Association of Posttraumatic Stress and Depressive Symptoms With Mortality in Women

Andrea L Roberts, Laura D Kubzansky, Lori B Chibnik, Eric B Rimm, Karestan C Koenen, Andrea L Roberts, Laura D Kubzansky, Lori B Chibnik, Eric B Rimm, Karestan C Koenen

Abstract

Importance: Consistent evidence has found associations between posttraumatic stress disorder (PTSD) and increased risk of chronic disease and greater prevalence of health risk factors. However, the association between PTSD and all-cause mortality has not been thoroughly investigated in civilians.

Objective: To investigate the association between PTSD symptoms, with or without comorbid depressive symptoms, and risk of death.

Design, setting, and participants: This prospective cohort study was conducted using data on female US nurses in the Nurses' Health Study II followed up from 2008 to 2017. Women who responded to a 2008 questionnaire querying PTSD and depressive symptoms were included. Data were analyzed from September 2018 to November 2020.

Exposures: Symptoms of PTSD, measured using the short screening scale for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) PTSD, and depression symptoms, measured using the Center for Epidemiologic Studies Depression Scale-10 in 2008.

Main outcomes and measures: All-cause mortality was determined via National Death Index, US Postal Service, or report of participant's family. The hypothesis being tested was formulated after data collection. Trauma exposure and PTSD symptoms were jointly coded as no trauma exposure (reference), trauma and no PTSD symptoms, 1 to 3 PTSD symptoms (subclinical), 4 to 5 PTSD symptoms (moderate), and 6 to 7 PTSD symptoms (high).

Results: Among 51 602 women (50 137 [97.2%] White individuals), the mean (range) age was 53.3 (43-64) years at study baseline in 2008. PTSD and probable depression were comorbid; of 4019 women with high PTSD symptoms, 2093 women (52.1%) had probable depression, while of 10 105 women with no trauma exposure, 1215 women (12.0%) had probable depression. Women with high PTSD symptoms and probable depression were at nearly 4-fold greater risk of death compared with women with no trauma exposure and no depression (hazard ratio [HR], 3.80; 95% CI, 2.65-5.45; P < .001). After adjustment for health factors, women with these conditions had a more than 3-fold increased risk (HR, 3.11; 95% CI, 2.16-4.47, P < .001). Women with subclinical PTSD symptoms without probable depression had increased risk of death compared with women with no trauma exposure and no depression (HR, 1.43; 95% CI, 1.06-1.93; P = .02). Among 7565 women with PTSD symptoms and probable depression, 109 deaths (1.4%) occurred for which we obtained cause of death information, compared with 124 such deaths (0.6% ) among 22 215 women with no depression or PTSD symptoms. Women with PTSD symptoms and probable depression, compared with women with no PTSD or depression, had higher rates of death from cardiovascular disease (17 women [0.22%] vs 11 women [0.05%]; P < .001), diabetes (4 women [0.05%] vs 0 women; P < .001), unintentional injury (7 women [0.09%] vs 7 women [0.03%]; P = .03), suicide (9 women [0.12%] vs 1 woman [<0.01%]; P < .001), and other causes of death (14 women [0.19%] vs 17 women [0.08%]; P = .01).

Conclusions and relevance: These findings suggest that at midlife, women with high PTSD symptoms and co-occurring probable depression are at increased risk of death compared with women without these disorders. Treatment of PTSD and depression in women with symptoms of both disorders and efforts to improve their health behaviors may reduce their increased risk of mortality.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Roberts reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Kubzansky reported receiving grants from the NIH and the US Department of Defense during the conduct of the study. Dr Koenen reported receiving grants from the NIH and the US Department of Defense during the conduct of the study. No other disclosures were reported.

