Comparison of Mortality Rates Between Israeli Veterans with And

1 1

Zohar, J., Fostick, L. (2014). Comparison of Mortality Rates between Israeli Veterans With and

Without Post Traumatic Stress Disorder. European Neuropsychopharmachology, 24 , 117–124.

***This is a self-archiving copy and does not fully replicate the published version***

Mortality Rates between Treated Post Traumatic Stress Disorder Israeli

Male Veterans Compared to Non-Diagnosed Veterans

Joseph Zohar 1 and Leah Fostick 2

on behalf of the Israeli Consortium on PTSD*

1Department of Psychiatry, Sheba Medical Center, Tel Hashomer, and Sackler School of

Medicine, Tel Aviv University, Israel

2Ariel University, Ariel, Israel

* The Israeli Consortium on PTSD includes:

J. Zohar (chair), A. Bleich, Z. Kaplan, I. Katz, E. Klein, M. Kotler, A. Ohri, AY. Shalev,

& Z. Weissman.

**Address for correspondence: Prof. J. Zohar, Department of Psychiatry, Sheba Medical

Center, Tel Hashomer 52621, Israel. Telephone: 972-3530-3300. Fax: 972-3535-2788.

Email: [email protected] .

Page 1 of 23 2 2

Abstract

The literature suggests that post-traumatic stress disorder (PTSD) is associated with increased mortality. However, to date, mortality rates amongst veterans diagnosed with post-traumatic stress disorder have not been reported for Israeli veterans, who bear a different profile than veterans from other countries. This study aims to evaluate age- adjusted mortality rates amongst Israeli Defense Forces veterans with and without PTSD diagnosis. The study was carried out in a paired sample design with 2,457 male veterans with treated PTSD and 2,457 matched male veterans without a PTSD diagnosis. Data on

PTSD and non-PTSD veterans was collected from the Rehabilitation Division of the

Israeli Ministry of Defense (MOD) and the Israeli Defense Forces’ (IDF) special unit for treatment of combat stress reaction. Mortality data were collected from the Ministry of the

Interior (MOI) computerized database. Comparison of mortality rates between PTSD and non-PTSD veterans was done using paired observations survival analysis by applying a proportional hazards regression model. Overall no statistically significant difference in mortality rates was found between veterans with treated PTSD and veterans without

PTSD. These findings hold even when excluding veterans who died in battle and including non-PTSD veterans who died before their matched PTSD veteran was diagnosed. However, among pairs with similar military jobs PTSD group had significantly less mortality. The results of this large national cohort suggest that treated

PTSD is not associated with increased mortality. We submit that the lack of this association represents the “net“ pathophysiology of PTSD due to the unique characteristics of the sample.

Keywords: PTSD; Mortality; Veterans

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Introduction

Post-traumatic stress disorder (PTSD) is a chronic and disabling disorder characterized by re-experiencing trauma suffered, avoidance of trauma-related stimuli, restricted affect, hypervigilance, and social isolation (American Psychiatric Association, 2013). PTSD has also been found to be linked to considerable physical comorbidity (Schnurr et al., 1998;

Schnurr & Green, 2004) and increased all-cause mortality (Sareen et al., 2007) (see Table

1 for a review). Increased suicidal behaviors and attempts have been reported in anxiety disorders (Sareen et al., 2005), including PTSD (Pfeiffer et al., 2009).

To date, the majority of studies investigating mortality rates amongst those diagnosed with PTSD have been conducted on Vietnam combat veterans (Table 1) in comparison either with the general U.S. population (Bullman & Kang, 1994; Johnson et al., 2004), those stationed in Vietnam but serving in non-combat roles (Breslin et al., 1998), or U.S. veterans who did not participate in the Vietnam War (Breslin et al., 1998; Bullman &

Kang, 1994; Centers for Disease Control, 1988; Fett et al., 1987; Lawrence et al., 1985;

Sareen et al., 2005, 2007; Schnurr & Green, 2004; Thomas et al., 1991; Watanabe et al.,

1991; Watanabe & Kang, 1995, 1996). These studies evince several confounding effects which are appropriate to be taken into consideration: (1) a priori differences between the veteran population in such a semi-mandatory conscription system as the U.S. Vietnam draft and the general population; (2) a selection bias reflecting the “healthy veteran” effect

– i.e., comparison of mortality rates between a medically-selected group such as veterans and an unselected group such as the general population (Macfarlane et al., 2000; Seltzer

& Jablon, 1974; Watanabe & Kang, 1995); (3) the impact of the high comorbidity of alcohol and drug abuse amongst U.S. veterans with PTSD (Boscarino, 2008a).

The study aim is to evaluate age-adjusted mortality rates and causes of death amongst

Israeli Defense Forces (IDF) veterans diagnosed and treated for PTSD in comparison with

Page 3 of 23 4 4

IDF veterans never diagnosed with PTSD. This cohort potentially differs from those reported in other studies in several ways. Firstly, since military service in Israel is both mandatory and prestigious, Israeli veterans might more accurately represent the general population than other countries where draftees do not come from all walks of life.

Secondly, the selection of cohorts of veterans for both the PTSD and comparison groups should enable a better control of the selection bias deriving from the “healthy veteran” effect. Finally, in contrast to the 11% alcohol abstinence and 35% drinkers reported in

Europe (Neumark et al., 2007), the Israel National Health Survey reports 40% alcohol abstinence and only 10% drinkers reporting three or more drinking episodes weekly.

Since alcohol and drug use are less common in Israel – and thus also in Israeli veterans – this might help to minimize the potentially-confounding effect of these factors on mortality. We therefore propose that this unique sample is well suited for examining the issue of PTSD-related mortality amongst veterans.

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Study procedure

Data collection

The study was part of a survey designed to analyze and characterize Israeli veterans with

PTSD who were referred either to the Rehabilitation Division of the Israeli Ministry of

Defense (MOD) or to the Israeli Defense Forces’ (IDF) special unit for treatment of combat stress reaction. In the survey – conducted between 2000 and 2001 – all the charts from the seven MOD rehabilitation branches and the single IDF center were screened. In this sample, all index participants were veterans who died between 1957 and 2002. The age of death ranged from 22 to 89. The PTSD veterans experienced a traumatic incident either during their mandatory (age 18-21) or reserve service (age 21-45) between 1948 and 2000. Traumatic experiences included: combat action (81.2%), accidents during routine work or training (5.2%), traffic accidents (6.6%), terror attacks (4.0%), and other events (3.0%). The survey covered all the records relating to any psychiatric diagnoses –

5,871 in number, constituting 91% of the existing records of the entire population of those diagnosed with any psychiatric disorder between 1948 and 2000. A diagnosis of

PTSD was found for 2,463 files. As the number of female veterans in the PTSD group was very low (n=6) and their trauma history not combat related, we confined the sample to males. The total number of PTSD files in the current study was 2,457, comprising all the files surveyed for male veterans who met the DSM-IV criteria for PTSD. According to power analysis, this sample size is sufficient to detect differences as small as 3% in mortality rates at 93% power.

Although PTSD diagnosis exists in some of the files, it was reevaluated for all by surveyors on the basis of the veterans’ charts using DSM-IV criteria (American

Psychiatric Association, 1994) – i.e., the person had been exposed to a traumatic event

Page 5 of 23 6 6 and evidenced at least one symptom of re-experiencing, three avoidance/numbing symptoms, and two symptoms of hyper-arousal. The surveyors were 32 psychology students in the final year of their undergraduate studies, who were given specific training in the diagnosis of PTSD. The surveyors were overseen by senior, well-informed supervisors who reevaluated 50% of the files randomly during the first two months for each surveyor, and 25% at subsequent stages. Inter-rater reliability between the surveyors' and the supervisors' diagnoses was found to be within the acceptable range (kappa=0.77).

The data were first coded into data sheets and then entered into a computerized database.

Non-PTSD veterans were matched with PTSD veterans in accordance with their draft identification number. To each PTSD participant, a draftee with a sequential army identification number who did not apply to the MOD or IDF centers for either recognition or psychiatric treatment was assigned. This procedure ensured an identical draft period and age/sex correspondence. To some extent it also ensured the matching of other background variables – such as education and socioeconomic characteristics, since soldiers of the same sex, age, and location being drafted in groups. Sequential draft identification numbers also indicate matched physical characteristics, those with similar abilities being placed in the same units.

Veterans with PTSD did not differ from non-PTSD veterans in age, sex, socioeconomic status, or draft-board assessment (Zohar et al., 2011). The study cohort was comprised of a total of 2,457 male veterans with PTSD and an equal number of matched non-PTSD veterans. The analysis thus included 4,914 participants – more cases than in a previous publication (Zohar et al., 2011) due to the fact that no missing data limitations applied to this study.

The analysis was conducted in 2005 and included a snap-shot collection of mortality data obtained from the Ministry of the Interior’s (MOI) computerized database which, by

Page 6 of 23 7 7 law, covers the entire population. A total of 176 veterans were registered as deceased in

2005. Mortality causes for 120 of the 176 veterans who had died were obtained from the

Ministry of Health registry. Causes of death for the remaining 56 veterans were unavailable. The study was approved by the Institutional Ethics Committee of Chaim

Sheba Medical Center, Israel. Since it was based solely on subjects’ records, no written consent was required. ID numbers were encoded during the analysis and decoded for retrieving data purposes only.

Data analysis

The comparison of mortality rates between treated PTSD and non-PTSD veterans was performed six times: (1) analysis of the total sample; (2) analysis only of veterans who did not die in battle (in order to control for incidents of combat-mortality amongst the non-

PTSD group, all the non-PTSD veterans who died during service and their matched PTSD veterans were excluded); (3) analysis only of pairs in which the non-PTSD veterans died after his matched PTSD veteran developed PTSD symptoms (in order to make PTSD and non-PTSD groups more comparable in terms of length of follow-up, this analysis was restricted to deaths occurring only after the trauma had taken place and PTSD had developed); (4) a final analysis with data cleaned for all the above (i.e., only veterans who did not die in battle and where the non-PTSD veteran did not die before his matched

PTSD veteran developed PTSD symptoms; (5) PTSD and non-PTSD veterans have the same military job (combat/officer vs. non/service back/support); (6) same as 5 with conditions of 2 and 3.

The survival analysis of the paired observations was conducted by applying a proportional hazards regression model. Employing the marginal approach suggested by

Gharibvand and Liu (2009), the model was fitted by applying the SAS PROC PHREG, with a robust sandwich estimate to account for the dependence within pairs. This model

Page 7 of 23 8 8 was found to be adequate in five out of the six cases (analyses 2-6), based on tests regarding the proportionality assumption. The first proportionality assumption was based on the correlation between the Schoenfeld residuals and the ranking of individual failure times. The second ultilized the method proposed by Lin et al (1993), being based on the cumulative sums of martingale residuals. In the single case where the model assumption was found to be inadequate (analysis 1), the stratified log rank was applied.

Results

The demographic characteristics of year of birth, age upon death, draft year, number of years of education, rank, and role during service for the two groups – deceased treated

PTSD and non-PTSD veterans – are described in Table 2. A difference of five years was found between PTSD and non-PTSD veterans in year of death and age upon death, with

PTSD veterans being older. No other differences were found between the two groups.

As seen in Table 3 the results of the survival analysis show that for the entire cohort the difference in survival between PTSD and non-PTSD groups was not statistically signifcant (analysis 1). This remained true when removing death in battle (analysis 2), pairs in which the non-PTSD veteran died prior to PTSD diagnosis (analysis 3), or both

(analysis 4). However, when examining PTSD and non-PTSD veterans with the same military jobs, the PTSD group had significantly less mortalility rates as compared to the non-PTSD (analysis 5), even after removing death in battle and pairs where the non-

PTSD veteran died prior to PTSD diagnosis (analysis 6).

Causes of death according to ICD-10 classification were coded and are described in

Table 4. Due to the small number of observations, no analysis was carried out on this data.

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Discussion

No statistically-significant difference obtained between the age-adjusted mortality rate of veterans with treated PTSD and that of non-PTSD veteran which were matched on age, sex, and combat role during exposure to trauma . Moreover, when controlled for military job, less mortality rates were found for treated PTSD than to non-PTSD veterans. This finding is contrary to the majority of publications on the subject (see Table 1).

Conceivably, the unique population of this study might account for a portion of these differences. The current sample represents the general population due to compulsory conscription in Israel, while since most of the previous publications relate to voluntary drafting cases (as obtains in the U.S. and the U.K.), it is subject to population bias.

Recent findings show no excess of mortality amongst U.K. veterans (not limited to those diagnosed with PTSD) (Macfarlane et al., 2000, 2005), and lower rates of suicide among depressed veterans with comorbid PTSD (Pfeiffer et al., 2009; Zivin et al., 2007).

The current study expanded these findings by focusing exclusively on mortality rates veterans diagnosed with PTSD. To the best of our knowledge, it constitutes the first study to examine the association between PTSD and mortality amongst Israeli veterans. In light of findings of mortality excess amongst veterans with PTSD in other studies (Boscarino,

2008a, 2008b; Bullman et al., 1990; Drescher et al., 2003; Johnson et al., 2004; Thomas et al., 1991), we submit that the variant findings of this study might be related to the uniqueness of the Israeli veteran sample. In contrast to the U.S., service in Israel is mandatory, holds a very broad consensus, and affords far fewer loopholes for avoiding the draft. The sample thus reflects virtually all social layers within the population.

A further potential difference between this and other studies which should be addressed relates to drugs and alcohol abuse. During the years covered by this study

Page 9 of 23 10 10 neither alcohol nor drug abuse were common in Israeli society (Neumark et al., 2007).

This study correspondingly found a relatively low rate of drug and alcohol usage amongst veterans – in direct contrast to the widespread prevalence of drug and alcohol usage amongst U.S. veterans, mostly Vietnam veterans (Boscarino, 2008a). The benefit of studying veterans with low drug and alcohol comorbidity lies in the fact that the results might reflect the “net” effect of PTSD on mortality without any "contamination" from these confounders (Johnson et al., 2004), although it also might limits the generalizability of the findings. We thus suggest that the above-mentioned advantages of the present sample may account – at least partially – for the difference in the results obtained in this rather “cleaner” sample as compared to other studies, wherein the PTSD sample may have evinced a higher level of socio-economic and comorbidity confounds. Yet additional explanation for these results could lay in the difference between Israel and other countries in higher social benefit and standard healthcare provided for those who are recognized as injured in battle. This also might lead to a situation in which not all the veterans in the

PTSD group are actually suffer from PTSD, as some of them might over-report their

PTSD symptoms.

An interesting finding repeatedly reported in previous studies of people with PTSD – as well as in some cases comparing deployed vs. non-deployed veterans (Macfarlane et al., 2000, 2005)– is the presence of excess mortality due to external causes (Boscarino,

2006a, 2006b; Breslin et al., 1998; Bullman et al., 1990; Bullman & Kang, 1994; Centers for Disease Control, 1988; Drescher et al., 2003; Fett et al., 1987; Johnson et al., 2004;

Kang & Bullman, 1996; Watanabe et al., 1991; Watanabe & Kang, 1995, 1996), especially suicide (Breslin et al., 1998; Bullman & Kang, 1994; Centers for Disease

Control, 1988; Drescher et al., 2003; Ferrada-Noli et al., 1998; Watanabe & Kang, 1996).

The results of the current study demonstrate a similar tendency towards excess mortality

Page 10 of 23 11 11 due to external causes (including injury and poisoning) amongst PTSD veterans in comparison with non-PTSD veterans (18 vs. 8, respectively; Table 4). Mortality due to external causes can point to a set of behavioural characteristics possibly associated with suicide and suicidal behaviour. The numerical excess of deaths related to injury and poisoning in the PTSD group corresponds to this hypothesis.

One of the limitations of this study is the apparent difficulty in distinguishing suicide from other causes of death in the database due to cultural-religious confounds. According to religious law (e.g., Jewish and Muslim), a person who commits suicide must be buried on the outskirts of the cemetery (“near the fence”). The burial consequences of suicide lead physicians responsible for recording cause of death to be extremely careful and to avoid registering death as suicide, self-inflicted injury (code E950-E959, ICD-9), or intentional self-harm (code X60-X84, ICD-10) unless left with no other recourse. Indeed, only in the case of two veterans (one PTSD and one non-PTSD) was the mortality cause classified as ”intentional self-harm” (code X60-X84, ICD-10).

Additional shortcomings are that the PTSD group was diagnosed based on chart review, and that the non-PTSD group was defined on the basis of lack of referral rather than via a systematically-structured diagnostic questionnaire, thereby hampering our ability to assess whether veterans in the non-PTSD group actually suffer from PTSD.

Since referral to the MOD and IDF following combat-related trauma is not rare, however, we suspect this group to be rather small. The complementing limitation is that – in similar fashion to other studies in the field – we only tested PTSD veterans who applied for treatment, the results consequently being limited to this group. Given the awareness of

PTSD in veterans in Israel and the substantial financial benefits and treatment provided by the MOD, we opine that many (if not a majority) of the veterans with PTSD applied for treatment.

