PsychosisNCT00001198
Evaluating Genetic Risk Factors for Childhood-Onset Schizophrenia
An observational study of Psychosis and Schizophrenia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 years and olderHealthy volunteers can take part
- Conditions the study is for
- Psychosis, Schizophrenia, Genetic Structure
- How many people
- 1,556 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 1984to 10 Oct 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- For Healthy Controls
- Age 6 and above
- Evidence of normal developmental history and normal functioning
- 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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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).
Read the detailed description
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).
- Conditions
- Psychosis, Schizophrenia, Genetic Structure, Childhood Onset Psychotic Disorders, Schizoaffective Disorder
- Keywords
- Schizophrenia, Observational
- Medical subject headings
- Psychotic Disorders, Schizophrenia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start19 Mar 1984
- Study completion10 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PsychosisStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 1,556 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Judith L Rapoport, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001198
- Sponsor's protocol ID
- 840050
- Other IDs
- 84-M-0050
- Status last verified
- 10 Oct 2017
- First submitted
- 3 Nov 1999
- Last updated
- 12 Oct 2017
- Results posted
- No
Publications
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. doi: 10.1097/00004583-199703000-00016.
PubMed 9055518Frazier 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. doi: 10.1016/s0165-1781(97)03062-x.
PubMed 9172272Zahn 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. doi: 10.1001/archpsyc.1997.01830220020003.
PubMed 9337769Dimitriades ME, Schumacher E, Arudchelvam J, Fattinger S, Kurth S, Pugin F, Wehrle F, Jaramillo V, Volk C, Leach S, Buckley A, Driver DI, Markovic A, Rapoport JL, Tarokh L, Huber R, Gerstenberg M. The infraslow fluctuation of sigma power during sleep in young individuals with schizophrenia. Schizophr Res. 2025 Nov;285:295-303. doi: 10.1016/j.schres.2025.09.029. Epub 2025 Oct 13.
PubMed 41086780Loeb FF, Zhou X, Craddock KES, Shora L, Broadnax DD, Gochman P, Clasen LS, Lalonde FM, Berman RA, Berman KF, Rapoport JL, Liu S. Reduced Functional Brain Activation and Connectivity During a Working Memory Task in Childhood-Onset Schizophrenia. J Am Acad Child Adolesc Psychiatry. 2018 Mar;57(3):166-174. doi: 10.1016/j.jaac.2017.12.009. Epub 2017 Dec 28.
PubMed 29496125
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biochemical, Physiological, and Psychological Measures in Normal Controls and Relatives of Psychiatric Patients
- ClinicalTrials.gov ID
- NCT00001198
- Acronym / sponsor ID
- 840050
- Conditions
- Psychosis, Schizophrenia, Genetic Structure, Childhood Onset Psychotic Disorders, Schizoaffective Disorder
- Keywords
- Schizophrenia, Observational
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 1,556 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 19 Mar 1984
- Study completion
- 10 Oct 2017
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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).
Study design
- Observational model
- Family based
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Age 6 and above
- Evidence of normal developmental history and normal functioning
- 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).
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2017.
- Background: PubMed 9055518Casey 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. doi: 10.1097/00004583-199703000-00016.
- Background: PubMed 9172272Frazier 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. doi: 10.1016/s0165-1781(97)03062-x.
- Background: PubMed 9337769Zahn 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. doi: 10.1001/archpsyc.1997.01830220020003.
- Derived from this study: PubMed 41086780Dimitriades ME, Schumacher E, Arudchelvam J, Fattinger S, Kurth S, Pugin F, Wehrle F, Jaramillo V, Volk C, Leach S, Buckley A, Driver DI, Markovic A, Rapoport JL, Tarokh L, Huber R, Gerstenberg M. The infraslow fluctuation of sigma power during sleep in young individuals with schizophrenia. Schizophr Res. 2025 Nov;285:295-303. doi: 10.1016/j.schres.2025.09.029. Epub 2025 Oct 13.
- Derived from this study: PubMed 29496125Loeb FF, Zhou X, Craddock KES, Shora L, Broadnax DD, Gochman P, Clasen LS, Lalonde FM, Berman RA, Berman KF, Rapoport JL, Liu S. Reduced Functional Brain Activation and Connectivity During a Working Memory Task in Childhood-Onset Schizophrenia. J Am Acad Child Adolesc Psychiatry. 2018 Mar;57(3):166-174. doi: 10.1016/j.jaac.2017.12.009. Epub 2017 Dec 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith L Rapoport, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Psychosis and Schizophrenia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001198, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2017.