References

    1. Roberts AL, Agnew-Blais JC, Spiegelman D, et al. . Posttraumatic stress disorder and incidence of type 2 diabetes mellitus in a sample of women: a 22-year longitudinal study. JAMA Psychiatry. 2015;72(3):203-210. doi:10.1001/jamapsychiatry.2014.2632
    1. Sumner JA, Kubzansky LD, Roberts AL, et al. . Post-traumatic stress disorder symptoms and risk of hypertension over 22 years in a large cohort of younger and middle-aged women. Psychol Med. 2016;46(15):3105-3116. doi:10.1017/S0033291716001914
    1. Sumner JA, Kubzansky LD, Elkind MS, et al. . Trauma exposure and posttraumatic stress disorder symptoms predict onset of cardiovascular events in women. Circulation. 2015;132(4):251-259. doi:10.1161/CIRCULATIONAHA.114.014492
    1. Vaccarino V, Goldberg J, Rooks C, et al. . Post-traumatic stress disorder and incidence of coronary heart disease: a twin study. J Am Coll Cardiol. 2013;62(11):970-978. doi:10.1016/j.jacc.2013.04.085
    1. Lohr JB, Palmer BW, Eidt CA, et al. . Is post-traumatic stress disorder associated with premature senescence? A review of the literature. Am J Geriatr Psychiatry. 2015;23(7):709-725. doi:10.1016/j.jagp.2015.04.001
    1. Kubzansky LD, Bordelois P, Jun HJ, et al. . The weight of traumatic stress: a prospective study of posttraumatic stress disorder symptoms and weight status in women. JAMA Psychiatry. 2014;71(1):44-51. doi:10.1001/jamapsychiatry.2013.2798
    1. Rosenbaum S, Stubbs B, Ward PB, Steel Z, Lederman O, Vancampfort D. The prevalence and risk of metabolic syndrome and its components among people with posttraumatic stress disorder: a systematic review and meta-analysis. Metabolism. 2015;64(8):926-933. doi:10.1016/j.metabol.2015.04.009
    1. Dedert EA, Calhoun PS, Watkins LL, Sherwood A, Beckham JC. Posttraumatic stress disorder, cardiovascular, and metabolic disease: a review of the evidence. Ann Behav Med. 2010;39(1):61-78. doi:10.1007/s12160-010-9165-9
    1. Pace TW, Heim CM. A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities. Brain Behav Immun. 2011;25(1):6-13. doi:10.1016/j.bbi.2010.10.003
    1. Griffin GD, Charron D, Al-Daccak R. Post-traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis. Clin Transl Immunology. 2014;3(11):e27. doi:10.1038/cti.2014.26
    1. Sumner JA, Chen Q, Roberts AL, et al. . Cross-sectional and longitudinal associations of chronic posttraumatic stress disorder with inflammatory and endothelial function markers in women. Biol Psychiatry. 2017;82(12):875-884. doi:10.1016/j.biopsych.2017.06.020
    1. Speer K, Upton D, Semple S, McKune A. Systemic low-grade inflammation in post-traumatic stress disorder: a systematic review. J Inflamm Res. 2018;11:111-121. doi:10.2147/JIR.S155903
    1. Kobayashi I, Boarts JM, Delahanty DL. Polysomnographically measured sleep abnormalities in PTSD: a meta-analytic review. Psychophysiology. 2007;44(4):660-669. doi:10.1111/j.1469-8986.2007.537.x
    1. Wolf EJ, Logue MW, Morrison FG, et al. . Posttraumatic psychopathology and the pace of the epigenetic clock: a longitudinal investigation. Psychol Med. 2019;49(5):791-800. doi:10.1017/S0033291718001411
    1. Colpani V, Baena CP, Jaspers L, et al. . Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis. Eur J Epidemiol. 2018;33(9):831-845. doi:10.1007/s10654-018-0374-z
    1. Boscarino JA. Posttraumatic stress disorder and mortality among U.S. Army veterans 30 years after military service. Ann Epidemiol. 2006;16(4):248-256. doi:10.1016/j.annepidem.2005.03.009
    1. Bullman TA, Kang HK. Posttraumatic stress disorder and the risk of traumatic deaths among Vietnam veterans. J Nerv Ment Dis. 1994;182(11):604-610. doi:10.1097/00005053-199411000-00002
