A study of children and adolescents (current N=48) with very early onset by age 12 (COS) of DSM-III-R defined schizophrenia with (97-M-0126) is examining the clinical, neurobiological, early neurodevelopmental, genetic, and clinical drug response characteristics of these cases. Earlier studies have documented the continuity between COS and adult onset cases (See Jacobsen and Rapoport, 1998 for review). The focus has now shifted to increasing the sample size and evaluation of familial risk factors including: psychiatric diagnoses of family members; smooth pursuit eye movements; neuropsychological tests deficits, and obtaining blood for cell lines for genetic studies (family members only, this is also covered under 96-M-0060, Dr. Ellen Sidransky).

A study of obstetrical records of COS probands indicated no increase in adverse pre or perinatal events for these cases compared with obstetrical records of their siblings (Nicolson et al submitted). In contrast, several findings point to increased genetic risk for these probands. To date, a total of 5 (10.4%) COS subjects were found to have previously unknown cytogenetic abnormalities (Microdeletion of 22q11 (3 cases), (Usiskin et al, submitted), Mosaic 45X0 (one case) (Kumra et al, 1998) and balanced 1:7 translocation (Gordon et al 1994).

The study of first degree relatives of these very rare cases addresses the hypothesis that risk factors, most probably genetic, are increased in immediate family members relative both to community controls and to the relatives of patients with chronic, treatment resistant, adult-onset schizophrenia (AOS). A second hypothesis is that COS familial risk factors show significant relationship to the developmental delays/abnormalities being observed in the COS probands. As a total of 50 additional COS subjects will be studied over the next 5 years, the pediatric control sample for the probands will also be increased, determined by the need to have concurrent measures for patients and controls to maintain measurement validity. Thus a total of 600 additional subjects are to be studied including 50 controls for COS probands, 150 COS relatives, 150 controls for COS relatives, and 250 relatives of adult onset schizophrenics (AOS).