Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder

NCT00025935 | Recruiting

• 2 other identifiers: 02002102-M-0021
• Study Type: observational
• Target: 2,350
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• To examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables

  Individuals with full or subthreshold DMDD and/or MDD, ADHD, anxiety (see protocol 00-M-0192), and healthy volunteers (see protocol 00-M-0198).

  20 years

• To examine associations between irritability and clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables

  Individuals with full or subthreshold DMDD and/or MDD, ADHD, anxiety (see protocol 00-M-0192), and healthy volunteers (see protocol 00-M-0198).

  20 years

Study Arms (6)

Children/adolescents with ADHD

Children/adolescents with ADHD

Drug: Lithium

Children/Adolescents with DMDD or subthreshold DMDD

Children/Adolescents with DMDD or subthreshold DMDD

Drug: Lithium

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 DRUG

Children/Adolescents with DMDD or subthreshold DMDD; Children/adolescents with ADHD

Eligibility Criteria

• Age: 7 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

There are 6 separate populations being studied in this protocol: 1.Children and adolescents between the ages of 7-17 years old who meet criteria for DMDD or subthreshold DMDD. 2.Parents of children and adolescents, who meet criteria for DMDD or subthreshold DMDD and are enrolled in 02-M-0021, and are 25 - 59 years old will be studied. 3.Healthy volunteer children and adolescents between the ages of 7-17 years old. 4.Healthy volunteer adults between the ages of 18-25 years old. 5.Children and adolescents between the ages of 12-17 years old who meet criteria for major depressive disorder (MDD). 6.Children and adolescents between the ages of 8-17 years who meet criteria for attention-deficit /hyperactivity disorder (ADHD) who do not have a mood disorder.

You may qualify if:

• Ages 7-17 at the time of recruitment; will be followed in the longitudinal component of the study until age 25.
• 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).
• 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.
• 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.
• The onset of symptoms must be prior to age 10 years.
• 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.
• Parents of children and adolescents with DMDD or subthreshold DMDD enrolled in 02-M-0021
• Are capable of performing behavioral tasks and/or scanning.
• Speaks English
• Healthy Volunteer (Control) Children
• Control subjects will be group matched to the patients.
• Have an identified primary care physician.
• Speaks English
• Healthy Volunteer Adults
• Control subjects will be group matched to the patients.

You may not qualify if:

• The individual exhibits any of these cardinal bipolar symptoms:
• Elevated or expansive mood
• Grandiosity or inflated self-esteem
• Decreased need for sleep
• Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences)
• Has BD symptoms in distinct periods lasting more than 1 day.
• Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.
• IQ\< 70
• The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.
• Currently pregnant or lactating
• Meets criteria for alcohol or substance abuse with the last three months
• Have an I.Q. \< 70
• Have any serious medical condition or condition that interferes with participation
• I.Q. \< 70;
• Any serious medical condition or condition that interferes with fMRI or MEG/EEG scanning, or fNIRS, pregnant or lactating;

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (28)

• Haller SP, Stoddard J, Cardenas SI, Dombek K, MacGillivray C, Botz-Zapp C, Bui HNT, Stavish CM, Kircanski K, Jones M, Brotman MA. Differentiating neural sensitivity and bias during face-emotion processing in youth: a computational approach. Soc Cogn Affect Neurosci. 2024 Jun 13;19(1):nsae034. doi: 10.1093/scan/nsae034.

  PMID: 38794949 DERIVED

• Tseng WL, Naim R, Chue A, Shaughnessy S, Meigs J, Pine DS, Leibenluft E, Kircanski K, Brotman MA. Network analysis of ecological momentary assessment identifies frustration as a central node in irritability. J Child Psychol Psychiatry. 2023 Aug;64(8):1212-1221. doi: 10.1111/jcpp.13794. Epub 2023 Mar 28.

  PMID: 36977629 DERIVED

• Linke JO, Haller SP, Xu EP, Nguyen LT, Chue AE, Botz-Zapp C, Revzina O, Perlstein S, Ross AJ, Tseng WL, Shaw P, Brotman MA, Pine DS, Gotts SJ, Leibenluft E, Kircanski K. Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability. J Am Acad Child Adolesc Psychiatry. 2023 Jun;62(6):684-695. doi: 10.1016/j.jaac.2022.11.009. Epub 2022 Dec 21.

  PMID: 36563874 DERIVED

• Naim R, Shaughnessy S, Smith A, Karalunas SL, Kircanski K, Brotman MA. Real-time assessment of positive and negative affective fluctuations and mood lability in a transdiagnostic sample of youth. Depress Anxiety. 2022 Dec;39(12):870-880. doi: 10.1002/da.23293. Epub 2022 Nov 3.

  PMID: 36325887 DERIVED

• Haller SP, Archer C, Jeong A, Jaffe A, Jones EL, Harrewijn A, Naim R, Linke JO, Stoddard J, Brotman MA. Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors. Child Psychiatry Hum Dev. 2024 Feb;55(1):206-218. doi: 10.1007/s10578-022-01382-z. Epub 2022 Jul 6.

  PMID: 35794298 DERIVED

• Zik J, Deveney CM, Ellingson JM, Haller SP, Kircanski K, Cardinale EM, Brotman MA, Stoddard J. Understanding Irritability in Relation to Anger, Aggression, and Informant in a Pediatric Clinical Population. J Am Acad Child Adolesc Psychiatry. 2022 May;61(5):711-720. doi: 10.1016/j.jaac.2021.08.012. Epub 2021 Aug 23.

  PMID: 34438022 DERIVED

• Naim R, Goodwin MS, Dombek K, Revzina O, Agorsor C, Lee K, Zapp C, Freitag GF, Haller SP, Cardinale E, Jangraw D, Brotman MA. Cardiovascular reactivity as a measure of irritability in a transdiagnostic sample of youth: Preliminary associations. Int J Methods Psychiatr Res. 2021 Dec;30(4):e1890. doi: 10.1002/mpr.1890. Epub 2021 Aug 13.

  PMID: 34390050 DERIVED

• Haller SP, Stoddard J, Botz-Zapp C, Clayton M, MacGillivray C, Perhamus G, Stiles K, Kircanski K, Penton-Voak IS, Bar-Haim Y, Munafo M, Towbin KE, Brotman MA. A Randomized Controlled Trial of Computerized Interpretation Bias Training for Disruptive Mood Dysregulation Disorder: A Fast-Fail Study. J Am Acad Child Adolesc Psychiatry. 2022 Jan;61(1):37-45. doi: 10.1016/j.jaac.2021.05.022. Epub 2021 Jun 17.

  PMID: 34147585 DERIVED

• Naim R, Kircanski K, Gold A, German RE, Davis M, Perlstein S, Clayton M, Revzina O, Brotman MA. Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol. BMJ Open. 2021 Mar 10;11(3):e039169. doi: 10.1136/bmjopen-2020-039169.

  PMID: 33692176 DERIVED

• Scheinost D, Dadashkarimi J, Finn ES, Wambach CG, MacGillivray C, Roule AL, Niendam TA, Pine DS, Brotman MA, Leibenluft E, Tseng WL. Functional connectivity during frustration: a preliminary study of predictive modeling of irritability in youth. Neuropsychopharmacology. 2021 Jun;46(7):1300-1306. doi: 10.1038/s41386-020-00954-8. Epub 2021 Jan 21.

  PMID: 33479511 DERIVED

• Linke JO, Abend R, Kircanski K, Clayton M, Stavish C, Benson BE, Brotman MA, Renaud O, Smith SM, Nichols TE, Leibenluft E, Winkler AM, Pine DS. Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates. Biol Psychiatry. 2021 Mar 15;89(6):579-587. doi: 10.1016/j.biopsych.2020.10.018. Epub 2020 Nov 9.

  PMID: 33386133 DERIVED

• Haller SP, Stoddard J, Pagliaccio D, Bui H, MacGillivray C, Jones M, Brotman MA. Computational Modeling of Attentional Impairments in Disruptive Mood Dysregulation and Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2021 May;60(5):637-645. doi: 10.1016/j.jaac.2020.08.468. Epub 2020 Nov 24.

  PMID: 33242544 DERIVED

• Haller SP, Kircanski K, Stringaris A, Clayton M, Bui H, Agorsor C, Cardenas SI, Towbin KE, Pine DS, Leibenluft E, Brotman MA. The Clinician Affective Reactivity Index: Validity and Reliability of a Clinician-Rated Assessment of Irritability. Behav Ther. 2020 Mar;51(2):283-293. doi: 10.1016/j.beth.2019.10.005. Epub 2019 Nov 27.

  PMID: 32138938 DERIVED

• Linke JO, Adleman NE, Sarlls J, Ross A, Perlstein S, Frank HR, Towbin KE, Pine DS, Leibenluft E, Brotman MA. White Matter Microstructure in Pediatric Bipolar Disorder and Disruptive Mood Dysregulation Disorder. J Am Acad Child Adolesc Psychiatry. 2020 Oct;59(10):1135-1145. doi: 10.1016/j.jaac.2019.05.035. Epub 2019 Jul 19.

  PMID: 31330239 DERIVED

• Cardinale EM, Kircanski K, Brooks J, Gold AL, Towbin KE, Pine DS, Leibenluft E, Brotman MA. Parsing neurodevelopmental features of irritability and anxiety: Replication and validation of a latent variable approach. Dev Psychopathol. 2019 Aug;31(3):917-929. doi: 10.1017/S095457941900035X. Epub 2019 May 8.

  PMID: 31064595 DERIVED

• Kryza-Lacombe M, Brotman MA, Reynolds RC, Towbin K, Pine DS, Leibenluft E, Wiggins JL. Neural mechanisms of face emotion processing in youths and adults with bipolar disorder. Bipolar Disord. 2019 Jun;21(4):309-320. doi: 10.1111/bdi.12768. Epub 2019 Apr 1.