    1. Ahmadi N, Hajsadeghi F, Mirshkarlo HB, Budoff M, Yehuda R, Ebrahimi R. Post-traumatic stress disorder, coronary atherosclerosis, and mortality. Am J Cardiol. 2011;108(1):29-33. doi:10.1016/j.amjcard.2011.02.340
    1. Flood AM, Boyle SH, Calhoun PS, et al. . Prospective study of externalizing and internalizing subtypes of posttraumatic stress disorder and their relationship to mortality among Vietnam veterans. Compr Psychiatry. 2010;51(3):236-242. doi:10.1016/j.comppsych.2009.08.002
    1. Drescher KD, Rosen CS, Burling TA, Foy DW. Causes of death among male veterans who received residential treatment for PTSD. J Trauma Stress. 2003;16(6):535-543. doi:10.1023/B:JOTS.0000004076.62793.79
    1. Xue Y, Taub PR, Iqbal N, et al. . Cardiac biomarkers, mortality, and post-traumatic stress disorder in military veterans. Am J Cardiol. 2012;109(8):1215-1218. doi:10.1016/j.amjcard.2011.11.063
    1. Kimbrell T, Pyne JM, Kunik ME, et al. . The impact of Purple Heart commendation and PTSD on mortality rates in older veterans. Depress Anxiety. 2011;28(12):1086-1090. doi:10.1002/da.20850
    1. Zohar J, Fostick L; Israeli Consortium on PTSD . Mortality rates between treated post-traumatic stress disorder Israeli male veterans compared to non-diagnosed veterans. Eur Neuropsychopharmacol. 2014;24(1):117-124. doi:10.1016/j.euroneuro.2013.10.009
    1. Harvard Medical School National Comorbidity Survey (NCS): NCS-R appendix tables: table 1: lifetime prevalence of DSM-IV/WMH-CIDI disorders by sex and cohort. Accessed September 25, 2020.
    1. Breslau N, Chilcoat HD, Kessler RC, Peterson EL, Lucia VC. Vulnerability to assaultive violence: further specification of the sex difference in post-traumatic stress disorder. Psychol Med. 1999;29(4):813-821. doi:10.1017/S0033291799008612
    1. Ditlevsen DN, Elklit A. Gender, trauma type, and PTSD prevalence: a re-analysis of 18 nordic convenience samples. Ann Gen Psychiatry. 2012;11(1):26-26. doi:10.1186/1744-859X-11-26
    1. Gradus JL, Antonsen S, Svensson E, Lash TL, Resick PA, Hansen JG. Trauma, comorbidity, and mortality following diagnoses of severe stress and adjustment disorders: a nationwide cohort study. Am J Epidemiol. 2015;182(5):451-458. doi:10.1093/aje/kwv066
    1. Rytwinski NK, Scur MD, Feeny NC, Youngstrom EA. The co-occurrence of major depressive disorder among individuals with posttraumatic stress disorder: a meta-analysis. J Trauma Stress. 2013;26(3):299-309. doi:10.1002/jts.21814
    1. Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry. 2017;4(2):146-158. doi:10.1016/S2215-0366(16)30263-2
    1. Bracke P, Delaruelle K, Dereuddre R, Van de Velde S. Depression in women and men, cumulative disadvantage and gender inequality in 29 European countries. Soc Sci Med. 2020;113354. doi:10.1016/j.socscimed.2020.113354
    1. Fluharty 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
    1. Pan A, Sun Q, Czernichow S, et al. . Bidirectional association between depression and obesity in middle-aged and older women. Int J Obes (Lond). 2012;36(4):595-602. doi:10.1038/ijo.2011.111
    1. Cuijpers P, Smit F. Excess mortality in depression: a meta-analysis of community studies. J Affect Disord. 2002;72(3):227-236. doi:10.1016/S0165-0327(01)00413-X
    1. Harris EC, Barraclough B. Excess mortality of mental disorder. Br J Psychiatry. 1998;173:11-53. doi:10.1192/bjp.173.1.11
    1. Penninx BW, Geerlings SW, Deeg DJ, van Eijk JT, van Tilburg W, Beekman AT. Minor and major depression and the risk of death in older persons. Arch Gen Psychiatry. 1999;56(10):889-895. doi:10.1001/archpsyc.56.10.889
