This K23 Award focuses on the psychopharmacology of pervasive developmental disorders (PDDs). Despite numerous treatment studies in autistic disorder (autism), research specifically focused on the diagnostic subtype of FDD not otherwise specified (NOS) is greatly lacking. In fact, there have been no published double-blind, placebo-controlled trials of any drug specific to this disorder. Moreover, recent epidemiological research has found that PDD NOS is the most common subtype of PDD. Therefore, it is critically important that pharmacologic research on PDDs other than autism be conducted. Often considered higher functioning, these children suffer from severe lifelong impairments in core social skills and frequently associated irritability. Symptoms of irritability, including aggression, tantrums, and self- injury, can be more serious than those seen in autism. The candidate's long-term objective is to determine the most effective and safe pharmacologic treatments for PDDs, specifically PDD NOS. Her aims for this K23 Award are: (1) to develop an in depth understanding of clinical research and psychopharmacology by conducting a treatment study in PDD NOS; and (2) to obtain a Master of Science in Clinical Research degree at Indiana University, focusing on courses including research ethics, biostatistics, and research methodology. She will work closely with her mentor, Christopher J. McDougle, M.D., an international expert in the pharmacotherapy of PDDs, to accomplish these aims and transition into her career as an independent investigator. This proposal is a double-blind, placebo-controlled and open-label continuation study of aripiprazole for irritability in 60 children and adolescents with PDD NOS. Pilot data from the applicant suggests that aripiprazole is effective for targeting symptoms of irritability commonly observed in PDD NOS, including aggression, tantrums, and self-injury. Relevance: PDD NOS is a highly prevalent disorder often associated with severe irritability that impedes participation in educational, therapeutic, and vocational programs, with escalating costs of care. Thus, the development of safe and effective pharmacotherapies that improve irritability is clearly relevant to public health.