The association between Major Depressive Disorder and premature death risk in hematologic and solid cancer: a longitudinal cohort study

  • Federica Sancassiani
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Elena Massa
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Carla Pibia
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Giulia Perda
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Laura Boe
    Department of Medical Sciences and Public Health, University of Cagliari, Italy , Italy.
  • Elena Fantozzi
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Giulia Cossu
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Giovanni Caocci
    Hematology and CTMO, Businco Hospital, ARNAS “G. Brotzu”, Cagliari, Italy.
  • Olga Mulas
    Hematology e CTMO, Businco Hospital, ARNAS “G. Brotzu”, Cagliari, Italy.
  • Emanuela Morelli
    Hematology and CTMO, Businco Hospital, ARNAS “G. Brotzu”, Cagliari, Italy.
  • Jutta Lindert
    University of Applied Sciences Emden/Leer, Emden, Germany.
  • Eleonora Lai
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Antonio Egidio Nardi
    Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil.
  • Mario Scartozzi
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.
  • Giorgio La Nasa
    Department of Medical Sciences and Public Health, University of Cagliari; Hematology and CTMO, Businco Hospital, ARNAS “G. Brotzu”, Cagliari, Italy.
  • Mauro Giovanni Carta
    Department of Medical Sciences and Public Health, University of Cagliari, Italy.


Background: the aim was to verify the association between Major Depressive Disorders (MDD) and the risk of premature death in people with oncological diseases, and to collect evidence about the causality of a possible association from a longitudinal perspective.

Design and Methods
: it is a cohort study lasting 9 months, involving people with solid or hematologic cancers. The assessment was conducted by an ad hoc form to collect socio-demographic and clinical-oncological data, the PHQ-9 to screen MDD (cut-off ≥10) and the SF-12 to evaluate HRQoL. Relative Risk (RR) of early death between MDD exposed and not-exposed and Kaplan-Meier survival were carried out.
Results: people exposed to MDD during the follow-up were 107/263 (40.7%). Among them, 36 deceased during the observation period. Overtime, having MDD and death’ occurrence showed a strong association (RR=2.15; 95% CI (1.10-4.20); χ²=5.224, p=0.0022), confirmed by Kaplan-Meier survival analysis (χ²=4.357, p=0.037). Among people who died, there was not any association between MDD, age, gender, HRQoL, cancer stage and site.

: the study confirms the association between MDD and early death in people with cancer. The absence of any association between the onset of MDD and advanced stage of cancer may suggest that it could be due to the consequences of MDD in worsening the clinical conditions related to cancer. The findings point out the relevance of MDD’ early detention among people with cancer.


Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015 22;386:743-800.

Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health 2013;34:119-38. DOI:

Carta MG, Aguglia E, Bocchetta A, et al. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemiol Ment Health 2010;6:94-100. DOI:

Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. Erratum in: JAMA Psychiatry 2015;72:736. Erratum in: JAMA Psychiatry 2015;72:1259JAMA Psychiatry 2015;72:334-41. DOI:

Machado MO, Veronese N, Sanches M, et al. The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Med 2018;16:112. DOI:

Scocco P, Idotta C, Mareschi T, et al. Do interpersonal events buffer or worsen depressive and grief related symptoms in people bereaved through suicide? Death Stud 2020:1-10. Online ahead of print. doi: 10.1080/07481187.2020.1855608 DOI:

Rackley S, Bostwick JM. Depression in medically ill patients. Psychiatr Clin North Am 2012;35:231-47. DOI:

Cuijpers P, Vogelzangs N, Twisk J, et al. Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses. Am J Psychiatry 2014;171:453-62. DOI:

Satin JR, Linden W, Phillips MJ. Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer 2009;115:5349-61. DOI:

Bortolato B, Hyphantis TN, Valpione S, et al. Depression in cancer: The many biobehavioral pathways driving tumor progression. Cancer Treat Rev 2017;52:58-70. DOI:

World Health Organization. WHO report on cancer: setting priorities, investing wisely and providing care for all. Geneva: World Health Organization; 2020. Available from:

Lutgendorf SK, Andersen BL. Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions. Am Psychol 2015;70:186-97. DOI:

Ostuzzi G, Matcham F, Dauchy S, et al. Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev 2018;4:CD011006. DOI:

van Dams R, Grogan T, Lee P, et al. Impact of health-related quality of life and prediagnosis risk of major depressive disorder on treatment choice for stage I lung cancer. JCO Clin Cancer Inform 2019;3:1-8. DOI:

Arrieta O, Angulo LP, Núñez-Valencia C, et al. Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol 2013;20:1941-8. DOI:

Mantovani G, Astara G, Lampis B, et al. Evaluation by multidimensional instruments of health-related quality of life of elderly cancer patients undergoing three different “psychosocial” treatment approaches. A randomized clinical trial. Support Care Cancer 1996;4:129-40. DOI:

La Nasa G, Caocci G, Morelli E, et al. Health related quality of life in patients with onco-hematological diseases. Clin Pract Epidemiol Ment Health 2020;16:174-9. DOI:

Zonderman AB, Costa PT Jr, McCrae RR. Depression as a risk for cancer morbidity and mortality in a nationally representative sample. JAMA 1989;262:1191-5. DOI:

Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst 2014;106:dju244. DOI:

Rizzo R, Piccinelli M, Mazzi MA, et al. The Personal Health Questionnaire: a new screening instrument for detection of ICD-10 depressive disorders in primary care. Psychol Med 2000;30:831-40. DOI:

Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA 1999;282:1737-44. DOI:

Apolone G, Mosconi P, Quattrociocchi L, et al. [Questionario sullo stato di salute SF-12 Versione Italiana].[in Italian]. Milano: Istituto di Ricerche Farmacologiche Mario Negri; 2001.

Ware J Jr, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220-33. DOI:

Krebber AM, Buffart LM, Kleijn G, et al. Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments. Psychooncology 2014;23:121-30. DOI:

Andersen BL, Rowland JH, Somerfield MR. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology Guideline adaptation. J Oncol Pract 2015;11:133-4. DOI:

Thekkumpurath P, Walker J, Butcher I, et al. Screening for major depression in cancer outpatients: the diagnostic accuracy of the 9-item patient health questionnaire. Cancer 2011;117:218-27. DOI:

Hartung TJ, Friedrich M, Johansen C, et al. The Hospital Anxiety and Depression Scale (HADS) and the 9-item Patient Health Questionnaire (PHQ-9) as screening instruments for depression in patients with cancer. Cancer 2017;123:4236-43. DOI:

Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry 2017;4:146-58. DOI:

Lloyd-Williams M, Shiels C, Taylor F, Dennis M. Depression–an independent predictor of early death in patients with advanced cancer. J Affect Disord 2009;113:127-32. DOI:

Pinquart M, Duberstein PR. Associations of social networks with cancer mortality: a meta-analysis. Crit Rev Oncol Hematol 2010;75:122-37. DOI:

Hartung TJ, Brähler E, Faller H, et al. The risk of being depressed is significantly higher in cancer patients than in the general population: Prevalence and severity of depressive symptoms across major cancer types. Eur J Cancer 2017;72:46-53. DOI:

Najjar S, Pearlman DM, Alper K, et al. Neuroinflammation and psychiatric illness. J Neuroinflammation 2013;10:43. DOI:

Moylan S, Maes M, Wray NR, Berk M. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry 2013;18:595-606. DOI:

Dantzer R, O'Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9:46-56. DOI:

Reiche EM, Nunes SO, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol 2004;5:617-25. DOI:

Seruga B, Zhang H, Bernstein LJ, Tannock IF. Cytokines and their relationship to the symptoms and outcome of cancer. Nat Rev Cancer 2008;8:887-99. DOI:

Miller GE, Chen E, Parker KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull 2011;137:959-97. DOI:

Zhang MF, Wen YS, Liu WY, et al. Effectiveness of mindfulness-based therapy for reducing anxiety and depression in patients with cancer: A meta-analysis. Medicine (Baltimore) 2015;94:e0897-0. DOI:

Galway K, Black A, Cantwell M, et al. Psychosocial interventions to improve quality of life and emotional wellbeing for recently diagnosed cancer patients. Cochrane Database Syst Rev 2012;11:CD007064. DOI:

Spencer JC, Wheeler SB. A systematic review of Motivational Interviewing interventions in cancer patients and survivors. Patient Educ Couns 2016;99:1099-105. DOI: