Back to top Open menu arrow
Download Reprints
Sections
METHODS RESULTS DISCUSSION Article Information Clinical Points
The Journal of Clinical Psychiatry The Journal of Clinical Psychiatry

The Journal of
Clinical Psychiatry
Access icon

Original Research Childhood and Adolescent Mental Health July 1, 2024

Controlled Study of Metabolic Syndrome Among Offspring of Parents With Bipolar Disorder

Nidhi P. Kulkarni, MSc; Mikaela K. Dimick, PhD; Kody G. Kennedy, PhD; David A. Axelson, MD; Dara J. Sakolsky, MD, PhD; Rasim S. Diler, MD; Danella M. Hafeman, MD, PhD; Tina R. Goldstein, PhD; Kelly J. Monk, BSN, RN; Fangzi Liao, MS; John A. Merranko, MA; Boris Birmaher, MD; Benjamin I. Goldstein, MD, PhD

J Clin Psychiatry 2024;85(3):23m15058

Abstract

Objectives: Bipolar disorder (BD) is highly heritable and associated with increased rates of metabolic syndrome (MetS). However, little is known about MetS in offspring of parents with BD. We therefore examined this topic in the Pittsburgh Bipolar Offspring Study cohort.

Methods: Participants included 199 parents (n = 116 BD, diagnosed using DSM-IV; n = 83 non-BD) and 330 offspring (mean age 19.9 ± 5.3 years), including 198 high-risk offspring of parents with BD (n = 80 affected with a mood disorder) and 132 control offspring. We defined MetS and its components using International Diabetes Federation (IDF) guidelines (primary) and National Cholesterol Education Program (NCEP) guidelines (secondary). Multivariable analyses controlled for age and socioeconomic status in offspring. Sensitivity analyses controlled for psychotropic medications.

Results: There was higher prevalence of MetS in parents with BD as compared to controls. NCEP-defined MetS was significantly more prevalent among affected high-risk offspring (16.3%) and controls (15.2%) vs unaffected high-risk offspring (6.0%; χ2 = 6.54, P = .04). There was greater mean number of MetS components (IDF: 1.7 ± 1.1; NCEP: 1.4 ± 1.0) among affected high-risk offspring vs unaffected high-risk offspring (IDF: 1.2 ± 1.0; NCEP: 1.0 ± 1.0) and controls (IDF: 1.3 ± 1.2; NCEP: 1.1 ± 1.1; IDF: H[2] = 10.26, P = .006; NCEP: H[2] = 9.18, P = .01). Most findings became nonsignificant in multivariable analyses. Some between-group results became nonsignificant after controlling for second-generation antipsychotics.

Conclusions: This preliminary study found increased risk of MetS among affected high-risk offspring, which may be attributable to socioeconomic status. Prospective studies may determine timing of MetS onset in relation to mood disorder onset, and the role of socioeconomic status in moderating this association.

J Clin Psychiatry 2024;85(3):23m15058

Author affiliations are listed at the end of this article.

Continue Reading...

Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Purchase PDF for $40

Members enjoy free PDF downloads on all articles. Join today

  1. Clemente AS, Diniz BS, Nicolato R, et al. Bipolar disorder prevalence: a systematic review and meta-analysis of the literature. Braz J Psychiatry. 2015;37(2):155–161. PubMed CrossRef
  2. Goldstein BI, Birmaher B, Carlson GA, et al. The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: knowledge to date and directions for future research. Bipolar Disord. 2017;19(7):524–543. PubMed CrossRef
  3. Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241–251. PubMed CrossRef
  4. Goldstein BI, Baune BT, Bond DJ, et al. Call to action regarding the vascular-bipolar link: a report from the vascular task force of the international society for bipolar disorders. Bipolar Disord. 2020;22(5):440–460. PubMed CrossRef
  5. McRae L, O’Donnell S, Loukine L, et al. Report summary - Mood and Anxiety Disorders in Canada, 2016. Health Promot Chronic Dis Prev Can. 2016;36(12):314–315.
  6. Goldstein BI, Schaffer A, Wang S, et al. Excessive and premature new-onset cardiovascular disease among adults with bipolar disorder in the US NESARC cohort. J Clin Psychiatry. 2015;76(2):163–169. PubMed CrossRef
  7. Goldstein BI, Carnethon MR, Matthews KA, et al. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2015;132(10):965–986. PubMed
  8. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1459–1544. PubMed CrossRef
  9. Hoang U, Stewart R, Goldacre MJ. Mortality after hospital discharge for people with schizophrenia or bipolar disorder: retrospective study of linked English hospital episode statistics, 1999–2006. BMJ. 2011;343:d5422. PubMed CrossRef
  10. Westman J, Hällgren J, Wahlbeck K, et al. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ Open. 2013;3(4):e002373. PubMed CrossRef
  11. Laursen TM, Mortensen PB, Maccabe JH, et al. Cardiovascular drug use and mortality in patients with schizophrenia or bipolar disorder: a Danish population-based study. Psychol Med. 2014;44(8):1625–1637. PubMed CrossRef
  12. Fiedorowicz JG, Palagummi NM, Forman-Hoffman VL, et al. Elevated prevalence of obesity, metabolic syndrome, and cardiovascular risk factors in bipolar disorder. Ann Clin Psychiatry. 2008;20(3):131–137. PubMed CrossRef
  13. Islam AH, Metcalfe AWS, MacIntosh BJ, et al. Greater body mass index is associated with reduced frontal cortical volumes among adolescents with bipolar disorder. J Psychiatry Neurosci. 2018;43(2):120–130. PubMed CrossRef
  14. Kennedy KG, Islam AH, Grigorian A, et al. Elevated lipids are associated with reduced regional brain structure in youth with bipolar disorder. Acta Psychiatr Scand. 2021;143(6):513–525. PubMed CrossRef
  15. Naiberg MR, Hatch JK, Selkirk B, et al. Retinal photography: a window into the cardiovascular-brain link in adolescent bipolar disorder. J Affect Disord. 2017;218:227–237. PubMed CrossRef
  16. Goldstein BI, Blanco C, He JP, et al. Correlates of overweight and obesity among adolescents with bipolar disorder in the National Comorbidity Survey-Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2016;55(12):1020–1026. PubMed CrossRef
  17. Shapiro J, Mindra S, Timmins V, et al. Controlled study of obesity among adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2017;27(1):95–100. PubMed
  18. Goldstein BI, Collinger KA, Lotrich F, et al. Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders. J Child Adolesc Psychopharmacol. 2011;21(5):479–484. PubMed CrossRef
  19. Shapiro LR, Kennedy KG, Dimick MK, et al. Elevated atherogenic lipid profile in youth with bipolar disorder during euthymia and hypomanic/mixed but not depressive states. J Psychosom Res. 2022;156:110763. PubMed CrossRef
  20. McElroy SL, Keck PE Jr. Metabolic syndrome in bipolar disorder: a review with a focus on bipolar depression. J Clin Psychiatry. 2014;75(1):46–61. PubMed CrossRef
  21. Vancampfort D, Vansteelandt K, Correll CU, et al. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry. 2013;170(3):265–274. PubMed CrossRef
  22. Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome–a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006;23(5):469–480.
  23. Li C, Birmaher B, Rooks B, et al. High prevalence of metabolic syndrome among adolescents and young adults with bipolar disorder. J Clin Psychiatry. 2019;80(4):18m12422. PubMed CrossRef
  24. Reisinger C, Nkeh-Chungag BN, Fredriksen PM, et al. The prevalence of pediatric metabolic syndrome–a critical look on the discrepancies between definitions and its clinical importance. Int J Obes (Lond). 2021;45(1):12–24. PubMed
  25. Mattsson N, Rönnemaa T, Juonala M, et al. The prevalence of the metabolic syndrome in young adults. The cardiovascular risk in Young Finns Study. J Intern Med. 2007;261(2):159–169. PubMed CrossRef
  26. Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. Am J Med Genet C Semin Med Genet. 2003;123C(1):48–58. PubMed CrossRef
  27. Birmaher B, Axelson D, Goldstein B, et al. Psychiatric disorders in preschool offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring Study (BIOS). Am J Psychiatry. 2010;167(3):321–330. PubMed CrossRef
  28. Huang MH, Chen MH, Huang KL, et al. Increased risk of type 2 diabetes among the siblings of patients with schizophrenia. CNS Spectr. 2019;24(4):453–459. PubMed CrossRef
  29. van Welie H, Derks EM, Verweij KH, et al. The prevalence of diabetes mellitus is increased in relatives of patients with a non-affective psychotic disorder. Schizophr Res. 2013;143(2–3):354–357. PubMed CrossRef
  30. Fernandez-Egea E, Bernardo M, Parellada E, et al. Glucose abnormalities in the siblings of people with schizophrenia. Schizophr Res. 2008;103(1–3):110–113. PubMed CrossRef
  31. Mannie ZN, Williams C, Diesch J, et al. Cardiovascular and metabolic risk profile in young people at familial risk of depression. Br J Psychiatry. 2013;203(1):18–23. PubMed CrossRef
  32. Coello K, Kjærstad HL, Stanislaus S, et al. Thirty-year cardiovascular risk score in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives. Aust N Z J Psychiatry. 2019;53(7):651–662. PubMed CrossRef
  33. Tsao WY, Hsu JW, Huang KL, et al. Risk of cardiometabolic diseases among siblings of patients with bipolar disorder. J Affect Disord. 2019;253:171–175. PubMed CrossRef
  34. Baptista T, Serrano A, Uzcátegui E, et al. The metabolic syndrome and its constituting variables in atypical antipsychotic-treated subjects: comparison with other drug treatments, drug-free psychiatric patients, first-degree relatives and the general population in Venezuela. Schizophr Res. 2011;126(1–3):93–102. PubMed CrossRef
  35. Sobczak S, Honig A, Christophe A, et al. Lower high-density lipoprotein cholesterol and increased omega-6 polyunsaturated fatty acids in first-degree relatives of bipolar patients. Psychol Med. 2004;34(1):103–112. PubMed CrossRef
  36. Baptista T, Sandia I, Fernandez E, et al. Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder. Braz J Psychiatry. 2015;37(2):106–112. PubMed CrossRef
  37. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003;107(3):499–511. PubMed CrossRef
  38. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836–843. PubMed CrossRef
  39. Birmaher B, Axelson D, Monk K, et al. Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder the Pittsburgh bipolar offspring study. Arch Gen Psychiatry. 2009;66(3):287–296. PubMed CrossRef
  40. Spitzer RL, Williams JBW, Gibbon M, et al. The structured clinical interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry. 1992;49(8):624–629. PubMed CrossRef
  41. Kaufman J, Birmaher B, Brent D, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36(7):980–988. PubMed CrossRef
  42. Andreasen NC, Endicott J, Spitzer RL, et al. The family history method using diagnostic criteria: reliability and validity. Arch Gen Psychiatry. 1977;34(10):1229–1235. PubMed CrossRef
  43. Axelson D, Birmaher B, Strober M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006;63(10):1139–1148. PubMed CrossRef
  44. Hollingshead AA. Four-factor index of social status. Yale University; 1975.
  45. Leckman JF, Sholomskas D, Thompson WD, et al. Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982;39(8):879–883. PubMed CrossRef
  46. Friedman GD, Cutter GR, Donahue RP, et al. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41(11):1105–1116. PubMed CrossRef
  47. Burke GL, Savage PJ, Sprafka JM, et al. Relation of risk factor levels in young adulthood to parental history of disease. The CARDIA study. Circulation. 1991;84(3):1176–1187. PubMed CrossRef
  48. Jacobs DR Jr, Hahn LP, Haskell WL, et al. Validity and reliability of short physical activity history: cardia and the Minnesota Heart Health Program. J Cardiopulm Rehabil. 1989;9(11):448–459. PubMed CrossRef
  49. Sidney S, Jacobs DR Jr, Haskell WL, et al. Comparison of two methods of assessing physical activity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Epidemiol. 1991;133(12):1231–1245. PubMed CrossRef
  50. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth Rep on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 suppl 4th Report):555–576. PubMed
  51. Krebs NF, Himes JH, Jacobson D, et al. Assessment of child and adolescent overweight and obesity. Pediatrics. 2007;120(suppl 4):S193–S228. PubMed CrossRef
  52. Lee K, Valeria B, Kochman C, et al. Self-assessment of height, weight, and sexual maturation: validity in overweight children and adolescents. J Adolesc Health. 2006;39(3):346–352. PubMed CrossRef
  53. Lee S, Bacha F, Gungor N, et al. Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers. J Pediatr. 2008;152(2):177–184. PubMed CrossRef
  54. Zimmet P, Alberti KGM, Kaufman F, et al. The metabolic syndrome in children and adolescents–an IDF consensus report. Pediatr Diabetes. 2007;8(5):299–306. PubMed CrossRef
  55. National Cholesterol Education Program NCEP Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III. Third report of the national cholesterol education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106(25):3143–3421. PubMed
  56. DeBoer MD. Assessing and managing the metabolic syndrome in children and adolescents. Nutrients. 2019;11(8):1788. PubMed
  57. Bitew ZW, Alemu A, Tenaw Z, et al. Prevalence of metabolic syndrome among children and adolescents in high-income countries: a systematic review and meta-analysis of observational studies. Biomed Res Int. 2021;2021. PubMed
  58. Bitew ZW, Alemu A, Ayele EG, et al. Metabolic syndrome among children and adolescents in low and middle income countries: a systematic review and meta-analysis. Diabetol Metab Syndr. 2020;12:93. PubMed CrossRef
  59. Goldstein BI, Lotrich F, Axelson DA, et al. Inflammatory markers among adolescents and young adults with bipolar spectrum disorders. J Clin Psychiatry. 2015;76(11):1556–1563. PubMed CrossRef
  60. Martin DJ, Ul-Haq Z, Nicholl BI, et al. Cardiometabolic disease and features of depression and bipolar disorder: population-based, cross-sectional study. Br J Psychiatry. 2016;208(4):343–351. PubMed CrossRef
  61. Silarova B, Giltay EJ, Van Reedt Dortland A, et al. Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls. J Psychosom Res. 2015;78(4):391–398. PubMed CrossRef
  62. Lee YB, Kim H, Lee J, et al. Bipolar disorder and the risk of cardiometabolic diseases, heart failure, and all-cause mortality: a population-based matched cohort study in South Korea. Sci Rep. 2024;14(1):1932. PubMed
  63. Birkenaes AB, Søgaard AJ, Engh JA, et al. Sociodemographic characteristics and cardiovascular risk factors in patients with severe mental disorders compared with the general population. J Clin Psychiatry. 2006;67(3):425–433. PubMed CrossRef
  64. Blanquet M, Legrand A, Pélissier A, et al. Socio-economics status and metabolic syndrome: a meta-analysis. Diabetes Metab Syndr. 2019;13(3):1805–1812. PubMed CrossRef
  65. Bahrani R, Chan YM, Khor GL, et al. The relationship between metabolic syndrome and its components with socio-economic status among adolescents in Shiraz, Southern Iran. Southeast Asian J Trop Med Public Health. 2016;47(2):263–276. PubMed
  66. Mirhosseini NZ, Yusoff NAM, Shahar S, et al. Prevalence of the metabolic syndrome and its influencing factors among adolescent girls in Mashhad, Iran. Asia Pac J Clin Nutr. 2009;18(1):131–136. PubMed
  67. Macpherson M, de Groh M, Loukine L, et al. Prevalence of metabolic syndrome and its risk factors in Canadian children and adolescents: Canadian Health Measures Survey Cycle 1 (2007–2009) and Cycle 2 (2009–2011). Health Promot Chronic Dis Prev Can. 2016;36(2):32–40. PubMed CrossRef
  68. Gustafsson PE, Persson M, Hammarstrom A. Life course origins of the metabolic syndrome in middle-aged women and men: the role of socioeconomic status and metabolic risk factors in adolescence and early adulthood. Ann Epidemiol. 2011;21(2):103–110. PubMed CrossRef
  69. Taylor V, MacQueen G. Associations between bipolar disorder and metabolic syndrome: a review. J Clin Psychiatry. 2006;67(7):1034–1041. PubMed CrossRef
  70. Dubath C, Gholam-Rezaee M, Sjaarda J, et al. Socio-economic position as a moderator of cardiometabolic outcomes in patients receiving psychotropic treatment associated with weight gain: results from a prospective 12-month inception cohort study and a large population-based cohort. Transl Psychiatry 2021;11(1):360. PubMed CrossRef
  71. Tamashiro KLK. Metabolic syndrome: links to social stress and socioeconomic status. Ann N Y Acad Sci. 2011;1231(1):46–55. PubMed CrossRef
  72. Suglia SF, Koenen KC, Boynton-Jarrett R, et al. Childhood and adolescent adversity and cardiometabolic outcomes: a scientific statement from the American heart association. Circulation. 2018;137(5):e15–e28. PubMed CrossRef
  73. Su S, Jimenez MP, Roberts CTF, et al. The role of adverse childhood experiences in cardiovascular disease risk: a review with emphasis on plausible mechanisms. Curr Cardiol Rep. 2015;17(10):88. PubMed CrossRef
  74. Mogi M. Hypertension management to prevent dementia. Hypertens Res. 2022;45(4):573–575. PubMed CrossRef
  75. Fernández-Jiménez R, Real C. Optimizing blood pressure components for a healthy brain: the holy grail in blood pressure management. J Am Coll Cardiol. 2022;79(14):1336–1339. PubMed
  76. Harrison JK, Van Der Wardt V, Conroy SP, et al. New horizons: the management of hypertension in people with dementia. Age Ageing. 2016;45(6):740–746. PubMed CrossRef
  77. Peters R, Xu Y, Fitzgerald O, et al. Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis. Eur Heart J. 2022;43(48):4980–4990. PubMed CrossRef
Purchase PDF for $40

Members enjoy free PDF downloads on all articles. Join today

Save Save

Share Share

Cite Cite

Vol 85 • 2024 • Number 3

Read the Current Issue

Editorial

Focus on Women’s Mental Health: Twenty Years and Counting

Original Research

Esmethadone in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants

Commentary

Can Our Collective Experiences As Clinicians Improve Mental Health Care?

Original Research

Prescription Opioid Use Disorder in US Adults Reporting Prescription Opioid Use

Original Research

Symptomatic Disorders Comorbid with Borderline Personality Disorder Over Time

Original Research

Aripiprazole Lauroxil Initiation Regimens
View current Issue

Celebrating
85 Years

Read the Journal of Clinical Psychiatry

Subscribe to read
more articles

Subscribe