    1. Van den Akker M, Schuurman A, Ensinck K, Buntinx F. Depression as a risk factor for total mortality in the community: a meta-analysis. Arch Public Health. 2003;61(6):313-332.
    1. Flory JD, Yehuda R. Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations. Dialogues Clin Neurosci. 2015;17(2):141-150. doi:10.31887/DCNS.2015.17.2/jflory
    1. Li X, Aida J, Hikichi H, Kondo K, Kawachi I. Association of postdisaster depression and posttraumatic stress disorder with mortality among older disaster survivors of the 2011 Great East Japan Earthquake and tsunami. JAMA Netw Open. 2019;2(12):e1917550-e1917550. doi:10.1001/jamanetworkopen.2019.17550
    1. Edmondson D, Gamboa C, Cohen A, et al. . Association of posttraumatic stress disorder and depression with all-cause and cardiovascular disease mortality and hospitalization among Hurricane Katrina survivors with end-stage renal disease. Am J Public Health. 2013;103(4):e130-e137. doi:10.2105/AJPH.2012.301146
    1. Dao TK, Chu D, Springer J, et al. . Clinical depression, posttraumatic stress disorder, and comorbid depression and posttraumatic stress disorder as risk factors for in-hospital mortality after coronary artery bypass grafting surgery. J Thorac Cardiovasc Surg. 2010;140(3):606-610. doi:10.1016/j.jtcvs.2009.10.046
    1. van den Berk-Clark C, Secrest S, Walls J, et al. . Association between posttraumatic stress disorder and lack of exercise, poor diet, obesity, and co-occuring smoking: A systematic review and meta-analysis. Health Psychol. 2018;37(5):407-416. doi:10.1037/hea0000593
    1. Bao Y, Bertoia ML, Lenart EB, et al. . Origin, methods, and evolution of the three Nurses’ Health Studies. Am J Public Health. 2016;106(9):1573-1581. doi:10.2105/AJPH.2016.303338
    1. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 4th ed American Psychiatric Association; 1994.
    1. Breslau N, Peterson EL, Kessler RC, Schultz LR. Short screening scale for DSM-IV posttraumatic stress disorder. Am J Psychiatry. 1999;156(6):908-911. doi:10.1176/ajp.156.6.908
    1. Andresen EM, Malmgren JA, Carter WB, Patrick DL. Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med. 1994;10(2):77-84. doi:10.1016/S0749-3797(18)30622-6
    1. Cheng S-T, Chan ACM. The Center for Epidemiologic Studies Depression Scale in older Chinese: thresholds for long and short forms. Int J Geriatr Psychiatry. 2005;20(5):465-470. doi:10.1002/gps.1314
    1. Blank K, Gruman C, Robison JT. Case-finding for depression in elderly people: balancing ease of administration with validity in varied treatment settings. J Gerontol A Biol Sci Med Sci. 2004;59(4):378-384. doi:10.1093/gerona/59.4.M378
    1. Akaike H. A new look at the statistical model identification. IEEE Transactions on Automatic Control. 1974;19(6):716-723. doi:10.1109/TAC.1974.1100705
    1. Laursen TM, Musliner KL, Benros ME, Vestergaard M, Munk-Olsen T. Mortality and life expectancy in persons with severe unipolar depression. J Affect Disord. 2016;193:203-207. doi:10.1016/j.jad.2015.12.067
    1. Bonanno GA. Loss, trauma, and human resilience: have we underestimated the human capacity to thrive after extremely aversive events? Am Psychol. 2004;59(1):20-28. doi:10.1037/0003-066X.59.1.20
    1. Gros DF, Price M, Magruder KM, Frueh BC. Symptom overlap in posttraumatic stress disorder and major depression. Psychiatry Res. 2012;196(2-3):267-270. doi:10.1016/j.psychres.2011.10.022
    1. Insel T, Cuthbert B, Garvey M, et al. . Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010;167(7):748-751. doi:10.1176/appi.ajp.2010.09091379
    1. Caspi A, Houts RM, Ambler A, et al. . Longitudinal assessment of mental health disorders and comorbidities across 4 decades among participants in the Dunedin birth cohort study. JAMA Netw Open. 2020;3(4):e203221-e203221. doi:10.1001/jamanetworkopen.2020.3221
    1. Caspi A, Houts RM, Belsky DW, et al. . The p factor: one general psychopathology factor in the structure of psychiatric disorders? Clin Psychol Sci. 2014;2(2):119-137. doi:10.1177/2167702613497473
    1. Caspi A, Moffitt TE. All for one and one for all: mental disorders in one dimension. Am J Psychiatry. 2018;175(9):831-844. doi:10.1176/appi.ajp.2018.17121383
    1. Campbell DG, Felker BL, Liu C-F, et al. . Prevalence of depression-PTSD comorbidity: implications for clinical practice guidelines and primary care–based interventions. J Gen Intern Med. 2007;22(6):711-718. doi:10.1007/s11606-006-0101-4
    1. Ramsawh HJ, Fullerton CS, Mash HBH, et al. . Risk for suicidal behaviors associated with PTSD, depression, and their comorbidity in the U.S. Army. J Affect Disord. 2014;161:116-122. doi:10.1016/j.jad.2014.03.016
    1. Cougle JR, Resnick H, Kilpatrick DG. PTSD, depression, and their comorbidity in relation to suicidality: cross-sectional and prospective analyses of a national probability sample of women. Depress Anxiety. 2009;26(12):1151-1157. doi:10.1002/da.20621
    1. Momartin S, Silove D, Manicavasagar V, Steel Z. Comorbidity of PTSD and depression: associations with trauma exposure, symptom severity and functional impairment in Bosnian refugees resettled in Australia. J Affect Disord. 2004;80(2-3):231-238. doi:10.1016/S0165-0327(03)00131-9
    1. Pittman JOE, Goldsmith AA, Lemmer JA, Kilmer MT, Baker DG. Post-traumatic stress disorder, depression, and health-related quality of life in OEF/OIF veterans. Qual Life Res. 2012;21(1):99-103. doi:10.1007/s11136-011-9918-3
    1. Ikin JF, Creamer MC, Sim MR, McKenzie DP. Comorbidity of PTSD and depression in Korean War veterans: prevalence, predictors, and impairment. J Affect Disord. 2010;125(1-3):279-286. doi:10.1016/j.jad.2009.12.005
    1. Oquendo MA, Echavarria G, Galfalvy HC, et al. . Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder. Neuropsychopharmacology. 2003;28(3):591-598. doi:10.1038/sj.npp.1300050
    1. de Kloet C, Vermetten E, Lentjes E, et al. . Differences in the response to the combined DEX-CRH test between PTSD patients with and without co-morbid depressive disorder. Psychoneuroendocrinology. 2008;33(3):313-320. doi:10.1016/j.psyneuen.2007.11.016
    1. Halbreich U, Olympia J, Carson S, et al. . Hypothalamo-pituitary-adrenal activity in endogenously depressed post-traumatic stress disorder patients. Psychoneuroendocrinology. 1989;14(5):365-370. doi:10.1016/0306-4530(89)90006-1
    1. Young EA, Breslau N. Cortisol and catecholamines in posttraumatic stress disorder: an epidemiologic community study. Arch Gen Psychiatry. 2004;61(4):394-401. doi:10.1001/archpsyc.61.4.394
    1. Buckley JP, Keil AP, McGrath LJ, Edwards JK. Evolving methods for inference in the presence of healthy worker survivor bias. Epidemiology. 2015;26(2):204-212. doi:10.1097/EDE.0000000000000217
    1. Angelakis S, Nixon RD. The comorbidity of PTSD and MDD: implications for clinical practice and future research. Behaviour Change. 2015;32(1):1-25. doi:10.1017/bec.2014.26
    1. Nishith P, Nixon RD, Resick PA. Resolution of trauma-related guilt following treatment of PTSD in female rape victims: a result of cognitive processing therapy targeting comorbid depression? J Affect Disord. 2005;86(2-3):259-265. doi:10.1016/j.jad.2005.02.013

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe