Have a personal or library account? Click to login
Exploring the Causal Relationships and Mediating Factors Between Mental Disorders and Hypertension: A Multivariable Mendelian Randomization Study Cover

Exploring the Causal Relationships and Mediating Factors Between Mental Disorders and Hypertension: A Multivariable Mendelian Randomization Study

Global Heart
Volume 20 (2025): Issue 1
By: Kunyan Li,  Chun Yin,  Hao Yang,  Zhichun Gao,  Wang Dong and  Jun Jin  
Open Access
|Oct 2025

References

  1. 1Wang C, Xing C, Li Z, Liu Y, Li Q, Wang Y, et al. Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension. Bioact Mater. 2022;8:494–504. DOI: 10.1016/j.bioactmat.2021.06.005
    Back to article
  2. 2Liu W, Huang X, Liu X, Ortega D, Chen L, Chen Z, et al. Uncontrolled hypertension associates with subclinical cerebrovascular health globally: A multimodal imaging study. Eur Radiol. 2021;31(4):2233–2241. DOI: 10.1007/s00330-020-07218-5
    Back to article
  3. 3Pereira M, Lunet N, Azevedo A, Barros H. Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries. J Hypertens. 2009;27(5):963–975. DOI: 10.1097/HJH.0b013e3283282f65
    Back to article
  4. 4Kidoguchi S, Sugano N, Tokudome G, Yokoo T, Yano Y, Hatake K, et al. New concept of onco-hypertension and future perspectives. Hypertension. 2021;77(1):16–27. DOI: 10.1161/HYPERTENSIONAHA.120.16044
    Back to article
  5. 5Wang C, Yuan Y, Zheng M, Pan A, Wang M, Zhao M, et al. Association of age of onset of hypertension with cardiovascular diseases and mortality. J Am Coll Cardiol. 2020;75(23):2921–2930. DOI: 10.1016/j.jacc.2020.04.038
    Back to article
  6. 6Barquera S, Campos-Nonato I, Hernández-Barrera L, Villalpando S, Rodríguez-Gilabert C, Durazo-Arvizú R, et al. Hypertension in Mexican adults: Results from the national health and nutrition survey 2006. Salud Publica Mex. 2010;52 Suppl 1: S63–71. DOI: 10.1590/S0036-36342010000700010
    Back to article
  7. 7Bijani M, Parvizi S, Dehghan A, Sedigh-Rahimabadi M, Rostami-Chijan M, Kazemi M, et al. Investigating the prevalence of hypertension and its associated risk factors in a population-based study: Fasa persian cohort data. BMC Cardiovasc Disord. 2020;20(1):503. DOI: 10.1186/s12872-020-01797-3
    Back to article
  8. 8Ventura HO, Lavie CJ. Impact of comorbidities in hypertension. Curr Opin Cardiol. 2016;31(4):374–375. DOI: 10.1097/HCO.0000000000000302
    Back to article
  9. 9GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the global burden of disease study 2017. Lancet. 2018;392(10159):1789–1858. DOI: 10.1016/S0140-6736(18)32279-7
    Back to article
  10. 10Lu Y, Wang Z, Georgakis MK, Lin H, Zheng L. Genetic liability to depression and risk of coronary artery disease, myocardial infarction, and other cardiovascular outcomes. J Am Heart Assoc. 2021;10(1): e017986. DOI: 10.1161/JAHA.120.017986
    Back to article
  11. 11Mushtaq M, Najam N. Depression, anxiety, stress and demographic determinants of hypertension disease. Pak J Med Sci. 2014;30(6):1293–1298. DOI: 10.12669/pjms.306.5433
    Back to article
  12. 12Patten SB, Williams JV, Lavorato DH, Campbell NR, Eliasziw M, Campbell TS. Major depression as a risk factor for high blood pressure: Epidemiologic evidence from a national longitudinal study. Psychosom Med. 2009;71(3):273–279. DOI: 10.1097/PSY.0b013e3181988e5f
    Back to article
  13. 13Wu EL, Chien IC, Lin CH, Chou YJ, Chou P. Increased risk of hypertension in patients with major depressive disorder: A population-based study. J Psychosom Res. 2012;73(3):169–174. DOI: 10.1016/j.jpsychores.2012.07.002
    Back to article
  14. 14Hildrum B, Mykletun A, Holmen J, Dahl AA. Effect of anxiety and depression on blood pressure: 11-year longitudinal population study. Br J Psychiatry. 2008;193(2):108–113. DOI: 10.1192/bjp.bp.107.045013
    Back to article
  15. 15Lenoir H, Lacombe JM, Dufouil C, Ducimetière P, Hanon O, Ritchie K, et al. Relationship between blood pressure and depression in the elderly. The three-city study. J Hypertens. 2008;26(9):1765–1772. DOI: 10.1097/HJH.0b013e3283088d1f
    Back to article
  16. 16Davies SJ, Ghahramani P, Jackson PR, Hippisley-Cox J, Yeo WW, Ramsay LE. Panic disorder, anxiety and depression in resistant hypertension--a case-control study. J Hypertens. 1997;15(10):1077–1082. DOI: 10.1097/00004872-199715100-00005
    Back to article
  17. 17Jeon SW, Chang Y, Lim SW, Cho J, Kim HN, Kim KB, et al. Bidirectional association between blood pressure and depressive symptoms in young and middle-age adults: A cohort study. Epidemiol Psychiatr Sci. 2020;29:e142. DOI: 10.1017/S2045796020000542
    Back to article
  18. 18Zhang X, Li C. Major depressive disorder increased the risk of hypertension: A mendelian randomization study. J Affect Disord. 2024;355:184–189. DOI: 10.1016/j.jad.2024.03.144
    Back to article
  19. 19Xu Z, Wu X, Xiao C, Zhang W, Yan P, Yang C, et al. Observational and genetic analyses of the bidirectional relationship between depression and hypertension. J Affect Disord. 2024;348:62–69. DOI: 10.1016/j.jad.2023.12.028
    Back to article
  20. 20Cai L, Liu Y, He L. Investigating genetic causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being. Gen Psychiatr. 2022;35(5):e100877. DOI: 10.1136/gpsych-2022-100877
    Back to article
  21. 21Sanderson E. Multivariable mendelian randomization and mediation. Cold Spring Harb Perspect Med. 2021;11(2). DOI: 10.1101/cshperspect.a038984
    Back to article
  22. 22Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: The Strobe-MR statement. JAMA. 2021;326(16):1614–1621. DOI: 10.1001/jama.2021.18236
    Back to article
  23. 23Howard DM, Adams MJ, Shirali M, Clarke TK, Marioni RE, Davies G, et al. Genome-wide association study of depression phenotypes in UK biobank identifies variants in excitatory synaptic pathways. Nat Commun. 2018;9(1):1470. DOI: 10.1038/s41467-018-03819-3
    Back to article
  24. 24Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44(9):981–990. DOI: 10.1038/ng.2383
    Back to article
  25. 25Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable mendelian randomisation analysis. PLoS Med. 2020;17(3):e1003062. DOI: 10.1371/journal.pmed.1003062
    Back to article
  26. 26Dennis JK, Sealock JM, Straub P, Lee YH, Hucks D, Actkins K, et al. Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease. Genome Med. 2021;13(1):6. DOI: 10.1186/s13073-020-00820-8
    Back to article
  27. 27Davyson E, Shen X, Gadd DA, Bernabeu E, Hillary RF, McCartney DL, et al. Metabolomic investigation of major depressive disorder identifies a potentially causal association with polyunsaturated fatty acids. Biol Psychiatry. 2023;94(8):630–639. DOI: 10.1016/j.biopsych.2023.01.027
    Back to article
  28. 28Carter AR, Sanderson E, Hammerton G, Richmond RC, Davey Smith G, Heron J, et al. Mendelian randomisation for mediation analysis: Current methods and challenges for implementation. Eur J Epidemiol. 2021;36(5):465–478. DOI: 10.1007/s10654-021-00757-1
    Back to article
  29. 29Meng L, Chen D, Yang Y, Zheng Y, Hui R. Depression increases the risk of hypertension incidence: A meta-analysis of prospective cohort studies. J Hypertens. 2012;30(5):842–851. DOI: 10.1097/HJH.0b013e32835080b7
    Back to article
  30. 30Qiu W, Cai A, Li L, Feng Y. Association of depression trajectories and subsequent hypertension and cardiovascular disease: Findings from the charls cohort. J Hypertens. 2024;42(3):432–440. DOI: 10.1097/HJH.0000000000003609
    Back to article
  31. 31Adamis D, Ball C. Physical morbidity in elderly psychiatric inpatients: Prevalence and possible relations between the major mental disorders and physical illness. Int J Geriatr Psychiatry. 2000;15(3):248–253. DOI: 10.1002/(SICI)1099-1166(200003)15:3<;248::AID-GPS102>3.0.CO;2-L
    Back to article
  32. 32Rantanen AT, Korkeila JJA, Löyttyniemi ES, Saxén UKM, Korhonen PE. Awareness of hypertension and depressive symptoms: A cross-sectional study in a primary care population. Scand J Prim Health Care. 2018;36(3):323–328. DOI: 10.1080/02813432.2018.1499588
    Back to article
  33. 33Gan Q, Yu R, Lian Z, Yuan Y, Li Y, Zheng L. Unraveling the link between hypertension and depression in older adults: A meta-analysis. Front Public Health. 2023;11:1302341. DOI: 10.3389/fpubh.2023.1302341
    Back to article
  34. 34Long J, Duan G, Tian W, Wang L, Su P, Zhang W, et al. Hypertension and risk of depression in the elderly: A meta-analysis of prospective cohort studies. J Hum Hypertens. 2015;29(8):478–482. DOI: 10.1038/jhh.2014.112
    Back to article
  35. 35Reiff M, Schwartz S, Northridge M. Relationship of depressive symptoms to hypertension in a household survey in Harlem. Psychosom Med. 2001;63(5):711–721. DOI: 10.1097/00006842-200109000-00002
    Back to article
  36. 36Pan Y, Cai W, Cheng Q, Dong W, An T, Yan J. Association between anxiety and hypertension: A systematic review and meta-analysis of epidemiological studies. Neuropsychiatr Dis Treat. 2015;11:1121–1130. DOI: 10.2147/NDT.S77710
    Back to article
  37. 37Johnson HM. Anxiety and hypertension: Is there a link? A literature review of the comorbidity relationship between anxiety and hypertension. Curr Hypertens Rep. 2019;21(9):66. DOI: 10.1007/s11906-019-0972-5
    Back to article
  38. 38Qi H, Wen FY, Xie YY, Liu XH, Li BX, Peng WJ, et al. Associations between depressive, anxiety, stress symptoms and elevated blood pressure: Findings from the CHCN-BTH cohort study and a two-sample Mendelian randomization analysis. J Affect Disord. 2023;341:176–184. DOI: 10.1016/j.jad.2023.08.086
    Back to article
  39. 39Lim LF, Solmi M, Cortese S. Association between anxiety and hypertension in adults: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2021;131:96–119. DOI: 10.1016/j.neubiorev.2021.08.031
    Back to article
  40. 40Shah RM, Doshi S, Shah S, Patel S, Li A, Diamond JA. Impacts of anxiety and depression on clinical hypertension in low-income us adults. High Blood Press Cardiovasc Prev. 2023;30(4):337–342. DOI: 10.1007/s40292-023-00584-3
    Back to article
  41. 41Duman H, Duman H, Puşuroğlu M, Yılmaz AS. Anxiety disorders and depression are associated with resistant hypertension. Adv Clin Exp Med. 2024;33(2):111–118. DOI: 10.17219/acem/166304
    Back to article
  42. 42Davies SJ, Ghahramani P, Jackson PR, Noble TW, Hardy PG, Hippisley-Cox J, et al. Association of panic disorder and panic attacks with hypertension. Am J Med. 1999;107(4):310–316. DOI: 10.1016/S0002-9343(99)00237-5
    Back to article
  43. 43Bajkó Z, Szekeres CC, Kovács KR, Csapó K, Molnár S, Soltész P, et al. Anxiety, depression and autonomic nervous system dysfunction in hypertension. J Neurol Sci. 2012;317(1–2):112–116. DOI: 10.1016/j.jns.2012.02.014
    Back to article
  44. 44Mocking RJ, Ruhé HG, Assies J, Lok A, Koeter MW, Visser I, et al. Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression. Psychoneuroendocrinology. 2013;38(9):1607–1617. DOI: 10.1016/j.psyneuen.2013.01.013
    Back to article
  45. 45Virdis A, Giannarelli C, Neves MF, Taddei S, Ghiadoni L. Cigarette smoking and hypertension. Curr Pharm Des. 2010;16(23):2518–2525. DOI: 10.2174/138161210792062920
    Back to article
  46. 46Gelber RP, Gaziano JM, Manson JE, Buring JE, Sesso HD. A prospective study of body mass index and the risk of developing hypertension in men. Am J Hypertens. 2007;20(4):370–377. DOI: 10.1016/j.amjhyper.2006.10.011
    Back to article
  47. 47Salameh AB, Hyassat D, Suhail A, Makahleh Z, Khader Y, El-Khateeb M, et al. The prevalence of hypertension and its progression among patients with type 2 diabetes in Jordan. Ann Med Surg (Lond). 2022;73:103162. DOI: 10.1016/j.amsu.2021.103162
    Back to article
  48. 48Saasita PK, Senoga S, Muhongya K, Agaba DC, Migisha R. High prevalence of uncontrolled hypertension among patients with type 2 diabetes mellitus: A hospital-based cross-sectional study in Southwestern Uganda. Pan Afr Med J. 2021;39:142. DOI: 10.11604/pamj.2021.39.142.28620
    Back to article
  49. 49Jia G, Sowers JR. Hypertension in diabetes: An update of basic mechanisms and clinical disease. Hypertension. 2021;78(5):1197–1205. DOI: 10.1161/HYPERTENSIONAHA.121.17981
    Back to article
  50. 50Semenkovich K, Brown ME, Svrakic DM, Lustman PJ. Depression in type 2 diabetes mellitus: Prevalence, impact, and treatment. Drugs. 2015;75(6):577–587. DOI: 10.1007/s40265-015-0347-4
    Back to article
  51. 51Fiore V, Marci M, Poggi A, Giagulli VA, Licchelli B, Iacoviello M, et al. The association between diabetes and depression: A very disabling condition. Endocrine. 2015;48(1):14–24. DOI: 10.1007/s12020-014-0323-x
    Back to article
  52. 52Fluharty M, Taylor AE, Grabski M, Munafò MR. The association of cigarette smoking with depression and anxiety: A systematic review. Nicotine Tob Res. 2017;19(1):3–13. DOI: 10.1093/ntr/ntw140
    Back to article
DOI: https://doi.org/10.5334/gh.1483 | Journal eISSN: 2211-8179
Journal RSS Feed
Language: English
Submitted on: Nov 28, 2024
Accepted on: Sep 26, 2025
Published on: Oct 14, 2025
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year
Keywords:
mental disorders,
depression,
hypertension,
Multivariable Mendelian randomization,
mediation analysis

© 2025 Kunyan Li, Chun Yin, Hao Yang, Zhichun Gao, Wang Dong, Jun Jin, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.

Previous articleVolume 20 (2025): Issue 1Next article