Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder

Neuropsychopharmacology volume 48, pages 954–962 (2023)Cite this article

Subjects

Abstract

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Accelerated DNAm GrimAge and GrimAge in BD groups.

Similar content being viewed by others

References

  1. Carvalho AF, Firth J, Vieta E. Bipolar disorder. N Engl J Med. 2020;383:58–66.

    Article  CAS  PubMed  Google Scholar 

  2. Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68:241–51.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sylvia LG, Montana RE, Deckersbach T, Thase ME, Tohen M, Reilly-Harrington N, et al. Poor quality of life and functioning in bipolar disorder. Int J Bipolar Disord. 2017;5:10.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Roshanaei-Moghaddam B, Katon W. Premature mortality from general medical illnesses among persons with bipolar disorder: a review. Psychiatr Serv. 2009;60:147–56.

    Article  PubMed  Google Scholar 

  5. Hayes JF, Miles J, Walters K, King M, Osborn DPJ. A systematic review and meta-analysis of premature mortality in bipolar affective disorder. Acta Psychiatr Scand. 2015;131:417–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bauer M, Andreassen OA, Geddes JR, Kessing LV, Lewitzka U, Schulze TG, et al. Areas of uncertainties and unmet needs in bipolar disorders: clinical and research perspectives. Lancet Psychiatry. 2018;5:930–9.

    Article  PubMed  Google Scholar 

  7. Hansen PS, Laursen MF, Grøntved S, Straszek SPV, Licht RW, Nielsen RE. Increasing mortality gap for patients diagnosed with bipolar disorder—a nationwide study with 20 years follow-up. Bipolar Disord. 2019;21:270–5.

    Article  Google Scholar 

  8. Dome P, Rihmer Z, Gonda X. Suicide risk in bipolar disorder: a brief review. Med. 2019;55:403.

    Google Scholar 

  9. Jokinen J, Talb M, Feychting M, Ahlbom A, Ljung R, Ljung R. Life expectancy after the first suicide attempt. Acta Psych Scand. 2018;137:287–95.

    Article  CAS  Google Scholar 

  10. Huang YC, Wang LJ, Tseng PT, Hung CG, Lin PY. Leukocyte telomere length in patients with bipolar disorder: an updated meta-analysis and subgroup analysis by mood status. Psychiatry Res. 2018;270:41–49.

    Article  CAS  PubMed  Google Scholar 

  11. Birkenæs V, Elvsåshagen T, Westlye LT, Høegh MC, Haram M, Werner MCF, et al. Telomeres are shorter and associated with number of suicide attempts in affective disorders. J Affect Disord. 2021;295:1032–9.

    Article  PubMed  Google Scholar 

  12. Martinez D, Lavebratt C, Millischer V, de Jesus R, de Paula V, Pires T, et al. Shorter telomere length and suicidal ideation in familial bipolar disorder. PLoS One. 2022;17:e0275999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev. 2013;84:49–57.

    Article  PubMed  Google Scholar 

  14. Hackett JA, Surani MA. DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc B. 2013;368:20110328.

    Article  Google Scholar 

  15. Jazwinski SM, Kim S. Examination of the dimensions of biological age. Front Genet. 2019;10:263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018;19:371–84.

    Article  CAS  PubMed  Google Scholar 

  17. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49:359–67.

    Article  CAS  PubMed  Google Scholar 

  18. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Han LK, Aghajani M, Clark SL, Chan RF, Hattab MW, Shabalin AA, et al. Epigenetic aging in major depressive disorder. Am J Psychiatry. 2018;175:774–82.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Grodstein F, Lemos B, Yu L, Klein HU, Iatrou A, Buchman AS, et al. The association of epigenetic clocks in brain tissue with brain pathologies and common aging phenotypes. Neurobiol Dis. 2021;157:105428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fries GR, Bauer IE, Scaini G, Valvassori SS, Walls-Bass C, Soares JC, et al. Accelerated hippocampal biological aging in bipolar disorder. Bipolar Disord. 2020;22:498–507.

