Evaluation of the Genetics of Bipolar Disorder

Bipolar Genetics: A Collaborative Study

This study looks to identify genes that may affect a person's chances of developing bipolar disorder (BP) and related conditions.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder

Detailed Description

Bipolar affective disorder is a severe, heritable condition affecting about one percent of

the population. The mode of inheritance is poorly understood and probably involves multiple loci of small to moderate effect. In this project, we use genetic mapping and sequencing methods to identify genetic markers and variations that contribute to the risk of bipolar disorder. Individuals diagnosed with bipolar disorder are studied, along with their relatives. Phenotypic information obtained from clinical interviews and family history is correlated with genotypic information obtained from genetic marker and sequencing methods. The goal is to identify genes involved in bipolar disorder and related conditions so that better methods of diagnosis, treatment, and prevention can be developed.

• Study Type: Observational
• Enrollment (Estimated): 6000

Contacts and Locations

• Study Contact: Name: Emily Besancon; Phone Number: (866) 644-4363; Email: emily.besancon@nih.gov
• Study Contact Backup: Name: Francis J McMahon, M.D.; Phone Number: (301) 451-4455; Email: mcmahonf@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

community samples and clinical samples

Description

• INCLUSION CRITERIA:

Age > 18 yr

Able to provide informed consent

Bipolar disorder or related conditions not attributable to substance abuse, neurological disease; or a 1st or 2nd degree relative of an enrolled participant. Related conditions are defined as those found more often among relatives of people with bipolar disorder or which have been shown to be genetically correlated with bipolar disorder through molecular genetic studies. These include major depression, schizophrenia, panic disorder, and attention deficit hyperactivity disorder.

Able to safely provide a blood or saliva sample

EXCLUSION CRITERIA:

Active alcohol or substance abuse.

NIMH employees/staff and their immediate family members will be excluded from the study per NIMH policy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy Volunteers; Healthy volunteers
Patients; Patients with bipolar disorder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of bipolar disorder or related mental illness by direct interview	Psychiatric diagnosis is based on systematic review of established signs and symptoms, using an instrument designed to elicit retrospective information of known reliability, supplemented with information from family informants, any medical records, and by dimensional symptom measures.	Diagnosis is established primarily at the initial study visit. Participants who consent to recontact are re-evaluated when they or family informants report events that could lead to a revised diagnosis.

Collaborators and Investigators

• Sponsor: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Francis J McMahon, M.D., National Institute of Mental Health (NIMH)

