PTSD and depression as predictors of physical health-related quality of life in tobacco-dependent veterans

Journal of Psychosomatic Research 73 (2012) 185–190

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Journal of Psychosomatic Research

PTSD and depression as predictors of physical health-related quality of life in tobacco-dependent veterans Laura H. Aversa a, b,⁎, Jill A. Stoddard b, Neal M. Doran c, Selwyn Au d, Bruce Chow d, Miles McFall e, f, Andrew Saxon e, f, Dewleen G. Baker a, c, g a

Veterans Affairs San Diego Healthcare System, San Diego, CA, United States California School of Professional Psychology, Alliant International University, San Diego, CA, United States Department of Psychiatry, University of California, San Diego, CA, United States d Cooperative Studies Program, Veterans Affairs Palo Alto Health Care System, Mountain View, CA, United States e Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States f Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States g Veterans Affairs Center of Excellence for Stress and Mental Health, San Diego, CA, United States b c

a r t i c l e

i n f o

Article history: Received 26 April 2012 Received in revised form 25 June 2012 Accepted 25 June 2012 Keywords: Health-related quality of life PTSD Depression Smoking Tobacco SF-36

a b s t r a c t Objective: Smoking, depression and PTSD are related to poor physical health outcomes and health-related quality of life (HRQoL). Previous studies examining the effects of quitting smoking on HRQoL have been mixed. This study aimed to examine the effects of PTSD, depressive symptoms and smoking cessation on HRQoL in a sample receiving treatment for PTSD. Method: This study utilized archival interview and self-report data from a clinical trial (VA Cooperative Study 519) that recruited tobacco dependent veterans with chronic PTSD (N = 943). Results: Analyses were conducted using hierarchical linear modeling and indicated that PTSD and depressive symptoms differentially affected the various physical health status domains. Additionally, quitting smoking was associated with better self-perceived health status and social functioning. Conclusion: Our findings further explain the interrelationships of PTSD, depression, and smoking in the prediction of physical HRQoL and advocate the importance of integrated care. © 2012 Elsevier Inc. All rights reserved.

Introduction Tobacco use, depression, and posttraumatic stress disorder (PTSD) are related to physical and mental health outcomes, including multi-morbidity and death [1–4]. Traditionally, morbidity and mortality risk is adjusted based on chronic medical conditions, laboratory tests, and health risk behaviors. However, researchers who take a biopsychosocial perspective have argued that self-perception of health and its relationship to impairment in day-to-day functioning are important health indicators that predict morbidity and mortality [5,6]. Health-related quality of life (HRQoL) is a construct that reflects individuals' perceptions of their health status. The World Health Organization defines HRQoL as physical, mental, and social well-being as opposed to the mere absence of disease. Better health status, quantified as less morbidity and impairment, is associated with higher HRQoL [7]. The concept of HRQoL is important because it has been shown to predict both morbidity and mortality in populations with chronic ⁎ Corresponding author at: VA San Diego Healthcare System, 3350 La Jolla Village Dr. 151, San Diego, CA 92161, United States. Tel.: +1 858 356 4349; fax: +1 858 642 3851. E-mail address: [email protected] (L.H. Aversa). 0022-3999/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpsychores.2012.06.010

medical conditions including heart disease patients, dialysis patients, asthmatics, and individuals diagnosed with chronic obstructive pulmonary disease [8–15]. Tobacco use, PTSD, and depression have all demonstrated negative, independent associations with HRQoL [16–20]. This study aimed to examine the combined effect of PTSD, depression, and cigarette smoking on physical HRQoL as the three predictor variables have a history of interrelation. Individuals and veterans with PTSD and depression smoke at higher rates than the general population (45% and 37%, respectively, versus 20%; [21,22]). In the active-duty military tobacco use rates are reported anywhere from 23 to 33%, which are higher than the rate of the general population (20%), but not as high as those with co-morbid psychopathology [23,24]. PTSD and depression comorbidity have been estimated to range between 66 and 77% in civilian and veteran samples [25,26]. It has been postulated that overlap in some symptoms of PTSD and depression may inflate the co-morbidity rate [27]; however, depression has been shown to have an independent effect on trauma, and pre-morbid depression is a risk factor for developing PTSD [28,29]. Co-morbid psychiatric conditions are also associated with increased PTSD symptom severity and poor treatment outcomes [30,31]. However, others have found that the use of exposure therapy to treat PTSD can improve general anxiety and

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depressive symptoms and quality of life outcomes [32–35], though only half of the participants in these studies returned to normative levels of functioning [32,33,35]. Examination of the combined effects of PTSD, cigarette smoking, and depression on physical HRQoL has been limited and produced mixed findings. Most studies have recognized independent effects for both depression and PTSD on physical HRQoL [36–38]. While some studies have found that a diagnosis of PTSD explains a larger proportion of the variance in health status than major depression [39,40], others argue that the interaction of the two has the largest effect on physical HRQoL [41,42]. Lastly, many have found that the main effect of depression is the strongest predictor of physical HRQoL holding PTSD constant [43–45]. Studies have generally failed to demonstrate an effect of tobacco use on physical HRQoL when PTSD and depression are included in the models [17,19,46]. The purpose of the present study was to look at the effect of quitting smoking versus continuing to smoke in a sample of veterans diagnosed with PTSD, 75% of whom met criteria for lifetime diagnosis of Major Depressive Disorder [47]. Studies on the effects of quitting smoking on HRQoL are limited, and have been examined only in non-psychiatric samples. Only one of the studies was a longitudinal design, and overall results have shown that the net effects of quitting smoking on HRQoL are inconsistent, small, and may be more substantial across mental than physical health domains [48–50]. The aim of this study was to test the hypothesis that successfully quitting smoking would be associated with improvements in HRQoL only if PTSD or depressive symptoms also improved over time. We hypothesized that quitting smoking in interaction with an improvement in psychiatric symptoms would improve HRQoL in a chronic psychiatric, tobacco-dependent sample based on literature supporting a relationship between improvement in PTSD and depressive symptoms and improvement in HRQoL over time [51–53].

Method Study participants This study utilized archival data collected under Veterans Affairs (VA) Cooperative Study #519, a randomized, controlled, 10-site clinical trial that examined a cognitive–behavioral smoking cessation intervention that was integrated into participants' individual PTSD psychotherapy. Individual PTSD treatment providers followed a manualized, CBT-based smoking cessation protocol as part of weekly sessions with the participant for PTSD treatment, devoting a portion of the session to smoking cessation. Providers were rated for compliance with the treatment protocol by recording a full-course of treatment with a participant that was independently rated by the Mayo Clinic. Participants completed five core smoking cessation sessions with three follow-up sessions, then monthly follow-up as needed [47]. Participants were included in the original trial if they met DSM-IV diagnostic criteria for current PTSD, smoked ≥10 cigarettes/day for >50% of the days in the past month without use of other tobacco products, and were engaged in PTSD treatment in a VA outpatient program. Participants were excluded if currently diagnosed with a psychotic disorder, unstable bipolar disorder, alcohol or substance dependence not in remission, posed an imminent threat of suicide or violence, or demonstrated gross impairment due to an organic mental disorder. Participants were randomized at the pre-treatment visit into either the experimental, integrated smoking cessation intervention or treatment as usual (TAU), meaning participants received smoking cessation treatment at a VA primary care clinic in a group format and separately received individual PTSD outpatient treatment. PTSD treatment was not standardized as part of the original clinical trial. Therefore, type and amount of PTSD treatment received (i.e., evidenced-based) were not controlled for as part of the study. The study took place before

the widespread implementation of evidence-based treatments for PTSD within VA. Measures Health status in the past month was assessed using the Veterans Short-Form 36 (VR-36) Health Survey at two time points, pre- and post-treatment (18-month follow-up). The VR-36 is a version of the Medical Outcomes Short-Form 36 (SF-36) that has been validated in veteran samples. Cronbach's alpha for the VR-36 ranged from .86 to .96 across the eight subscales and was comparable to the psychometrics for the SF-36 [54]. The first ninety-four enrollees completed the original SF-36 and the remaining 849 enrollees completed the VR-36. PTSD symptoms in the past month anchored to a military-related trauma were assessed using the interviewer-assisted ClinicianAdministered PTSD Scale (CAPS) at two time points, pre- and posttreatment. The CAPS has been found to have good internal consistency in veteran samples, with Cronbach's alpha values> .90 for all 17-items [55]. PTSD symptoms were also assessed at seven time points, in three month intervals from pre- to post-treatment, using the self-report, Posttraumatic Stress Disorder Checklist, Military Version (PCL-M), which anchors the respondent to symptoms related to a stressful military experience in the past month. Internal consistency is good with Cronbach's alpha > .94 [56,57]. Depressive symptoms were also measured at every three month interval between pre- and post-treatment with the self-report, Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is the depression module of the PRIME-MD, which assesses the 9 DSM-IV criteria over the past 2 weeks; Cronbach's alpha has been reported to be .89 [58]. Additionally, smoking status was assessed every 3 months from pre- to post-treatment. Participants reported average number of cigarettes smoked per day in the past 3 months. If participants reported 7-day abstinence, smoking cessation was bio-verified by expired carbon monoxide of b8 ppm and a urine cotinine level of b100 ng/ml [47]. Prolonged abstinence (PA) was defined as bio-verified abstinence for 1 year from the 6-month through the 18-month follow-up visits without relapse [47]. Statistical analyses Preliminary analyses examined interrelationships among variables included in the analyses to rule out possible confounds. Variables found to be significant confounds were included as covariates in the multivariate analyses. We used hierarchical linear modeling (HLM), implemented via the xtmixed module in Stata SE 10.1 (StataCorp, College Station, TX), to estimate the relation of changes in PTSD, depressive symptoms and smoking status over time to changes in the Physical Component Summary (PCS) of the VR-36 and its six subscales, Physical Functioning, Role—Physical, Bodily Pain, General Health, Vitality, and Social Functioning. All continuous variables were centered. For models including higher order interaction terms, non-significant higher order terms were removed in a backwards manner, and the model was re-fit. A maximum-likelihood approach was utilized, meaning that missing data points were imputed using multiple imputation methods. To test our hypothesis that depression, PTSD and quitting would interact to predict HRQoL changes over time, a four-way prolonged abstinence (PA) × Time × PHQ-9 Total Score × PCL-M Total Score or CAPS Total Score interaction was tested for physical HRQoL and then for each physical HRQoL subscale outcome, resulting in seven total models. HLM uses a time-series approach to estimate the effect of quitting smoking at post-treatment, a dichotomous variable indicating a prolonged period of abstinence between the 6 and 18-month followup visits, in interaction with PTSD and depressive symptom ratings measured at multiple time points (seven in total for the PCL and PHQ-9, two for the CAPS) on the change in HRQoL ratings from pre-

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to post-treatment (two time points). A significant interaction would indicate that quitting smoking in combination with change in PTSD and depressive symptoms would result in change in physical HRQoL over time. A family-wise Bonferroni correction was incorporated to account for the number of tests performed, adjusting statistical significance to p = .007. Results Sample characteristics Cooperative Study 519 (CSP 519) randomized 945 participants. Two rescinded HIPAA authorization leaving a study sample of n = 943. The characteristics of the sample reported at the baseline visit are detailed in Table 1. Most enrollees were men (94%), which is consistent with gender distribution in the veteran population [59]. The average age was 54 years old (SD = 8.7). Nearly half of the sample identified as an ethnic or racial minority (42%). Three‐quarters of the sample (77%) endorsed the Vietnam War as their earliest period of service. Earliest period of service and treatment site were found to be confounds and were controlled for in each analysis, meaning that there were statistically significant differences in HRQoL scores across period of service with younger, Iraq/Afghanistan veterans reporting higher physical HRQoL scores than older Vietnam era veterans at baseline. Younger, Iraq/Afghanistan veterans also dropped out of the study at higher rates compared to older veterans, and there was differential dropout rate by VA hospital site. Average daily cigarette intake was slightly above one pack (M = 21.7, SD = 10.5) at baseline. Sixty-three participants achieved bio-verified prolonged abstinence between the 6-month and 18-month visits, 42 (8.9%) in the integrated care group and 21 (4.5%) in the usual care group. Both treatment groups had reductions in cigarettes per day post-treatment (M = 13.1, SD = 9.9). The between group difference in cigarettes per day post-treatment was not statistically significant; however, as reported previously there were statistically significant differences in achievement of one-year prolonged abstinence, with integrated care meeting prolonged abstinence criteria at twice the rate of usual care [47]. In terms of PTSD symptoms, baseline CAPS scores (M = 75.2, SD = 18.5) indicated a clinically severe sample [60]. CAPS cluster scores for re-experiencing, effortful avoidance, emotional numbing, and hyperarousal were calculated based on a four-factor model [61]. The baseline PCL-M scores were indicative of diagnostic levels of PTSD (M = 59.2, SD = 12.0; [62]). Baseline PHQ-9 scores indicated an average level of moderate depression (M = 16.0, SD = 6.9; [63]). PTSD symptoms improved over the course of the study in both treatment groups, and the difference from baseline to post-treatment was statistically significant; depressive symptoms did not change [47]. Baseline health status characteristics of the sample are detailed in Table 2. All average subscale scores were below the 25th percentile compared to age-matched population norms for the SF-36, indicating poor health related quality of life [64]. Omnibus PCS and MCS scores did not change over time (M = 37.4, SD = 10.4 and M = 33.9, SD = 10.3, respectively). The role of PTSD, depression, and smoking cessation in the prediction of physical HRQoL The four-way PA × Time × PHQ-9 Total Score × PCL-M Total Score interaction was not a statistically significant predictor of physical health-related quality of life; the four-way interaction term was removed and the model was re-fit. The three-way Table 1 Baseline characteristics of the study sample (N = 943) Demographics