    Article  CAS  PubMed  Google Scholar 

  22. Fries GR, Bauer IE, Scaini G, Wu MJ, Kazimi IF, Valvassori SS, et al. Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder. Transl Psychiatry 2017;7:1283.

    Article  PubMed  PubMed Central  Google Scholar 

  23. McCrory C, Fiorito G, Hernandez B, Polidoro S, O’Halloran AM, Hever A, et al. GrimAge outperforms other epigenetic clocks in the prediction of age-related clinical phenotypes and all-cause mortality. J Gerontol A Biol Sci Med Sci. 2021;76:741–9.

    Article  PubMed  Google Scholar 

  24. Hillary RF, Stevenson AJ, Cox SR, McCartney DL, Harris SE, Seeboth A, et al. An epigenetic predictor of death captures multi-modal measures of brain health. Mol Psychiatry. 2021;26:3806–16.

    Article  PubMed  Google Scholar 

  25. Lima CNC, Suchting R, Scaini G, Cuellar VA, del Favero-Campbell A, Walss-Bass C, et al. Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder. Eur Neuropsychopharmacol. 2022;62:10–21.

    Article  CAS  PubMed  Google Scholar 

  26. Okazaki S, Otsuka I, Horai T, Hirata T, Takahashi M, Ueno Y, et al. Accelerated extrinsic epigenetic aging and increased natural killer cells in blood of suicide completers. Prog Neuropsychopharmacol Biol Psych. 2020;98:109805.

    Article  CAS  Google Scholar 

  27. Jokinen J, Andersson P, Chatzittofis A, Savard J, Rask-Andersen M, Åsberg M, et al. Accelerated epigenetic aging in suicide attempters uninfluenced by high intent-to-die and choice of lethal methods. Transl Psychiatry. 2022;12:224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429–35.

    Article  CAS  PubMed  Google Scholar 

  29. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9.

    Article  CAS  PubMed  Google Scholar 

  30. Rocha NB, Brokke SS, Landrø NI, Haaland VØ. Cognitive control in suicide ideators and suicide attempters. Front Psychol. 2020;11:595673.

    Article  Google Scholar 

  31. Shaffer JJ, Johnson CP, Long JD, Fiederowicz JG, Christensen GE, Wemmie JA, et al. Relationship altered between functional T1ρ and BOLD signals in bipolar disorder. Brain Behav. 2017;7:802.

    Article  Google Scholar 

  32. Shaffer JJ, Willour V, Fiedorowicz JG, Christensen GE, Long JD, Johnson CP, et al. Distinct patterns of altered quantitative T1ρ and functional BOLD response associated with history of suicide attempts in bipolar disorder. Brain Imaging Behav. 2022;16:820–33.

    Article  PubMed  Google Scholar 

  33. Shaffer JJ, Johnson CP, Fiedorowicz JG, Christensen GE, Wemmie JA, Magnotta VA. Impaired sensory processing measured by functional MRI in Bipolar disorder manic and depressed mood states. Brain Imaging Behav. 2018;12:837–47.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Fiedorowicz JG, Prossin AR, Johnson CP, Christensen GE, Magnotta VA, Wemmie JA. Peripheral inflammation during abnormal mood states in bipolar I disorder. J Affect Disord. 2015;187:172–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Johnson CP, Follmer RL, Oguz I, Warren LA, Christensen GE, Fiedorowicz JG, et al. Quantitative T1ρ mapping links the cerebellum and lithium use in bipolar disorder. Mol Psychiatry. 2015;20:149.

    Article  CAS  PubMed  Google Scholar 

  36. Johnson CP, Follmer RL, Oguz I, Warren LA, Christensen GE, Fiedorowicz JG, et al. Brain abnormalities in bipolar disorder detected by quantitative T1ρ mapping. Mol Psychiatry. 2015;20:201–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Johnson CP, Christensen GE, Fiedorowicz JG, Mani M, Shaffer JJ, Magnotta VA, et al. Alterations of the cerebellum and basal ganglia in bipolar disorder mood states detected by quantitative T1ρ mapping. Bipolar Disord. 2018;20:381–90.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266–77.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):11980.

    Google Scholar 

  40. Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinform. 2012;13:86.

    Article  Google Scholar 

  42. Bollepalli S, Korhonen T, Kaprio J, Anders S, Ollikainen M. EpiSmokEr: A robust classifier to determine smoking status from DNA methylation data. Epigenomics. 2019;11:1469–86.

    Article  CAS  PubMed  Google Scholar 

  43. Elliott HR, Tillin T, McArdle WL, Ho K, Duggirala A, Frayling TM, et al. Differences in smoking associated DNA methylation patterns in south Asians and Europeans. Clin Epi. 2014;6:4.

    Article  Google Scholar 

  44. Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging. 11:303–27.

  45. R Core Team. R: a language and environment for statistical computing. 2022. https://www.r-project.org. Accessed 1 Nov 2022.

  46. Wickham H. ggplot2: elegant graphics for data analysis. Springer New York: New York, NY; 2016.

  47. Wickham H, Girlich M. tidyr: Tidy Messy Data. 2022. https://cran.r-project.org/package=tidyr. Accessed 1 Nov 2022.

  48. Wickham H, François R, Henry L, Müller K. dplyr: a grammar of data manipulation. 2022. https://cran.r-project.org/package=dplyr. Accessed 1 Nov 2022.

  49. Bache SM, Wickham H. magrittr: a forward-pipe operator for R. 2022. https://cran.r-project.org/package=magrittr. Accessed 1 Nov 2022.

  50. Kassambara A. ggpubr: “ggplot2” based publication ready plots. 2020. https://cran.r-project.org/package=ggpubr. Accessed 1 Nov 2022.

  51. IBM Corp. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY; 2021.

  52. Esang M, Ahmed S. A closer look at substance use and suicide. Am J Psychiatry Residents’ J. 2018;13:6–8.

    Article  Google Scholar 

  53. Melhem NM, Porta G, Oquendo MA, Zelazny J, Keilp JG, Iyengar S, et al. Severity and variability of depression symptoms predicting suicide attempt in high-risk individuals. JAMA Psychiatry. 2019;76:603–13.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Zatti C, Guimarães LSP, Soibelman M, Semensato MR, Bastos AG, Calegaro VC, et al. The association between traumatic experiences and suicide attempt in patients treated at the Hospital de Pronto Socorro in Porto Alegre, Brazil. Trends Psychiatry Psychother. 2020;42:64–73.

    Article  PubMed  Google Scholar 

  55. Näher AF, Rummel-Kluge C, Hegerl U. Associations of suicide rates with socioeconomic status and social isolation: findings from longitudinal register and census data. Front Psychiatry. 2020;10:898.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Fiorito G, McCrory C, Robinson O, Carmeli C, Rosales CO, Zhang Y, et al. Socioeconomic position, lifestyle habits and biomarkers of aging: a multi-cohort analysis. Aging. 2019;11:2045–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Luo A, Jung J, Longley M, Rosoff DB, Chalet K, Muench C, et al. Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2. Neuropsychopharmacology. 2019;45:327–36.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Jovanovic T, Vance LA, Cross D, Knight AK, Kilaru V, Michopoulos V, et al. Exposure to violence accelerates epigenetic aging in children. Nat Sci Rep. 2017;7:8962.

    Google Scholar 

  59. Rosen AD, Robertson KD, Hlady RA, Muench C, Lee J, Philibert R, et al. DNA methylation age is accelerated in alcohol dependence. Transl Psychiatry. 2018;8:182.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bøstrand SMK, Vaher K, de Nooij L, Harris MA, Cole JH, Cox SR, et al. Associations between alcohol use and accelerated biological ageing. Addict Biol. 2022;27:e13100.

    Article  PubMed  Google Scholar 

  61. Li S, Nguyen TL, Wong EM, Dugué PA, Dite GS, Armstrong NJ, et al. Genetic and environmental causes of variation in epigenetic aging across the lifespan. Clin Epigenet. 2020;12:1–12.

    Article  Google Scholar 

  62. Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality in bipolar disorder. Ann Clin Psychiatry. 2011;23:40–47.

    PubMed  PubMed Central  Google Scholar 

  63. Wu MK, Wang HY, Chen YW, Lin PY, Wu CK, Tseng PT. Significantly higher prevalence rate of asthma and bipolar disorder co-morbidity: a meta-analysis and review under PRISMA guidelines. Medicines. 2016;95:e3217.

    Google Scholar 

  64. McIntyre RS, Konarski JZ, Misener VL, Kennedy SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry. 2005;17:83–93.

    Article  PubMed  Google Scholar 

  65. Chakrabarti S. Thyroid functions and bipolar affective disorder. J Thyroid Res. 2011;2011:306367.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Franceschi C, Ostan R, Mariotti S, Monti D, Vitale G. The aging thyroid: a reappraisal within the geroscience integrated perspective. Endocr Rev. 2019;40:1250–70.

    PubMed  Google Scholar 

  67. Yang Y, Yuan L, Yang M, Du Q, Wang L, Zhou K, et al. Aberrant methylation of aging-related genes in asthma. Front Mol Biosci. 2021;8:655285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Grant CD, Jafari N, Hou L, Li Y, Stewart JD, Zhang G, et al. A longitudinal study of DNA methylation as a potential mediator of age-related diabetes risk. GeroScience 2017;39:475–789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Herman AB, Occean JR, Sen P. Epigenetic dysregulation in cardiovascular aging and disease. J Cardiovasc Aging. 2021;1:10.

    PubMed  PubMed Central  Google Scholar 

  70. Vaughan DE, Rai R, Khan SS, Eren M, Ghosh AK. PAI-1 is a marker and a mediator of senescence. Arterioscler Thromb Vasc Biol. 2017;37:1446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost. 2005;3:1879–83.

    Article  CAS  PubMed  Google Scholar 

  72. Jiang H, Chen S, Li C, Lu N, Yue Y, Yin Y, et al. The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment. Transl Psychiatry. 2017;7:e1079.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gerenu G, Martisova E, Ferrero H, Carracedo M, Rantamäki T, Ramirez MJ, et al. Modulation of BDNF cleavage by plasminogen-activator inhibitor-1 contributes to Alzheimer’s neuropathology and cognitive deficits. Biochim Biophys Acta Mol Basis Dis. 2017;1863:991–1001.

    Article  CAS  PubMed  Google Scholar 

  74. Goldstein BI, Young LT. Toward clinically applicable biomarkers in bipolar disorder: focus on BDNF, inflammatory markers, and endothelial function. Curr Psychiatry Rep. 2013;15:425.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Fusar-Poli L, Aguglia A, Amerio A, Orsolini L, Salvi V, Seragini G, et al. Peripheral BDNF levels in psychiatric patients with and without a history of suicide attempt: a systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110342.

    Article  PubMed  Google Scholar 

  76. Misztak P, Pańczyszyn-Trzewik P, Nowak G, Sowa-Kućma M. Epigenetic marks and their relationship with BDNF in the brain of suicide victims. PLoS One. 2020;15:e0239335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Erbay L, Karhdağ R, Oruç M, Çiğremiş Y, Celbiş O. Association of BDNF/TRBB and NGF/TRKA levels in postmortem brain with major depression and suicide. Psychiatr Danub. 2021;33:491.

    Article  CAS  PubMed  Google Scholar 

  78. Iikuni N, Lam QLK, Lu L, Matarese G, La Cava A. Leptin and Inflammation. Curr Immunol Rev. 2008;4:70–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T, Sánchez-Margalet V. Role of leptin in inflammation and vice versa. Int J Mol Sci. 2020;21:1–24.

    Article  Google Scholar 

  80. Lengvenyte A, Aouizerate B, Aubin V, Loftus J, Marlinge E, Belzeaux R, et al. Violent suicide attempt history in elderly patients with bipolar disorder: The role of sex, abdominal obesity, and verbal memory: Results from the FACE-BD cohort (FondaMental Advanced center of Expertise for Bipolar Disorders). J Affect Disord. 2022;296:265–76.

    Article  PubMed  Google Scholar 

  81. da Graça Cantarelli M, Nardin P, Buffon A, Eidt MC, Godoy LA, Fernandes BS, et al. Serum triglycerides, but not cholesterol or leptin, are decreased in suicide attempters with mood disorders. J Affect Disord. 2015;172:403–9.

    Article  PubMed  Google Scholar 

  82. Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Serum leptin and cholesterol values in violent and non-violent suicide attempters. Psychiatry Res. 2008;158:87–91.

    Article  CAS  PubMed  Google Scholar 

  83. Fiedorowicz JG, Solomon DA, Endicott J, Leon AC, Chunshan MA, Rice J, et al. Manic/hypomanic symptom burden predicts cardiovascular mortality with bipolar disorder in the collaborative depression study. Psychosom Med. 2009;71:598–606.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Calkin CV, Ruzickova M, Uher R, Hajek T, Slaney CM, Garnham JS, et al. Insulin resistance and outcome in bipolar disorder. Br J Psychiatry. 2015;206:52–57.

    Article  PubMed  Google Scholar 

  85. Sodhi SK, Linder J, Chenard CA, Miller DD, Haynes WG, Fiedorowicz JG. Evidence for accelerated vascular aging in bipolar disorder. J Psychosom Res. 2012;73:175–9.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Fahy GM, Brooke RT, Watson JP, et al. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 2019;18:e13028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Fitzgerald KN, Hodges R, Hanes D, Stack E, Cheishvili D, Szyf M, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging 2021;13:9419–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Sarai SK, Mekala HM, Lippmann S. Lithium suicide prevention: a brief review and reminder. Innov Clin Neurosci. 2018;15:30–32.

    PubMed  PubMed Central  Google Scholar 

  89. Salarda EM, Zhao NO, Lima CNNC, Fries GR. Mini-review: The anti-aging effects of lithium in bipolar disorder. Neurosci Lett. 2021;759:136051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Spano L, Etain B, Meyrel M, Hennion V, Gross G, Laplanche JL, et al. Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging. Transl Psychiatry. 2022;12:135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Nannini DR, Joyce BT, Zheng Y, Gao T, Wang J, Liu L, et al. Alcohol consumption and epigenetic age acceleration in young adults. Aging. 2023;15:371–95.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Zindler T, Frieling H, Fliedner L, Veer I, Neyazi A, Awasthi S, et al. How alcohol makes the epigenetic clock tick faster and the clock reversing effect of abstinence. Addict Biol. 2022;27:e13198.

    Article  CAS  PubMed  Google Scholar 

  93. Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM. Naïve T cell maintenance and function in human aging. J Immunol. 2015;194:4073–80.

    Article  CAS  PubMed  Google Scholar 

  94. Pfister G, Weiskopf D, Lazuardi L, Kovaiou RD, Cioca DP, Keller M, et al. Naive T cells in the elderly: are they still there? Ann NY Acad Sci. 2006;1067:152–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Reagents and sample hybridization in the replication cohort were provided by the Iowa Institute of Human Genetics Genomics Division (IIHG). We would like to thank Hsiang Wen for sample collection and management for the replication cohort. We would like to thank the study participants in both cohorts for their willingness to participate in the study. This study was supported by the National Institute of Mental Health (NIMH, K01 MH121580 to GRF), the American Foundation for Suicide Prevention (YIG-0-066-20 to GRF), and the Baszucki Research Foundation (GRF). Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School at UTHealth. This study was also supported by an EHSRC Career Enhancement award and an EHSRC Pilot grant (NIH P30 ES005605) awarded to MEG, and an Iowa Neuroscience Institute Research Program of Excellence grant with philanthropy from the Roy J. Carver Charitable Trust. Research reported in this publication for the University of Iowa was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537) and the National Institute of Mental Health (NIMH R01MH125838 to VAM and JAW). APD is supported by a 2020 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the American Foundation for Suicide Prevention, or the Baszucki Research Foundation.

Author information

Author notes

  1. These authors contributed equally: Camila N. de Carvalho Lima, Emese H.C. Kovács.

  2. These authors jointly supervised this work: Marie E. Gaine, Gabriel R. Fries.

Authors and Affiliations

  1. Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA

    Camila N. C. Lima, Salahudeen Mirza, Alexandra Del Favero-Campbell, Joao Quevedo & Gabriel R. Fries

  2. Department of Neuroscience and Pharmacology, The University of Iowa, 51 Newton Rd, 52242, Iowa City, IA, USA

    Emese H. C. Kovács

  3. Institute of Child Development, University of Minnesota, 51 E River Rd, 55455, Minneapolis, MN, USA

    Salahudeen Mirza

  4. Center for the Study and Prevention of Suicide, Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA

    Alexandre Paim Diaz

  5. Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA

    Joao Quevedo, Jair C. Soares & Gabriel R. Fries

  6. Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 6767 Bertner Ave, 77030, Houston, TX, USA

    Joao Quevedo, Jair C. Soares & Gabriel R. Fries

  7. Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, 180 South Grand Ave, 52242, Iowa City, IA, USA

    Benney M. R. Argue & Marie E. Gaine

  8. Department of Radiology, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA

    Jenny Gringer Richards & Vincent A. Magnotta

  9. Department of Psychiatry, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA

    Aislinn Williams, John A. Wemmie & Vincent A. Magnotta

  10. Iowa Neuroscience Institute, The University of Iowa, 169 Newton Rd, 52242, Iowa City, IA, USA

    Aislinn Williams & Marie E. Gaine

  11. University of Ottawa Brain and Mind Research Institute, Ottawa Hospital Research Institute, 501 Smyth, K1H 8L6, Ottawa, ON, Canada

    Jess G. Fiedorowicz

  12. Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin, 77030, Houston, TX, USA

    Gabriel R. Fries

Authors
  1. Camila N. C. Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emese H. C. Kovács
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Salahudeen Mirza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandra Del Favero-Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexandre Paim Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joao Quevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Benney M. R. Argue
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jenny Gringer Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aislinn Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. John A. Wemmie
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Vincent A. Magnotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jess G. Fiedorowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jair C. Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Marie E. Gaine
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Gabriel R. Fries
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Design and conceptualization of the study: CNCL, EHCK, MEG, and GRF. Sample collection and recruitment: EHCK, BMRA, JFR, AW, JAW, VAM, JGF, APD, JQ, and JCS. Data generation, processing, and statistical analyses: CNCL, EHCK, SM, ADFC, and APD. Scientific discussion and interpretation of results: CNCL, EHCK, SM, AW, JAW, VAM, APD, JQ, JCS, JGF, MEG, and GRF. Wrote the manuscript: CNCL, EHCK, SM, MEG, and GRF.

Corresponding author

Correspondence to Gabriel R. Fries.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lima, C.N.C., Kovács, E.H.C., Mirza, S. et al. Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder. Neuropsychopharmacol. 48, 954–962 (2023). https://doi.org/10.1038/s41386-023-01557-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41386-023-01557-9

This article is cited by

Search

Advanced search

Quick links