Publications and helpful links

General Publications

• Pisanu C, Congiu D, Costa M, Chillotti C, Ardau R, Severino G, Angius A, Heilbronner U, Hou L, McMahon FJ, Schulze TG, Del Zompo M, Squassina A. Convergent analysis of genome-wide genotyping and transcriptomic data suggests association of zinc finger genes with lithium response in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2018 Oct;177(7):658-664. doi: 10.1002/ajmg.b.32663. Epub 2018 Oct 14.
• Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N, Ardau R, Arias B, Backlund L, Banzato CEM, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Birner A, Brichant-Petitjean C, Bui ET, Cervantes P, Chen GB, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cousins DA, Cruceanu C, Czerski PM, Dantas CR, Dayer A, Etain B, Falkai P, Forstner AJ, Frisen L, Fullerton JM, Gard S, Garnham JS, Goes FS, Grof P, Gruber O, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jamain S, Jimenez E, Kahn JP, Kassem L, Kittel-Schneider S, Kliwicki S, Konig B, Kusumi I, Lackner N, Laje G, Landen M, Lavebratt C, Leboyer M, Leckband SG, Jaramillo CAL, MacQueen G, Manchia M, Martinsson L, Mattheisen M, McCarthy MJ, McElroy SL, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nothen MM, Osby U, Ozaki N, Perlis RH, Pfennig A, Reich-Erkelenz D, Rouleau GA, Schofield PR, Schubert KO, Schweizer BW, Seemuller F, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Smoller JW, Squassina A, Stamm T, Stopkova P, Tighe SK, Tortorella A, Turecki G, Volkert J, Witt S, Wright A, Young LT, Zandi PP, Potash JB, DePaulo JR, Bauer M, Reininghaus EZ, Novak T, Aubry JM, Maj M, Baune BT, Mitchell PB, Vieta E, Frye MA, Rybakowski JK, Kuo PH, Kato T, Grigoroiu-Serbanescu M, Reif A, Del Zompo M, Bellivier F, Schalling M, Wray NR, Kelsoe JR, Alda M, Rietschel M, McMahon FJ, Schulze TG. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet. 2016 Mar 12;387(10023):1085-1093. doi: 10.1016/S0140-6736(16)00143-4. Epub 2016 Jan 22.
• International Consortium on Lithium Genetics (ConLi+Gen); Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Heilbronner U, Degenhardt F, Tekola-Ayele F, Hsu YH, Shekhtman T, Adli M, Akula N, Akiyama K, Ardau R, Arias B, Aubry JM, Backlund L, Bhattacharjee AK, Bellivier F, Benabarre A, Bengesser S, Biernacka JM, Birner A, Brichant-Petitjean C, Cervantes P, Chen HC, Chillotti C, Cichon S, Cruceanu C, Czerski PM, Dalkner N, Dayer A, Del Zompo M, DePaulo JR, Etain B, Falkai P, Forstner AJ, Frisen L, Frye MA, Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jamain S, Jimenez E, Kahn JP, Kassem L, Kuo PH, Kato T, Kelsoe J, Kittel-Schneider S, Kliwicki S, Konig B, Kusumi I, Laje G, Landen M, Lavebratt C, Leboyer M, Leckband SG, Tortorella A, Manchia M, Martinsson L, McCarthy MJ, McElroy S, Colom F, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nothen MM, Novak T, O'Donovan C, Ozaki N, Osby U, Pfennig A, Potash JB, Reif A, Reininghaus E, Rouleau GA, Rybakowski JK, Schalling M, Schofield PR, Schweizer BW, Severino G, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Maj M, Turecki G, Vieta E, Volkert J, Witt S, Wright A, Zandi PP, Mitchell PB, Bauer M, Alda M, Rietschel M, McMahon FJ, Schulze TG, Baune BT. Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study. JAMA Psychiatry. 2018 Jan 1;75(1):65-74. doi: 10.1001/jamapsychiatry.2017.3433.
• Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M, Heilbronner U, Degenhardt F, Tekola-Ayele F, Hsu YH, Shekhtman T, Adli M, Akula N, Akiyama K, Ardau R, Arias B, Aubry JM, Backlund L, Bhattacharjee AK, Bellivier F, Benabarre A, Bengesser S, Biernacka JM, Birner A, Brichant-Petitjean C, Cervantes P, Chen HC, Chillotti C, Cichon S, Cruceanu C, Czerski PM, Dalkner N, Dayer A, Del Zompo M, DePaulo JR, Etain B, Jamain S, Falkai P, Forstner AJ, Frisen L, Frye MA, Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jimenez E, Kahn JP, Kassem L, Kuo PH, Kato T, Kelsoe JR, Kittel-Schneider S, Kliwicki S, Konig B, Kusumi I, Laje G, Landen M, Lavebratt C, Leboyer M, Leckband SG, Tortorella A, Manchia M, Martinsson L, McCarthy MJ, McElroy SL, Colom F, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nothen MM, Novak T, O'Donovan C, Ozaki N, Osby U, Pfennig A, Potash JB, Reif A; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Reininghaus E, Rouleau GA, Rybakowski JK, Schalling M, Schofield PR, Schweizer BW, Severino G, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Maj M, Turecki G, Vieta E, Veeh J, Witt SH, Wright A, Zandi PP, Mitchell PB, Bauer M, Alda M, Rietschel M, McMahon FJ, Schulze TG, Baune BT. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Mol Psychiatry. 2021 Jun;26(6):2457-2470. doi: 10.1038/s41380-020-0689-5. Epub 2020 Mar 16.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 1994

Study Registration Dates

• First Submitted: November 3, 1999
• First Submitted That Met QC Criteria: November 3, 1999
• First Posted (Estimated): November 4, 1999

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: August 16, 2023

More Information

Terms related to this study

• Keywords: Depression; Affective Disorder; Natural History; Bipolar Disorder; Panic Disorder; Major Depression; Genetic Polymorphisms; Genome-Wide Scan
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: 800083; 80-M-0083

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No