Recruiting

Observational Study

Sponsor:

National Institute of Mental Health (NIMH)

Code:

NCT00025935

Conditions

Mood Disorder

Eligibility Criteria

Sex: All

Age: 7 - 60

Healthy Volunteers: Not accepted

Interventions

Lithium

Study Details

Brief summary:

This study seeks to learn more about the symptoms of severe mood dysregulation in children and adolescents ages 7-17. Children and adolescents with severe mood dysregulation (SMD) display chronic anger, sadness, or irritability, as well as hyperarousal (such as insomnia, distractibility, hyperactivity) and extreme responses to frustration (such as frequent, severe temper tantrums). Researchers will describe the moods and behaviors of children with these symptoms and use specialized testing and brain imaging to learn about the brain changes associated with this disorder.

Conditions

Mood Disorder

Study ID

NCT00025935

Start date

Jan 1, 2002

Status verified date

Jul 2, 2026

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 7 - 60

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:

1. Inclusion criteria for children with DMDD, subthreshold DMDD:

1.1.1 Ages 7-17 at the time of recruitment; will be followed in the longitudinal component of the study until age 25.

1.1.2 Abnormal mood (specifically, anger, sadness, and/or irritability), present at least half of the day most days (or at least half the day at least one day per week for subthreshold), and of sufficient severity to be noticeable by people in the child's environment (e.g. parents, teachers, peers).

1.1.3 Compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that is manifest verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property. Such events occur, on average, at least three times a week. For subthreshold DMDD such tantrums occur on average at least once per month.

1.1.4 The symptoms in # 1.1.2, and 1.1.3 above are currently present and have been present for at least 12 months without any symptom-free periods exceeding three months.

1.1.5 The onset of symptoms must be prior to age 10 years.

1.1.6 For DMDD the symptoms are severe in at least in one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers) and at least mild (distractibility, intrusiveness) in a second setting. For subthreshold DMDD, there must be evidence of impairment causing distress to the child or to those around him/her in at least one setting.
2. Parents of children and adolescents with DMDD or subthreshold DMDD enrolled in 02-M-0021

2.1.1. Are capable of performing behavioral tasks and/or scanning.

2.1.2. Speaks English
3. Healthy Volunteer (Control) Children

3.1.1. Control subjects will be group matched to the patients.

3.1.2. Have an identified primary care physician.

3.1.3. Speaks English
4. Healthy Volunteer Adults

4.1.1 Control subjects will be group matched to the patients.

4.1.2. They will have normal physical and neurological examinations by history or checklist

4.1.3. Have an identified primary care physician.

4.1.4 Speaks English
5. Children with Major Depressive Disorder (MDD) Inclusion criteria (all must be met):

5.1.1 Ages 11-17 at the time of recruitment; will be followed in the longitudinal component of the study until age 25.

5.1.2. DSM-IV or DSM-5 Major Depressive Disorder

5.1.2.1 Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

5.1.2.1.1 Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feeling sad, blue, "down in the dumps," or empty) or observation made by others (e.g., appears tearful or about to cry). (In children and adolescents, this may present as an irritable or cranky, rather than sad, mood.)

5.1.2.1.2 Markedly diminished interest or pleasure in all, or almost all, activities every day, such as no interest in hobbies, sports, or other things the person used to enjoy doing.

5.1.2.1.3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day.

5.1.2.1.4. Insomnia (inability to get to sleep or difficulty staying asleep) or hypersomnia (sleeping too much) nearly every day

5.1.2.1.5. Psychomotor agitation (e.g., restlessness, inability to sit still, pacing, pulling at clothes or clothes) or retardation (e.g., slowed speech, movements, quiet talking) nearly every day

5.1.2.1.6. Fatigue, tiredness, or loss of energy nearly every day (e.g., even the smallest tasks, like dressing or washing, seem difficult to do and take longer than usual).

5.1.2.1.7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day (e.g., ruminating over minor past failings).

5.1.2.1.8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (e.g. appears easily distracted, complains of memory difficulties).

5.1.2.1.9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideas without a specific plan, or a suicide attempt or a specific plan for committing suicide

5.1.2.1.10 Symptoms cause clinically significant distress or impairment in social, occupational/academic, or other important areas of functioning.

