Genetic, Brain Structure, and Environmental Effects on ADHD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01721720
Recruitment Status : Recruiting
First Posted : November 6, 2012
Last Update Posted : April 19, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Brief Summary:


- Attention deficit hyperactivity disorder (ADHD) is one of the most common and inheritable of all neuropsychiatric disorders. It causes problems with attention and impulse control. However, the genetic component of ADHD has not been fully studied, including how genes interact with the environment. Researchers want to study children and adults who have ADHD. They will look at how genetic, brain structure, and environmental factors affect ADHD in children and adults.


- To study genetic, brain structure, and environmental factors in ADHD in children and adults.


- Individuals at least 3 years of age who have ADHD.


  • Participants will be screened with a physical exam and medical history.
  • Participants will be interviewed about their ADHD. They will also complete behavior and psychological tests. Parents or guardians will complete the tests along with participants under 18 years of age.
  • Participants will provide saliva or blood samples.
  • Participants will also have imaging studies of the brain.
  • Participants under 25 years of age will return once a year to repeat the tests. Those over 25 years of age will have only the one set of tests. Those who are starting stimulant drugs and who are receiving behavioral treatment for the first time will also have another set of tests 12 weeks after the start of treatment.

Condition or disease
Attention Deficit Disorder With Hyperactivity

Detailed Description:


This study aims to provide novel phenotypes for genomic studies into Attention- Deficit Hyperactivity Disorder (ADHD), one of the most common and heritable of all neuropsychiatric disorders. It proposes to split the disorder into neurobiologically more meaningful entities by delineating subgroups based on neurobehavioral profiles. It will also explore factors that impact clinical course, focusing on the neural effects of treatment and the role of the child s social environment.


Using a prospective longitudinal design, a group of children and adolescents with ADHD will be followed. Additionally, families that have several members affected by ADHD will be recruited.


The study will link the onset and clinical course of ADHD with genotype, brain structure and function, behavior and the child s social environment.

Study Type : Observational
Estimated Enrollment : 1200 participants
Time Perspective: Other
Official Title: The Neurobehavioral, Environmental and Genetic Factors Impacting the Clinical Course of Attention Deficit Hyperactivity Disorder
Study Start Date : September 11, 2012

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Three or more years of age with no upper limit for age at time of enrollment. The lower limit of 3 years of age is chosen as it is difficult to diagnose ADHD below this age, but the diagnosis can be reliably made from age 3 onwards. As this study examines the developmental trajectories of ADHD into adulthood, no upper age limit has been set.


Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defined ADHD. The DSM-IV diagnosis of ADHD will be based on the Parent Diagnostic Interview for Children and Adolescents in participants 18 years or age and younger and the Schedule for the Diagnosis of DSM Disorders for participants above 18 years of age. For those of school age, an additional inclusion criterion is the Conners' Teacher Hyperactivity rating greater than 1.5 standard deviations above age- and sex-specific means. ADHD is rarely found in isolation and comorbidity is common. Thus the protocol will include individuals with ADHD and the

following disorders: oppositional defiant disorder, conduct disorder, anxiety disorders (generalized anxiety, specific phobias), tic disorders, mood disorders (dysthymia, depression); specific learning disabilities.

In studying the acute effects of treatment we will include all participants with ADHD who are starting psychostimulant medications for the first time (all psychostimulant preparations are included). We will also include participants with ADHD who are receiving behavioral

management for ADHD for the first time.


We will also include families where there is a incidence of >30% of ADHD in first, second and third degree relatives. This level is chosen as it is well above the incidence rate of ADHD in the general population (~5-7%). Additional inclusion criteria are families where the proband has at least one sibling and only one or neither parent is affected.

We have already identified families of our currently enrolled probands in which at least 4 other first, second or third degree relatives have a current diagnosis of ADHD or had this diagnosis in childhood (and have a similar number of unaffected relatives). We will recruit further families with a similar density of individual affected by ADHD.


Full scale IQ of less than 70. Below this level a child is considered to have global intellectual disability (classified in DSM-IVR as mental retardation). By definition this means the individual cannot be considered to be a healthy control . While many individual with IQ below 70 have symptoms of ADHD, the diagnosis is complicated by problems in assessing attentional abilities.

Finally, there are often issues around the ability to give informed consent in adults with global intellectual disability.

Birth before 32 weeks of gestation. Premature birth can have a profound effect on brain function and structure.

Presence or history of medical conditions that are known to cause alterations in cerebral anatomy detectable by neuroimaging that is current accepted clinical use. Examples include a history of stroke, arteriovenous malformations, agenesis of the corpus callosum, history of neurosurgery, hydrocephalus. Genetic syndromes which are associated with well established alterations of gross cerebral structure- such as NF1, tuberous sclerosis and some forms of epilepsy. Children with known microdeletion syndromes will not be excluded provided (1) the syndrome is not known to be associated with alteration of cerebral anatomy (detectable on current clinical MRI sequences) and (2) other exclusionary criteria do not apply such as global intellectual impairment (defined in this protocol as IQ above 70). Data from these individuals with microdeletion syndromes will not however be included in GWAS due to analytic complications.

Dental braces (as these distort the MRI image). Metal in the body or other contraindications for MRI scanning.

Females who are pregnant will not participate in the MRI scanning only. They will be able to participate in all other parts of the study and can complete the MRI scan post-partum. For participants 60 years or older. Folstein mini mental state examination score of 26 or greater. This is a widely accepted screening test for dementia.

ADDITIONAL EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS ONLY: Presence of any DSM-IV psychiatric disorder in the subject or current use of psychiatric medication.


Some neuropsychiatric disorders are either so rare or associated with such profound alterations of brains structure and function that they will be excluded. This includes psychotic disorders (including schizophrenia, psychosis NOS) bipolar affective disorder; autism, substance dependence; dementia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01721720

Contact: Wendy S Sharp, L.C.S.W. (301) 496-0851
Contact: Wallace P Shaw, M.D. (301) 451-4010

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Principal Investigator: Wallace P Shaw, M.D. National Human Genome Research Institute (NHGRI)

Additional Information:
Responsible Party: National Human Genome Research Institute (NHGRI) Identifier: NCT01721720     History of Changes
Other Study ID Numbers: 120202
First Posted: November 6, 2012    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 17, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):
Attention Deficit Hyperactivity Disorder
Behavioral Phenotype
Brain Development
Complex Disease
Social Networks

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms