NCT00006177

Brief Summary

This research protocol seeks to learn more about bipolar disorder in children and adolescents ages 6-17. Researchers will describe the moods and behaviors of children with bipolar disorder and use specialized testing and brain imaging to learn about specific brain changes associated with the disorder. This protocol studies children who have been diagnosed with bipolar disorder, and those who have a sibling or parent with bipolar disorder and are thus considered "at risk" for developing the disorder.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,303

participants targeted

Target at P75+ for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 11, 2000

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

August 12, 2000

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 14, 2000

Completed
Last Updated

March 17, 2023

Status Verified

March 8, 2023

First QC Date

August 12, 2000

Last Update Submit

March 16, 2023

Conditions

Bipolar DisorderMood DisordersAttention Deficit Hyerpactivity Disorder

Keywords

EmotionAffective NeuroscienceBipolar DisorderChildChild BipolarNatural HistoryBPDAdolescent Bipolar

Outcome Measures

Primary Outcomes (3)

  • Objective 1: clinical manifestations

    (1) clinical interviews \[e.g., Schedule for Affective Disorders and Schizophrenia for School-Age Children-present and lifetime version, K-SADS-PL, (Kaufman et al., 1997); Structured Clinical Interview for DSM-IV-TR Axis I Disorders, SCID (First et al., 2002)\]; (2) clinical and mood rating assessments (e.g., Children's Depression Rating Scale (Poznanski et al., 1984), Young Mania Rating Scale (Young et al., 1978), Pediatric Anxiety Rating (2002), EMA; (3) episode setting via detailed clinical interview at baseline and every 6 month follow up phone call (4) parent-report and self-report \[e.g., The Screen for Child Anxiety Related Emotional Disorders SCARED (Birmaher et al., 1997); Social Responsiveness Scale, SRS (Constantino et al., 2003, Granader et al.); Child Behavior Checklist CBCL (Achenbach, 1991)\].

    lifetime of protocol

  • Objective 2: behavioral, neuropsychological, neurophysiological, and neuroanatomical correlates

    1\) behavioral performance (e.g., accuracy, response time) on tasks assessing attention, emotion, and attention-emotion interactions; (e.g., Stop/Change task, CPT/Flanker, Decision Making tasks) 2) neuropsychological performance (e.g., performance and verbal IQ) 3) brain activation using functional MRI during tasks assessing attention, emotion, and attention-emotion interactions; 4) structural MRI to examine the size, shape and development of grey matter; 5) Diffusion Tensor Imaging (DTI) to measure white matter track myelination; 6) resting state imaging to test functional connectivity between prefrontal regions and the amygdala

    lifetime of protocol

  • Objective 3: genetic and familial correlates

    (1) clinical interviews \[e.g., Schedule for Affective Disorders and Schizophrenia for School-Age Children-present and lifetime version, K-SADS-PL, (Kaufman et al., 1997); Structured Clinical Interview for DSM-IV-TR Axis I Disorders, SCID (First et al., 2002)\] to examine the rate of various diagnoses in relatives of individuals with BD (2) genetic material to compare genetic polymorphisms in BSD, their relatives and controls (3) relationship between genetic material and performance on behavioral tasks and activation during fMRI paradigms (4) behavioral performance on standardized paradigms; brain activation using functional MRI; size, shape and development of several ROIs using structural MRI; Diffusion Tensor Imaging (DTI); and, Resting State in individuals with a BD relative

    lifetime of protocol

Study Arms (8)

Adult bipolar patients

Adult bipolar patients

Adult Extended Relatives of BD probands

Adult Extended Relatives of BD probands

Bipolar Children and Youth

Bipolar Children and Youth

Child/Adolescent Extended Relatives of BD probands

Child/Adolescent Extended Relatives of BD probands

Children with ADHD only (controls)

Children with ADHD only (controls)

First degree relatives of BD patients

First degree relatives of BD patients

Healthy volunteer adults (parents or not)

Healthy volunteer adults (parents or not)

Healthy volunteer children and youth

Healthy volunteer children and youth

Eligibility Criteria

Age3 Years - 58 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

There are 11 separate populations being studied in this protocol: 1. Children and adolescents between the ages of 6-17 years old who meet criteria for BSD. 2. Adults between the ages of 18-58 years old who meet criteria for BD, including those age 18-25 with BSD. 3. Control populations of: a) Healthy volunteer children and adolescents between the ages of 3-17 years old, b) Parents of healthy volunteer children or healthy adults in research, c) Children 8-17 years old with attention deficit hyperactivity disorder (ADHD), who do not have a mood disorder. 4. First and second-degree biological relatives of those in (B.1) or (B.2), above, and are between 3-58 years old. 5. A subgroup of these cohorts will be Old Order Amish individuals who fulfill eligibility for (1), (2), (3a), (3b), or (4).

You may not qualify if:

  • Pediatric patients with bipolar disorder or SMIBRD:
  • Age 6-17
  • Meet DSM criteria for BD
  • Have a primary caregiver who can accompany him or her on trips to NIMH and provide reliable history and information.
  • Have a psychiatrist who provides clinical care for their BSD.
  • Be able to complete self-rating forms and to cooperate with other study procedures.
  • I.Q. \< 70
  • Autistic disorder or more than mild autism spectrum disorder;
  • Psychosis that interferes with the child s capacity to understand and comply with study procedures
  • Unstable medical illness (e.g. severe asthma)
  • Medical illness that could cause the symptoms of BSD (e.g. multiple sclerosis, thyroid disease)
  • Pregnancy
  • Substance abuse within two months of the initial evaluation, since alcohol and abused substances interfere with interpretation of fMRI and cognitive task data.
  • NIMH IRP Employee family member
  • Adults with BD participating as individuals or as parents of at- risk children:
  • +127 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (22)

  • Geller B, Sun K, Zimerman B, Luby J, Frazier J, Williams M. Complex and rapid-cycling in bipolar children and adolescents: a preliminary study. J Affect Disord. 1995 Aug 18;34(4):259-68. doi: 10.1016/0165-0327(95)00023-g.

    PMID: 8550951BACKGROUND

  • Wozniak J, Biederman J, Kiely K, Ablon JS, Faraone SV, Mundy E, Mennin D. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):867-76. doi: 10.1097/00004583-199507000-00010.

    PMID: 7649957BACKGROUND

  • Faedda GL, Baldessarini RJ, Suppes T, Tondo L, Becker I, Lipschitz DS. Pediatric-onset bipolar disorder: a neglected clinical and public health problem. Harv Rev Psychiatry. 1995 Nov-Dec;3(4):171-95. doi: 10.3109/10673229509017185.

    PMID: 9384947BACKGROUND

  • Chen G, Taylor PA, Reynolds RC, Leibenluft E, Pine DS, Brotman MA, Pagliaccio D, Haller SP. BOLD Response is more than just magnitude: Improving detection sensitivity through capturing hemodynamic profiles. Neuroimage. 2023 Aug 15;277:120224. doi: 10.1016/j.neuroimage.2023.120224. Epub 2023 Jun 15.

    PMID: 37327955DERIVED

  • 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: 35794298DERIVED

  • 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: 34438022DERIVED

  • 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: 33479511DERIVED

  • 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: 33242544DERIVED

  • 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: 32138938DERIVED

  • Leibenluft E. Chronic irritability in children is not pediatric bipolar disorder: Implications for treatment. Bipolar Disord. 2020 Mar;22(2):195-196. doi: 10.1111/bdi.12881. Epub 2019 Dec 19. No abstract available.

    PMID: 31820531DERIVED

  • 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: 31330239DERIVED

  • 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: 31064595DERIVED

  • 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: 30851221DERIVED

  • 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: 30336704DERIVED

  • 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: 29083031DERIVED

  • 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: 28482689DERIVED

  • 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: 28103715DERIVED

  • 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: 27993231DERIVED

  • Tseng WL, Thomas LA, Harkins E, Stoddard J, Zarate CA Jr, Pine DS, Leibenluft E, Brotman MA. Functional connectivity during masked and unmasked face emotion processing in bipolar disorder. Psychiatry Res Neuroimaging. 2016 Dec 30;258:1-9. doi: 10.1016/j.pscychresns.2016.10.006. Epub 2016 Oct 24.

    PMID: 27814457DERIVED

  • 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: 26924633DERIVED

  • 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: 26892942DERIVED

  • 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: 26745832DERIVED

Related Links

MeSH Terms

Conditions

Bipolar DisorderMood Disorders

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMental Disorders

Study Officials

  • Ellen Leibenluft, M.D.

    National Institute of Mental Health (NIMH)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
OTHER
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 12, 2000

First Posted

August 14, 2000

Study Start

August 11, 2000

Last Updated

March 17, 2023

Record last verified: 2023-03-08

Data Sharing

IPD Sharing
Will not share

.We do not plan to make IDP available.

Locations

US(1)