A study of children and adolescents (current N=100) 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 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).

A study of children and adolescents (current N = 100) with very early onset by age 12 (COS) of DSM-III-R defined schizophrenia is examining the clinical, neurobiological, early neurodevelopmental, genetic, and clinical drug response characteristics of these cases, under Protocols 97-M-0126 and 03-M-0035. 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; neuropsychological tests deficits, and obtaining blood for cell lines for genetic studies.

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 well 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 a 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.

• Healthy
• Schizophrenia

• Casey BJ, Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Schubert AB, Vauss YC, Vaituzis AC, Dickstein DP, Sarfatti SE, Rapoport JL. Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1997 Mar;36(3):374-83.
• Frazier JA, Alaghband-Rad J, Jacobsen L, Lenane MC, Hamburger S, Albus K, Smith A, McKenna K, Rapoport JL. Pubertal development and onset of psychosis in childhood onset schizophrenia. Psychiatry Res. 1997 Apr 18;70(1):1-7.
• Zahn TP, Jacobsen LK, Gordon CT, McKenna K, Frazier JA, Rapoport JL. Autonomic nervous system markers of psychopathology in childhood-onset schizophrenia. Arch Gen Psychiatry. 1997 Oct;54(10):904-12.

• INCLUSION CRITERIA:

Inclusion criteria for healthy controls will continue to be:

1. Ages 6-70
2. Evidence of normal developmental history and normal functioning.

Inclusion criteria for relatives of probands will continue to be:

1. Ages 6-70
2. Evidence of blood relationship to proband with a disorder under study, with usual selection of first-degree relatives.

EXCLUSION CRITERIA:

Exclusion criteria for community controls are:

1. Evidence of medical or neurological disease.

2. Diagnosis of schizophrenia or schizoaffective disorder in the control or in first degree relatives by history, clinical interview, or by structured, diagnostic psychiatric interview (Diagnostic Interview for Children and Adolescents -IV).

   Exclusion criteria for relatives of probands:

3. Absence of consent on the part of the proband or parent(s) of proband to contact relatives.
4. Absence of signed consent or assent by relative(s) to participate.