5.1.2.1.11. The episode is not attributable to the physiological effects of a substance or to another medical condition.

5.1.3. Youth with MDD who are continuing in research as adults must also be receiving psychiatric care for their MDD, if it is ongoing
6. Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

6.1.1. Age 8-17

6.1.2. Currently meets DSM-IV or DSM-5 criteria for ADHD

6.1.3. Subjects with other primary psychiatric disorders including anxiety disorders, dysthymic disorder, past major depression, oppositional defiant disorder, tic disorders, and the learning, communication, and elimination disorders may be accepted

6.1.4. Have an identified primary care physician.

6.1.5. Speaks English

EXCLUSION CRITERIA:

1.3 Exclusion criteria for those with DMDD:

1.3.1 The individual exhibits any of these cardinal bipolar symptoms:

1.3.1.1 Elevated or expansive mood

1.3.1.2 Grandiosity or inflated self-esteem

1.3.1.3 Decreased need for sleep

1.3.1.4 Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences)

1.3.1.5. Has BD symptoms in distinct periods lasting more than 1 day.

1.3.2. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.

1.3.3. IQ< 70

1.3.4. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.

1.3.5. Currently pregnant or lactating

1.3.6. Meets criteria for alcohol or substance abuse with the last three months

2\. Exclusion of parents of children and adolescents with DMDD or subthreshold DMDD

2.1 Have an I.Q. < 70

2.2 Have any serious medical condition or condition that interferes with participation

3.2 Healthy Volunteer Exclusion criteria:

3.2.1. I.Q. < 70;

3.2.2. Any serious medical condition or condition that interferes with fMRI or MEG/EEG scanning, or fNIRS, pregnant or lactating;

3.2.3. Past or current diagnosis of any anxiety disorder (panic disorder, GAD, Separation Anxiety Disorder, Social Phobia), mood disorder (manic or hypomanic episode, major depression), OCD, PTSD, Conduct Disorder, psychosis, current suicidal ideation, Tourette Disorder, Autism Spectrum Disorder or ADHD.

3.2.4. Substance abuse within two months prior to study participation or present substance abuse

3.2.5. History of sexual abuse.

3.2.6. Parent or sibling with Bipolar Disorder, recurrent MDD, or any disorder with psychosis.

4.2 Healthy Volunteer Adult Exclusion criteria:

4.2.1. IQ< 70

4.2.2. Pregnant

4.2.3. Any past or current history of Bipolar Disorder (any manic or hypomanic episode), recurrent MDD, or any disorder with psychosis

5.3 Exclusion criteria for those with MDD:

5.3.1 The individual exhibits any of these cardinal bipolar symptoms:

5.3.1.1 Elevated or expansive mood

5.3.1.2 Grandiosity or inflated self-esteem

5.3.1.3 Decreased need for sleep

5.3.1.4 Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences)

5.3.1.5. Has BD symptoms in distinct periods lasting more than 1 day.

5.3.2. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.

5.3.3. IQ< 70

5.3.4. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.

5.3.5. Currently pregnant or lactating

5.3.6. Meets criteria for alcohol or substance abuse with the last three months

6.2. Exclusion criteria for those with ADHD:

6.2.1. IQ<70

6.2.2. Pregnancy (excludes for scanning only)

6.2.3. Ongoing medical illness or neurological disorder other than ADHD

6.2.4. Any condition that would interfere with the participants' ability to perform research tasks

6.2.5. Current Major Depression

6.2.6. Any past or present manic or hypomanic episode

Study Design

Enrollment

2350 participants

Anticipated

Interventions and Outcome Measures

Arms

Children/adolescents with ADHD

Children/adolescents with ADHD

Children/Adolescents with DMDD or subthreshold DMDD

Children/Adolescents with DMDD or subthreshold DMDD

Children/adolescents with MDD

Children/adolescents with MDD

Healthy volunteer adults

Healthy volunteer adults

Healthy volunteer children/adolescents

Healthy volunteer children/adolescents

Parents of children/adolescents with DMDD or subthreshold DMDD

Parents of children/adolescents with DMDD or subthresdhold DMDD

Interventions

Lithium

Primary outcome measure

  • To examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables [ Time Frame: 20 years ]
  • To examine associations between irritability and clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables [ Time Frame: 20 years ]

Central Contacts and Locations

Central contacts

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222ccopr@nih.gov

More Information

Sponsor

National Institute of Mental Health (NIMH)

Last update posted

Aug 31, 2026

Last verified

Jul 2, 2026

Keywords

  • Neuroimaging
  • Mood Disorder
  • Conduct Disorder
  • Children and Adolescents
  • Affective Neuroscience
  • Natural History
  • Behavioral Dysregulation
  • Behavior
  • Children
  • Adolescent
  • Healthy Volunteer
  • HV
  • Normal Control

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Institute of Mental Health (NIMH) on 2026-08-31.