Evaluating Genetic Risk Factors for Childhood-Onset Schizophrenia
| Status: | Terminated |
|---|---|
| Conditions: | Healthy Studies, Schizophrenia, Psychiatric, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology, Other |
| Healthy: | No |
| Age Range: | 6 - Any |
| Updated: | 10/14/2017 |
| Start Date: | March 19, 1984 |
| End Date: | October 10, 2017 |
Biochemical, Physiological, and Psychological Measures in Normal Controls and Relatives of Psychiatric Patients
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).
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 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. The focus has now shifted to increasing the sample size and evaluation of familial
risk factors including: psychiatric diagnoses of family members; neuropsychological testing,
anatomic and functional brain imaging, and obtaining blood and fibroblasts 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. In
contrast, several findings point to increased genetic risk for these probands.
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
include similar forms of the developmental delays/abnormalities being observed in the COS
probands. Preliminary data suggests greater abnormalities of frontal-parietal circuits for
early onset patients and their relatives than seen in adult onset illness.
We will examine brain development in unrelated healthy volunteers and siblings of our COS
probands by combining resting- and task-related magnetic resonance imaging (MRI) and
magnetoencephalography (MEG) imaging. Imaging studies may lead to greater understanding of
the course, mechanisms, and influences on brain development of high-risk siblings and may
lead to improved understanding of the risk factors, early identification, and optimization of
brain maturation. For more than 20 years, imaging has been done under a separate protocol
(89-M-0006); however, we now plan to incorporate these imaging studies into this protocol (as
well as into our main patient screening and follow-up protocol (03-M-0035) by previously
submitted amendment).
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. The focus has now shifted to increasing the sample size and evaluation of familial
risk factors including: psychiatric diagnoses of family members; neuropsychological testing,
anatomic and functional brain imaging, and obtaining blood and fibroblasts 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. In
contrast, several findings point to increased genetic risk for these probands.
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
include similar forms of the developmental delays/abnormalities being observed in the COS
probands. Preliminary data suggests greater abnormalities of frontal-parietal circuits for
early onset patients and their relatives than seen in adult onset illness.
We will examine brain development in unrelated healthy volunteers and siblings of our COS
probands by combining resting- and task-related magnetic resonance imaging (MRI) and
magnetoencephalography (MEG) imaging. Imaging studies may lead to greater understanding of
the course, mechanisms, and influences on brain development of high-risk siblings and may
lead to improved understanding of the risk factors, early identification, and optimization of
brain maturation. For more than 20 years, imaging has been done under a separate protocol
(89-M-0006); however, we now plan to incorporate these imaging studies into this protocol (as
well as into our main patient screening and follow-up protocol (03-M-0035) by previously
submitted amendment).
- INCLUSION CRITERIA:
i. For Healthy Controls
- Age 6 and above
- Evidence of normal developmental history and normal functioning
ii. For Relatives of Probands
- Ages 6 and above
- Evidence of blood relationship to proband with a disorder under study, with usual
selection of first-degree relatives, and occasional participation of more
distantly-related relatives (e.g., grandparents, aunts/uncles, cousins).
EXCLUSION CRITERIA :
i.For Healthy Controls
- Evidence of medical or neurological disease
- Diagnosis of schizophrenia or schizoaffective disorder or in first-degree relatives by
history, clinical interview, or by structured, diagnostic psychiatric interview
(Diagnostic Interview for Children and Adolescents -IV)
ii.For Relatives of Probands
- Absence of consent on the part of the proband or parent(s) of proband to contact
relatives
- Absence of signed consent or assent by relative(s) to participate
- Lack of consent capacity
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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