Typical DevelopmentNCT04631042
Developing Brain, Impulsivity and Compulsivity
An observational study of Typical Development and Obsessive Compulsive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Read more about this study
- Who is it for?
- Ages 6 to 80 years
- Conditions the study is for
- Typical Development, Obsessive Compulsive Disorder, Conduct Disorder
- How many people
- 1,100 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2022to 31 Dec 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals between 6 and 80 years of age with a wide range of impulsivity/compulsivity behaviors - ranging from normal to mildly/extremely impaired - will be recruited. No specific demographic groups will be targeted. Recruitment will be mainly done in the District of Columbia/Maryland/Virginia area, however some participants might travel from elsewhere.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Must be between 6 and 80 years of age.
- Ability of participant to understand and the willingness to sign a written informed consent document.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Cognitively not capable of performing study procedures or lack of capacity to provide informed consent. Indications of a lack of cognitive capacity could include a known full-scale IQ under 70, or a history from the screening interview that implies global intellectual disabilities (e.g., placement in a school for children with intellectual disability etc.)
- Very premature birth (i.e., birth before 32 weeks of gestational age).
- Any known brain abnormalities (e.g., tumor, periventricular leukomalacia, microcephaly) or history of medical conditions known to affect cerebral anatomy (e.g., epilepsy, history of stroke, head injury with a loss of consciousness of one hour or more).
- Psychotic disorders (including schizophrenia, psychosis not otherwise specified).
- Dementia, or other conditions that, in the opinion of the investigators, would impede compliance or possibly hinder completion of the study.
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- Pregnant women.
- Any other medical or psychiatric condition that in the opinion of the PI may confound study data/assessments.
- Additional exclusion criteria for optional MRI procedure:
- 1. Individuals who are not able to receive an MRI (e.g., metal bioimplants, claustrophobia, inability to lie flat on their backs, pregnant women, and any other contraindications for MRI scanning according to the NMR Center MRI safety guidelines).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: An Observational Study of the Developing Brain, Impulsivity and Compulsivity
Background:
Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Differences in genes may also play a role.
Read more
Objective:
To learn about genetic \& brain features that explain why levels of impulsivity and compulsivity vary across people.
Eligibility:
People ages 6 - 80
Design:
Participants will be screened with a medical history and medical record review.
Participants will talk about their mental and behavioral development. They may discuss topics like drug use and sexual activity. They will complete surveys about their compulsivity and impulsivity. Parents of child participants may also complete these surveys.
Participants may take memory, attention, and thinking tests. They may give blood or saliva samples for gene studies and they may give blood to make induced pluripotent stem cells. Participants may have their face and irises photographs taken.
Participants may have a magnetic resonance imaging scan. It will take pictures of their brain. The scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A coil will be placed over their head. They will lie still, watch a movie, and play a game.
Participants may ask family members to join the study. Researchers are particularly interested in recruiting twin pairs to the study.
Participants under age 25 may repeat these tests every 1-2 years until they turn 25 or until the study ends. For those over age 25, participation will last less than 1 month.
Read the detailed description
Study Description:
Many neuropsychiatric disorders have extreme impairing impulsivity and compulsivity behaviors at their core. We hypothesized that the development of symptoms of impulsivity and compulsivity during childhood/adolescence and early adulthood will be associated with atypical trajectories of brain features including cortical glutamate (the main excitatory neurotransmitter) and functional/structural brain connectivity. Additionally, we hypothesize that cortical glutamate will be under genetic control (i.e., heritable) and that common genetic variant risk for disorders characterized by extreme impulsivity (e.g., attention deficit hyperactivity disorder) and by extreme compulsivity (e.g., obsessive compulsive disorder, autism spectrum disorder) will also be associated with atypical cortical glutamate trajectories. To elucidate the relationships between the developing brain, compulsivity/impulsivity and genomics, we will collect clinical assessments including clinician-led interviews, neurobehavioral assessments, neuroimaging data, and genomic samples using 1) a prospective longitudinal design to answer developmental hypotheses; 2) a twin design to assess heritability hypotheses.
Objectives:
Primary Objective:
- To assess the effects of impulsivity and compulsivity on the developmental trajectories of cortical glutamate.
- To determine the heritability of cortical glutamate.
Secondary Objectives:
- To establish the reliability of glutamate measurements.
- To examine the impact of atypical glutamate levels on developing structural and functional connections within the fronto-striatal circuits.
- To assess within twin pair differences in neurodevelopmental markers (cortical glutamate, structural/functional MRI) in relation to differences in symptom domains.
Endpoints:
Primary Endpoint:
- Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity.
- Heritability of cortical glutamate (proportion of variance explained by additive genetic factors).
Secondary Endpoints:
- 1) Glutamate levels estimated at 3 Tesla at short intervals to establish test-retest reliability.
- Glutamate levels estimated at both 3 Tesla and 7 Tesla (cross scanner validation).
- Measures of the brain's structural and functional connectivity.
- Within twin-pair differences in neurodevelopmental markers symptom domains (impulsivity/compulsivity).
- Conditions
- Typical Development, Obsessive Compulsive Disorder, Conduct Disorder, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder
- Keywords
- Neurodevelopmental disorder, Twin, Natural History, Heritability, Glutamate, developmental trajectory, Brain Connectivity
- Medical subject headings
- Obsessive-Compulsive Disorder, Conduct Disorder, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| impulsive compulsive | Individuals between 6 and 80 years of age with a wide range of impulsivity/compulsivity behaviors - ranging from normal to mildly/extremely impaired. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glutamate concentration measured using Magnetic Resonance Spectroscopy
Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity.
Measured: Yearly if possible
Heritability of cortical glutamate (proportion of variance explained by additive genetic factors).
Degree to which glutamate levels are under genetic control.
Measured: Baseline
Secondary outcomes (3)
Structural and functional connectivity
Structural and functional connectivity measured throughout development using Magnetic Resonance Imaging.
Measured: Yearly if possible
Glutamate levels
Glutamate measurement at 7 Tesla is now the gold standard for glutamate measurements, against which we will compare measurements at 3 Tesla.
Measured: weeks to months
Differences in glutamate levels and other neurodevelopmental markers within twin pairs.
Differences in twin characteristics will be measured through clinical symptom assessment, biomarkers, Magnetic Resonance Imaging, neuropsychological testing, and questionnaires.
Measured: Yearly if possible
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start30 Sep 2022
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Typical DevelopmentStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Tonya J White, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04631042
- Sponsor's protocol ID
- 200147
- Other IDs
- 20-HG-0147
- Status last verified
- 23 Sep 2026
- First submitted
- 14 Nov 2020
- Last updated
- 25 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All de-identified medical information will be placed in a NIH repository (e.g., Biomedical Translational Research Information System (BTRIS)) in accordance to NIH policies. We will also share genomic and phenotypic data in controlled access databases such as dbGAP (database of Genotypes and Phenotypes). Other databases may be used as approved by NIH for the sharing of de-identified data.
Publications
Ziegler G, Hauser TU, Moutoussis M, Bullmore ET, Goodyer IM, Fonagy P, Jones PB; NSPN Consortium; Lindenberger U, Dolan RJ. Compulsivity and impulsivity traits linked to attenuated developmental frontostriatal myelination trajectories. Nat Neurosci. 2019 Jun;22(6):992-999. doi: 10.1038/s41593-019-0394-3. Epub 2019 May 13.
PubMed 31086316Naaijen J, Lythgoe DJ, Amiri H, Buitelaar JK, Glennon JC. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies. Neurosci Biobehav Rev. 2015 May;52:74-88. doi: 10.1016/j.neubiorev.2015.02.009. Epub 2015 Feb 21.
PubMed 25712432Fineberg NA, Chamberlain SR, Goudriaan AE, Stein DJ, Vanderschuren LJ, Gillan CM, Shekar S, Gorwood PA, Voon V, Morein-Zamir S, Denys D, Sahakian BJ, Moeller FG, Robbins TW, Potenza MN. New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr. 2014 Feb;19(1):69-89. doi: 10.1017/S1092852913000801.
PubMed 24512640
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study of the Developing Brain, Impulsivity and Compulsivity
- ClinicalTrials.gov ID
- NCT04631042
- Acronym / sponsor ID
- 200147
- Conditions
- Typical Development, Obsessive Compulsive Disorder, Conduct Disorder, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder
- Keywords
- Neurodevelopmental disorder, Twin, Natural History, Heritability, Glutamate, developmental trajectory, Brain Connectivity
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,100 participants (estimated)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 30 Sep 2022 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 17 Nov 2020 (actual)
- 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.
Background:
Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Differences in genes may also play a role.
Objective:
To learn about genetic \& brain features that explain why levels of impulsivity and compulsivity vary across people.
Eligibility:
People ages 6 - 80
Design:
Participants will be screened with a medical history and medical record review.
Participants will talk about their mental and behavioral development. They may discuss topics like drug use and sexual activity. They will complete surveys about their compulsivity and impulsivity. Parents of child participants may also complete these surveys.
Participants may take memory, attention, and thinking tests. They may give blood or saliva samples for gene studies and they may give blood to make induced pluripotent stem cells. Participants may have their face and irises photographs taken.
Participants may have a magnetic resonance imaging scan. It will take pictures of their brain. The scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A coil will be placed over their head. They will lie still, watch a movie, and play a game.
Participants may ask family members to join the study. Researchers are particularly interested in recruiting twin pairs to the study.
Participants under age 25 may repeat these tests every 1-2 years until they turn 25 or until the study ends. For those over age 25, participation will last less than 1 month.
Detailed description
Study Description:
Many neuropsychiatric disorders have extreme impairing impulsivity and compulsivity behaviors at their core. We hypothesized that the development of symptoms of impulsivity and compulsivity during childhood/adolescence and early adulthood will be associated with atypical trajectories of brain features including cortical glutamate (the main excitatory neurotransmitter) and functional/structural brain connectivity. Additionally, we hypothesize that cortical glutamate will be under genetic control (i.e., heritable) and that common genetic variant risk for disorders characterized by extreme impulsivity (e.g., attention deficit hyperactivity disorder) and by extreme compulsivity (e.g., obsessive compulsive disorder, autism spectrum disorder) will also be associated with atypical cortical glutamate trajectories. To elucidate the relationships between the developing brain, compulsivity/impulsivity and genomics, we will collect clinical assessments including clinician-led interviews, neurobehavioral assessments, neuroimaging data, and genomic samples using 1) a prospective longitudinal design to answer developmental hypotheses; 2) a twin design to assess heritability hypotheses.
Objectives:
Primary Objective:
- To assess the effects of impulsivity and compulsivity on the developmental trajectories of cortical glutamate.
- To determine the heritability of cortical glutamate.
Secondary Objectives:
- To establish the reliability of glutamate measurements.
- To examine the impact of atypical glutamate levels on developing structural and functional connections within the fronto-striatal circuits.
- To assess within twin pair differences in neurodevelopmental markers (cortical glutamate, structural/functional MRI) in relation to differences in symptom domains.
Endpoints:
Primary Endpoint:
- Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity.
- Heritability of cortical glutamate (proportion of variance explained by additive genetic factors).
Secondary Endpoints:
- 1) Glutamate levels estimated at 3 Tesla at short intervals to establish test-retest reliability.
- Glutamate levels estimated at both 3 Tesla and 7 Tesla (cross scanner validation).
- Measures of the brain's structural and functional connectivity.
- Within twin-pair differences in neurodevelopmental markers symptom domains (impulsivity/compulsivity).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| impulsive compulsive | – | –Individuals between 6 and 80 years of age with a wide range of impulsivity/compulsivity behaviors - ranging from normal to mildly/extremely impaired. |
Who may qualify
- Ages
- 6 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals between 6 and 80 years of age with a wide range of impulsivity/compulsivity behaviors - ranging from normal to mildly/extremely impaired - will be recruited. No specific demographic groups will be targeted. Recruitment will be mainly done in the District of Columbia/Maryland/Virginia area, however some participants might travel from elsewhere.
Key inclusion criteria (4 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Must be between 6 and 80 years of age.
- Ability of participant to understand and the willingness to sign a written informed consent document.
Key exclusion criteria (10 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Cognitively not capable of performing study procedures or lack of capacity to provide informed consent. Indications of a lack of cognitive capacity could include a known full-scale IQ under 70, or a history from the screening interview that implies global intellectual disabilities (e.g., placement in a school for children with intellectual disability etc.)
- Very premature birth (i.e., birth before 32 weeks of gestational age).
- Any known brain abnormalities (e.g., tumor, periventricular leukomalacia, microcephaly) or history of medical conditions known to affect cerebral anatomy (e.g., epilepsy, history of stroke, head injury with a loss of consciousness of one hour or more).
- Psychotic disorders (including schizophrenia, psychosis not otherwise specified).
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
Glutamate concentration measured using Magnetic Resonance Spectroscopy
Time frame: Yearly if possible
Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity.
Heritability of cortical glutamate (proportion of variance explained by additive genetic factors).
Time frame: Baseline
Degree to which glutamate levels are under genetic control.
3 secondary outcomes
Structural and functional connectivity
Time frame: Yearly if possible
Glutamate levels
Time frame: weeks to months
Differences in glutamate levels and other neurodevelopmental markers within twin pairs.
Time frame: Yearly if possible
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Background: PubMed 31086316Ziegler G, Hauser TU, Moutoussis M, Bullmore ET, Goodyer IM, Fonagy P, Jones PB; NSPN Consortium; Lindenberger U, Dolan RJ. Compulsivity and impulsivity traits linked to attenuated developmental frontostriatal myelination trajectories. Nat Neurosci. 2019 Jun;22(6):992-999. doi: 10.1038/s41593-019-0394-3. Epub 2019 May 13.
- Background: PubMed 25712432Naaijen J, Lythgoe DJ, Amiri H, Buitelaar JK, Glennon JC. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies. Neurosci Biobehav Rev. 2015 May;52:74-88. doi: 10.1016/j.neubiorev.2015.02.009. Epub 2015 Feb 21.
- Background: PubMed 24512640Fineberg NA, Chamberlain SR, Goudriaan AE, Stein DJ, Vanderschuren LJ, Gillan CM, Shekar S, Gorwood PA, Voon V, Morein-Zamir S, Denys D, Sahakian BJ, Moeller FG, Robbins TW, Potenza MN. New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr. 2014 Feb;19(1):69-89. doi: 10.1017/S1092852913000801.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All de-identified medical information will be placed in a NIH repository (e.g., Biomedical Translational Research Information System (BTRIS)) in accordance to NIH policies. We will also share genomic and phenotypic data in controlled access databases such as dbGAP (database of Genotypes and Phenotypes). Other databases may be used as approved by NIH for the sharing of de-identified data.
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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.
Tonya J White, 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 Typical Development and Obsessive Compulsive Disorder, 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 4 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 25 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tonya J White, M.D. ((301) 496-5192, tonya.white@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glutamate concentration measured using Magnetic Resonance Spectroscopy (time frame: Yearly if possible). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04631042, which also lists 3 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 25 Sep 2026.