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Other limitations could relate to other variables not measured in the study, such as social support and family bonding, which, differing between Israel and the U.S. might explain the variation in the results. Similarly, both the current study and previous studies surveying military veterans exclusively observed males, whereas PTSD is more prevalent amongst women. The implications of these studies are therefore limited to the male population.

The finding of no mortality excess among treated PTSD veterans in this sample, and even lower mortality rates when controlling for army job during the incident, appears not only to differ from the literature on higher mortality rates amongst civilians and veterans

(Boscarino, 2006a, 2006b, 2008a, 2008b; Breslin et al., 1998; Bullman et al., 1990;

Bullman & Kang, 1994; Centers for Disease Control, 1988; Fett et al., 1987; Drescher et al., 2003; Ferrada-Noli et al., 1998; Johnson et al., 2004; Mollica, et al., 2001; Thomas et al., 1991; Watanabe et al., 1991; Watanabe & Kang, 1995, 1996), but also to be somewhat counterintuitive. Individuals with PTSD are not only subject to considerable stress but also evince a high comorbidity of depression, thus being expected to be more prone to stress-related morbidity and increased mortality. A similar pattern of results was found amongst Holocaust survivors, whereas no mortality excess was found in comparison with age-matched individuals unexposed to the Holocaust (Collins et al., 2004; Stessman et al.,

2008). Previously it was suggested that lower rates of suicide among depressed veterans with comorbid PTSD as compared to depressed veterans without PTSD can be explained by having more psychotherapeutic attention for those who have PTSD (Pfeiffer et al.,

2009; Zivin et al., 2007), which might also be the case here. However, it is not clear whether PTSD veterans are being followed more closely medically (since they are already being monitored by their physicians for their PTSD) or, conversely, whether they are more sensitive to threats (both internal and external) and therefore seek help more

Page 12 of 23 13 13 frequently. These and other factors are yet to be explored. For example, stress per se has traditionally been associated with a higher occurrence of “diseases of the circulatory system”. In this sample, however, a numerical excess of deaths in this system was observed in the non-PTSD rather than the PTSD group.

If replicated, the principal finding of the study – namely, that treated PTSD veterans evinced no age-adjusted mortality excess – might shed new light on the complex interaction between stress and mortality. PTSD – a disorder closely linked to death and/or fear of dying – was not associated with actual mortality rates. Although power analysis found that the sample size of 2,457 in each group is sufficient to detect even a small differences (as small as 3%) in mortality rates, this finding could still be reversed.

Therefore, this finding requires further exploration and re-examination in another 10-15 years, when more incidents of death will have occurred in both PTSD and non-PTSD groups.

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References

American Psychiatric Association, 2013. Diagnostic and statistical manual of mental disorders. 5th edition ed. Arlington, VAWashington, DC: American Psychiatric

Association.

Boscarino, J. A., 2006. External-cause mortality after psychologic trauma: the effects of stress exposure and predisposition. Compr. Psychiat.47(b), 503-14.

Boscarino, J. A., 2006. Posttraumatic stress disorder and mortality among U.S.

Army veterans 30 years after military service. Ann. Epidemiol. 16(a), 248-56.

Boscarino, J. A., 2008. A prospective study of PTSD and early-age heart disease mortality among Vietnam veterans: Implications for surveillance and prevention.

Psychosom. Med. 70b, 668-76.

Boscarino, J. A., 2008. Psychobiologic predictors of disease mortality after psychological trauma. Implications for research and clinical surveillance. J. Nerv. Ment.

Dis. 196a, 100-107.

Breslin, P., Kang, H., Lee, Y., Burt, V., & Shepard, B., 1998. Proportionate mortality study of US Army and US Marine Corps veterans of the Vietnam War. Occup.

Environ. Med. 30, 412-19.

Bullman, T., & Kang, H., 1994. Posttraumatic stress disorder and the risk of traumatic deaths among Vietnam veterans. J. Nerv. Ment. Dis. 182, 604-10.

Bullman, T., Kang, H., & Watanabe, K.,1990. Proportionate mortality among US

Army Vietnam veterans who served in military region I. Am. J. Epidemiol. 132, 670-4.

Centers for Disease Control., 1988. Serum 2, 3,7,8-tetrachlorodibenzo-p-dioxin levels in US Army Vietnam-era veterans. JAMA.

Page 14 of 23 15 15

Collins, C., Burazeri, G., Goﬁn, J., & Kark, J., 2004. Health status and mortality in holocaust survivors living in Jerusalem 40–50 Years Later. J. Trauma. Stress. 17, 403-

411.

Drescher, K., Rosen, C., Burling, T., & Foy, D., 2003. Causes of death among male veterans who received residential treatment for PTSD. J. Trauma. Stress. 16, 535-43.

Ferrada-Noli, M., Asberg, M., Ormstad, K., Lundin, T., & Sundbom, E., 1998.

Suicidal behavior after severe trauma. Part 1: PTSD diagnoses, psychiatric comorbidity, and assessments of suicidal behavior. J. Trauma. Stress. 11, 103-12.

Fett, M., Nairn, J., Cobbin, D., & Adena, M., 1987. Mortality among Australian conscripts of the Vietnam conflict era. II. Causes of death. Am. J. Epidemiol.125, 878-84.

Gharibvand, L., & Liu, L., 2009. Analysis of survival data with clustered events.

Paper 237-2009. Washington, DC: SAS Global Forum Proceedings.

Johnson, D., Fontana, A., Lubin, H., Corn, B., & Rosenheck, R., 2004. Long-term course of treatment-seeking Vietnam veterans with posttraumatic stress disorder: mortality, clinical condition, and life satisfactio. J. Nerv. Ment. Dis. 192, 35-41.

Kang, H., & Bullman, T., 1996. Mortality among U.S. veterans of the Persian Gulf

War. N. Engl. J. Med.335, 1498-504.

Lawrence, C., Reilly, A., Quickenton, P., Greenwald, P., Page, W., & Kuntz, A.

(1985). Mortality patterns of New York State Vietnam Veterans. Am. J .Public Health.

75, 277-79.

Lin, D., Wei, L., & Ying, Z., 1993. Checking the Cox model with cumulative sums of martingale based residuals. Biometrika, 80, 557-572.

Macfarlane, G. J., Hotopf, M., Maconochie, N., Blatchley, N., Richards, A., & Lunt,

M., 2005. Long-term mortality amongst Gulf War Veterans: Is there a relationship with

Page 15 of 23 16 16 experiences during deployment and subsequent morbidity? Int. J. Epidemiol. 34, 1403-

1408.

Macfarlane, G. J., Thomas, E., & Cherry, N., 2000. Mortality among UK Gulf War veterans. Lancet, 356, 17-21.

Mollica, R., Sarajlic, N., Chernoff, M., Lavelle, J., Vukovic, I., & Massagli, M.,

2001. Longitudinal study of psychiatric symptoms, disability, mortality, and emigration among Bosnian refugees. JAMA, 286, 546-54.

Neumark, Y., Lopez-Quintero, C., Grinshpoon, A., & Levinson, D., 2007. Alcohol drinking patterns and prevalence of alcohol-abuse and dependence in the Israel National

Health Survey. Isr. J. Psychiatry. Relat. Sci. 44, 126-35.

Pfeiffer, P., Ganoczy, D., Ilgen, M., Zivin, K., & Valenstein, M., 2009. Comorbid anxiety as a suicide risk factor among depressed veterans. J. Depress. Anxiety. 26, 752-

757.

Sareen, J., Cox, B., Afifi, T., de Graaf, R., Asmundson, G., ten Have, M., & Stein,

M., 2005. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch. Gen. Psychiatry. 62, 1249-5.

Sareen, J., Cox, B., Stein, M., Afifi, T., Fleet, C., & Asmundson, G., 2007. Physical and mental comorbidity, disability, and suicidal behavior associated with posttraumatic stress disorder in a large community sample. Psychosom. Med. 69, 242-8.

Schnurr, P., & Green, B., 2004. Understanding relationships among trauma, posttraumatic stress disorder, and health outcomes. Adv. Mind. Body. Med. 20, 18-29.

Schnurr, P., Spiro, A. 3., Aldwin, C., & Stukel, T., 1998. Physical symptom trajectories following trauma exposure: longitudinal findings from the normative aging study. J. Nerv. Ment. Dis. 186, 522-8.

Page 16 of 23 17 17

Seltzer, C., & Jablon, S., 1974. Effects of selection on mortality. Am. J. Epidemiol,

100, 367-72.

Stessman, J., Cohen, A., Hammerman-Rozenberg, R., Bursztyn, M., Azoulay, D.,

Maaravi, Y., & Jacobs, J., 2008. Holocaust survivors in old age: The Jerusalem longitudinal study. J. Am. Geriatr. Soc. 56, 470-477.

Thomas, T., Kang, H., & Dalager, N., 1991. Mortality among Vietnam veterans,

1973-1987. Am. J. Epidemiol. 134, 973-80.

Watanabe, K., & Kang, H., 1995. Military service in Vietnam and the risk of death from trauma and selected cancers. Ann .Epidemiol. 5, 407-12.

Watanabe, K., & Kang, H., 1996. Mortality patterns among Vietnam veterans: a 24- year retrospective analysis. Occup. Environ. Med. 38, 272-78.

Watanabe, K., Kang, H., & Thomas, T., 1991. Mortality among Vietnam veterans: with methodological considerations. Occup. Environ. Med., 33, 780-85.

Zivin, K., Kim, M., McCarthy, J., Austin, K., Hoggatt, K., Walters, H., &

Valenstein, M., 2007. Suicide mortality among individuals receiving treatment for depression in the Veterans Affairs health system: Associations with patient and treatment setting characteristics. Am. J .Public Health. 97, 2193-2198.

Zohar, J., Yahalom, H., Koslovsky, N., Cwikel-Hamzany, S., Matar, M., Kaplan, Z.,

& Cohen, H., 2011. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: Interplay between clinical and animal studies.

Eur.Neuropsychopharmacol. 21(11), 796-809.

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Table 1. Review of papers studying the relationship between PTSD and mortality

Paper Study group N Comparison N Excess mortality Cause of death

group rates amongst

study group?

Bullman & USA Vietnam 6,668 Non-Vietnam 27,917 Yes Accidental poisoning

Kang, veterans veterans Motor accidents

1990 [6] diagnosed

with PTSD

Bullman & USA Vietnam 4,247 Non-PTSD 12,010 Yes Suicide

Kang, veterans Vietnam Accidental poisoning

1994 [7] diagnosed veterans All causes

with PTSD US males

Mollica et Bosnian 139 Bosnian 389 No

al., 2001 refugees refugees not

[8] diagnosed diagnosed

with PTSD with PTSD

Drescher et USA dead 1,866 General General Yes Accidents

al., 2003 male population population Motor vehicle accidents Overdose [9] veterans norms norms Injury diagnosed Intentional deaths with PTSD Suicide

Effects of chronic substance use Alcoholic liver cirrhosis Alcohol dependence

HIV/hepatitis

Liver disease (unrelated to

alcohol)

Page 19 of 23 2 0 20

Johnson et USA Vietnam 154 USA males USA males Yes

al., 2004 veterans aged 45-54 aged 45-54

[10] diagnosed

with PTSD

Boscarino USA Vietnam 1,050 Non-PTSD 14,238 Yes

2006 [11, theater and era Vietnam theater

12], veterans and era veterans

diagnosed with

PTSD

Ferrada- Refugees 117 Refugees not 32 Yes Suicide

Noli et al., diagnosed diagnosed with

1998 [13] with PTSD PTSD

Boscarino, USA Vietnam 323 Vietnam 4,139 Yes All causes

2008a [14] veterans veterans (theater Cardiovascular-related

(theater and and era) not conditions

era) diagnosed diagnosed with External causes with PTSD PTSD Cancer

Infectious diseases

Digestive conditions

Other disease-related

conditions

Boscarino, USA Vietnam 311 Vietnam 4,017 Yes

2008b [15] veterans veterans (theater

(theater and and era) not

era) diagnosed diagnosed with

with PTSD PTSD

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Table 2. Demographic characteristics of all cohort and of only deceased PTSD and non- PTSD veterans All Deceased PTSD Non- Significance and PTSD Non- Significance and PTSD Effect Size PTSD Effect Size (95% (95% CI) * CI) *

Year of birth Mean= 1955.1 1955.7 t=1.27, p=.21 1945 1940 t(173.1) =2.3, p<.02, SD= 9.80 10.5 ES=-.06 (-.11; 10.14 14.73 ES=.39 (.08; .68) n= 2457 2457 .00) 75 101

Age upon death Mean= (See Deceased 49.88 45.5 t(170.1) =2.11, SD= column) 10.63 16.81 p=.04, ES=.30 n= 75 101 (.00; .60)

Draft year Mean= 1974.6 1974.5 t=.60, p=.54 1969 1967 t(73) =.91, p=.37 SD= 9.03 9.18 ES=.01 (-.05; 8.29 8.10 ES=.25 (-.32; n= 2269 2279 .07) 15 60 .81) No. of years of Mean= 10.1 10.1 t=.56, p=.58 9.15 8.81 t=.54, p=.59 education SD= 2.1 2.3 ES=.00 (-.06; 1.68 3.25 ES=.11 (-.49; n= 2184 2110 .06) 13 58 .71) 2 2 Marital status χ (3) 14.1, χ (3) =.83, p=.84 p=.003 Single 11.3% 14.5% 22.2% 26.6% (n=270) (n=349) (n=4) (n=25) Married 81.3% 77.2% 61.1% 58.5% (n=1950) (n=1853) (n=11) (n=55) Divorced 6.8% 7.7% 11.1% 12.8% (n=163) (n=185) (n=2) (n=12) Widower 0.6% 0.5% 5.6% 2.1% (n=15) (n=13) (n=1) (n=2) 2 2 Rank during χ (1) = 4.1, p=.04 χ (3) =1.41, p=.77 incident Private 71.7% 68.8% OR=1.15 (1.00; 75% 69% OR=1.33 (.38; (n=1471) (n=1413) 1.31) (n=12) (n=43) 4.64) Sergeant** 28.3% 31.2% 25% 31% (n=582) (n=642) (n=4) (n=19) 2 2 Role during χ (1) = 30.0, χ =(3) 7.12, p=.27 incident p<.001 Combat 46.6% 37.7% OR=1.44 (1.26; 63% 45% OR=2.04 (.66; (n=898) (n=691) 1.64) (n=10) (n=27) 6.32) Service 53.4% 62.3% 37% 55% (n=1031) (n=1141) (n=6) (n=33) *Effect Size is mean difference/ pooled standard deviation or odd ratio for dichotomous variables. **Includes 5 officers in the non-PTSD group

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Table 3. Number of deceased PTSD and non-PTSD veterans

Total No. of No. of deceased Hazards 95% confidence No. deceased amongst ratio interval amongst non-PTSD (0=non- PTSD PTSD; 1=PTSD)* Analysis 1 4,914 75/2382 101/2356 .73 0.44-1.02, p=.26 Analysis 2 4,904 75/2382 91/2356 .91 0.66-1.24, p=.19 Analysis 3 4,892 75/2382 79/2356 .94 0.77-1.46, p=.88 Analysis 4 4,889 75/2382 76/2356 .94 0.77-1.46, p=.88 Analysis 5 2,360 10/1170 33/1147 .30 0.14-0.63, p=.00 Analysis 6 2,348 10/1170 21/1147 .47 0.22-1.01, p=.05 Analyses: (1) All participants (2) persons who did not die in battle; (3) Only of pairs in which the non-PTSD veterans died after his matched PTSD veteran developed PTSD symptoms; (4) Conditions 1 & 2 (only veterans who did not die in battle and where the non-PTSD veteran did not die before his matched PTSD veteran developed PTSD symptoms); (5) PTSD and control veterans have the same military job (combat/officer vs. non/service back/support); (6) same as 5 with conditions of 2 and 3. *Survival anlaysis of matched pairs using proportional hazards regression model

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Table 4. Causes of death by ICD-10 amongst PTSD and non-PTSD veterans

Cause of death PTSD Control Certain infectious and parasitic diseases 2 (3%) 2 (2%) Neoplasms 18 (24%) 12 (12%) Diseases of blood and blood-forming organs 0 1 (1%) Endocrine, nutritional, and metabolic diseases 1 (1%) 1 (1%) Mental disorders 0 3 (3%) Diseases of the nervous system 1 (1%) 0 Diseases of the circulatory system 13 (17%) 23 (23%) Diseases of the respiratory system 0 2 (2%) Diseases of the digestive system 2 (3%) 1 (1%) Diseases of the genitourinary system 2 (3%) 0 Symptoms, signs, and ill-defined conditions 5 (7%) 5 (5%) Injury and poisoning 13 (17%) 6 (6%) External causes of morbidity and mortality 5 (7%) 2 (2%) Missing data 13 (17%) 43 (42%)

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