other) COS studies and selected family, imaging, and genetic data from studies of autism, PDD, and schizophrenia were reviewed. RESULTS In the two large studies that have examined this systematically, COS is preceded by and comorbid with PDD in 30% to 50% of cases. Epidemiological and family studies find association between the disorders. Both disorders have evidence of accelerated trajectories of anatomic brain development at ages near disorder onset. A growing number of risk genes and/or rare small chromosomal variants (microdeletions or duplications) are shared by schizophrenia and autism. CONCLUSIONS Biological risk does not closely follow DSM phenotypes, and core neurobiological processes are likely common for subsets of these two heterogeneous clinical groups. Long-term prospective follow-up of autistic populations and greater diagnostic distinction between schizophrenia spectrum and autism spectrum disorders in adult relatives are needed.