  PMID: 30851221 DERIVED

• Tseng WL, Deveney CM, Stoddard J, Kircanski K, Frackman AE, Yi JY, Hsu D, Moroney E, Machlin L, Donahue L, Roule A, Perhamus G, Reynolds RC, Roberson-Nay R, Hettema JM, Towbin KE, Stringaris A, Pine DS, Brotman MA, Leibenluft E. Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths. Am J Psychiatry. 2019 Jan 1;176(1):67-76. doi: 10.1176/appi.ajp.2018.18040491. Epub 2018 Oct 19.

  PMID: 30336704 DERIVED

• Vidal-Ribas P, Brotman MA, Salum GA, Kaiser A, Meffert L, Pine DS, Leibenluft E, Stringaris A. Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder. Depress Anxiety. 2018 Dec;35(12):1207-1217. doi: 10.1002/da.22810. Epub 2018 Jul 13.

  PMID: 30004611 DERIVED

• Kircanski K, White LK, Tseng WL, Wiggins JL, Frank HR, Sequeira S, Zhang S, Abend R, Towbin KE, Stringaris A, Pine DS, Leibenluft E, Brotman MA. A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth. JAMA Psychiatry. 2018 Jun 1;75(6):631-639. doi: 10.1001/jamapsychiatry.2018.0468.

  PMID: 29625429 DERIVED

• Stringaris A, Vidal-Ribas P, Brotman MA, Leibenluft E. Practitioner Review: Definition, recognition, and treatment challenges of irritability in young people. J Child Psychol Psychiatry. 2018 Jul;59(7):721-739. doi: 10.1111/jcpp.12823. Epub 2017 Oct 30.

  PMID: 29083031 DERIVED

• Brotman MA, Kircanski K, Leibenluft E. Irritability in Children and Adolescents. Annu Rev Clin Psychol. 2017 May 8;13:317-341. doi: 10.1146/annurev-clinpsy-032816-044941.

  PMID: 28482689 DERIVED

• Brotman MA, Kircanski K, Stringaris A, Pine DS, Leibenluft E. Irritability in Youths: A Translational Model. Am J Psychiatry. 2017 Jun 1;174(6):520-532. doi: 10.1176/appi.ajp.2016.16070839. Epub 2017 Jan 20.

  PMID: 28103715 DERIVED

• Wiggins JL, Brotman MA, Adleman NE, Kim P, Wambach CG, Reynolds RC, Chen G, Towbin K, Pine DS, Leibenluft E. Neural Markers in Pediatric Bipolar Disorder and Familial Risk for Bipolar Disorder. J Am Acad Child Adolesc Psychiatry. 2017 Jan;56(1):67-78. doi: 10.1016/j.jaac.2016.10.009. Epub 2016 Nov 2.

  PMID: 27993231 DERIVED

• Stoddard J, Gotts SJ, Brotman MA, Lever S, Hsu D, Zarate C, Ernst M, Pine DS, Leibenluft E. Aberrant intrinsic functional connectivity within and between corticostriatal and temporal-parietal networks in adults and youth with bipolar disorder. Psychol Med. 2016 May;46(7):1509-22. doi: 10.1017/S0033291716000143. Epub 2016 Feb 29.

  PMID: 26924633 DERIVED

• Wiggins JL, Brotman MA, Adleman NE, Kim P, Oakes AH, Reynolds RC, Chen G, Pine DS, Leibenluft E. Neural Correlates of Irritability in Disruptive Mood Dysregulation and Bipolar Disorders. Am J Psychiatry. 2016 Jul 1;173(7):722-30. doi: 10.1176/appi.ajp.2015.15060833. Epub 2016 Feb 19.

  PMID: 26892942 DERIVED

• Stoddard J, Sharif-Askary B, Harkins EA, Frank HR, Brotman MA, Penton-Voak IS, Maoz K, Bar-Haim Y, Munafo M, Pine DS, Leibenluft E. An Open Pilot Study of Training Hostile Interpretation Bias to Treat Disruptive Mood Dysregulation Disorder. J Child Adolesc Psychopharmacol. 2016 Feb;26(1):49-57. doi: 10.1089/cap.2015.0100. Epub 2016 Jan 8.

  PMID: 26745832 DERIVED

• Tseng WL, Thomas LA, Harkins E, Pine DS, Leibenluft E, Brotman MA. Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation. Soc Cogn Affect Neurosci. 2016 Jan;11(1):78-88. doi: 10.1093/scan/nsv087. Epub 2015 Jul 2.

  PMID: 26137973 DERIVED

• Deveney CM, Hommer RE, Reeves E, Stringaris A, Hinton KE, Haring CT, Vidal-Ribas P, Towbin K, Brotman MA, Leibenluft E. A prospective study of severe irritability in youths: 2- and 4-year follow-up. Depress Anxiety. 2015 May;32(5):364-72. doi: 10.1002/da.22336. Epub 2014 Dec 12.

  PMID: 25504765 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mood Disorders; Conduct Disorder; Behavior

Interventions

Lithium

Condition Hierarchy (Ancestors)

Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Melissa A Brotman, Ph.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa A Brotman, Ph.D.

CONTACT

(301) 435-6645; melissa.brotman@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2001
• First Posted: November 1, 2001
• Study Start: January 1, 2002
• Last Updated: May 1, 2026

Record last verified: 2026-01-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)