Mean

SD

Age Race/ethnicity White Black Hispanic Other Period of service Vietnam Gulf War OEF/OIF Korea/WWII None of the above Mental health symptoms Total CAPS score (item #s) Intrusive symptoms (B1–B5) Avoidance symptoms (C1–C2) Numbing symptoms (C3–C7) Hyperarousal symptoms (D1–D5) PCL total score PHQ-9 total score

54.1 N 547 345 39 12 N 782 79 56 11 69 Mean 75.24 20.16 9.95 20.40 24.73 55.22 15.96

8.7 % 58 37 4 1 % 77 8 6 1 8 SD 18.5 7.4 3.7 7.5 6.1 12.0 6.9

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Table 2 Baseline health status characteristics of the study sample (N = 943) Mean

SD

VR-36 summary scores Physical Composite Score (PCS) Mental Composite Score (MCS)

38.02 34.81

10.6 10.3

VR-36 subscales Physical Functioning Role—Physical Bodily Pain General Health Vitality Social Functioning Role—Emotional Mental Health

52.02 39.16 42.70 44.99 37.25 42.04 35.77 45.11

28.5 34.4 24.5 19.8 19.1 25.2 33.1 18.7

and two-way interactions were also non-significant and were removed, yielding a final model including only main effects. In the final model, there was a significant main effect of depressive symptoms on physical health-related quality of life (z = − 7.83, p b .001), meaning that across time those who reported fewer depressive symptoms reported better health-related quality of life, controlling for PTSD symptom severity and prolonged abstinence. The main effects for prolonged abstinence, time, period of service, and PCL-M total score were not statistically significant. The model is shown in Table 3. In terms of the VR-36 subscales, there were main effects for depression on Physical Functioning (z = −7.69, p b .001) and Role—Physical functioning (z = −13.19, p b .001). In the Role—Physical model, there was a main effect for period of service (z = 3.38, p = .001), meaning those who had a more recent period of service had less impairment in daily activities due to physical functioning. The main effects for prolonged abstinence, time, and PCL-M total score were not statistically significant. For the General Health subscale, while the four-way interaction was not significant, there was a significant two-way Time×PCL-M Total Score interaction (z=−4.06, pb .001), meaning those who reported a decrease in PTSD symptoms over time reported higher perceptions of overall health, self-ratings of health compared to others, and expectations about health in the future. The interaction is shown in Fig. 1. There were also main effects for depression (z=−12.66, pb .001) and prolonged abstinence (z=3.24, p= .001), meaning those who reported less depressive symptoms and those who quit smoking for 1 year reported better perceptions of general health. For the Bodily Pain subscale, the three-way and two-way interactions were not significant predictors. Therefore, they were removed from the model, and the main effects are reported. There were significant main effects of PTSD symptoms (z=−3.92, pb .001) and depressive symptoms (z=−8.51, pb .001) on pain, meaning those who reported fewer PTSD and depressive symptoms reported less pain. The main effects for prolonged abstinence, time, and period of service were not statistically significant. For the Vitality subscale, there was a significant PCL-M Total Score × PHQ-9 Total Score interaction (z = 3.85, p b .001), meaning those who reported fewer depressive and PTSD symptoms reported less fatigue. Fig. 2 shows the interaction graphically. There was also a significant two-way interaction between PTSD and depressive symptoms predicting Social Functioning (z = 2.97, p = .003), meaning those who reported fewer depressive and PTSD symptoms reported better social functioning. Fig. 3 shows the interaction graphically. There was a main effect of prolonged abstinence on Social Functioning (z = 2.88, p = .004), meaning those who reported 1 year of prolonged abstinence reported better social functioning.

Table 3 PA, PCL-M total score, and PHQ-9 total score predicting physical health-related quality of life Model: χ2(5) = 135.54, p b .001 Fixed effects

Coefficient

Standard error

z-Score

95% CI

Period of service PA Time PCL total PHQ-9 total

0.370 3.067 0.047 −0.015 −0.370

0.213 1.147 0.328 0.026 0.047

1.74 2.67 0.14 −0.59 −7.83⁎

−0.05, 0.79 0.82, 5.31 −0.69, 0.69 −0.07, 0.03 −0.46, −0.28

Random effects

SD

Standard error

95% CI

χ2

0.265 0.472

6.917, 7.956 0.483, 2.556

291.91⁎ –

Intercept Treatment site

7.418 1.111

CI=confidence interval; SD=standard deviation. A main effect indicates that the overall level of the predictor variable, which did not change significantly over time, was related to the overall score on the outcome variable, which also did not change over time. ⁎ p b .001

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Fig. 1. Time × PCL-M Total Score predicting General Health.

Discussion While our findings did not support our primary aim that quitting smoking in combination with improvement in psychiatric symptoms would be associated with changes in physical HRQoL, there were pertinent findings on the relation of PTSD and depressive symptoms to the HRQoL subscales. To date, findings on the role of co-morbid depression predicting HRQoL in PTSD samples have been inconsistent. In a model combining PTSD and depressive symptoms, we found that depression severity was the only significant predictor of physical HRQoL. However, when we examined the subscales, a different set of findings emerged. Depressive symptoms alone predicted the Physical Functioning and Role—Physical subscales. Depression and PTSD symptoms were independent predictors of the General Health and Bodily Pain subscales, but interacted to predict the Vitality and Social Functioning subscales. It appears that previous research findings may all be correct depending on how one interprets them. The Physical Functioning and Role—Physical subscales have the highest factor loadings on the Physical Component Summary. If those two subscales are most sensitive to depressive symptoms, it follows that studies, including ours, have found that depressive symptoms predict overall physical HRQoL, controlling for PTSD [43–45]. Depression has also previously been shown to account for poor Role—Physical functioning scores over PTSD symptoms [37], as we found here.

Fig. 2. PHQ-9 × PCL-M predicting Vitality.

Fig. 3. PHQ-9 × PCL-M predicting Social Functioning.

Our results suggest that both PTSD and depression are independently related to self-reported General Health and Bodily Pain, meaning high PTSD or high depression symptoms separately lead to poor health perceptions and greater pain. Additionally, there is an additive negative effect of the combination of PTSD and depressive symptoms on the Vitality and Social Functioning subscales, so that high levels of both PTSD and depression result in the greatest degree of impairment in energy level and social interaction. Our results seem to show that depression has an effect on objective physical functioning, for example, being able to walk a certain distance or being limited in daily activities due to physical impairment, which could be explained by some of the vegetative symptoms associated with depression. On the other hand, both high levels of PTSD and depressive symptoms resulted in a poor perception of health and greater experience of pain, both of which could be more closely categorized as sensory or subjective experiences of physical health. One study investigating the relationship between psychopathology and HRQoL lends some support to our findings. In this study, mood disorders were associated with global physical and mental health functional and role impairments, while anxiety disorders were more closely associated with social and mental health functioning impairments [65]. Anxiety, and particularly PTSD, has demonstrated a strong association with the experience of pain [66]. Heightened pain sensitivity, which is related to high levels of anxiety sensitivity, may be a particularly important factor in individuals with PTSD [67,68]. Depression and pain also have a well-established relationship, however, some gender differences have been noted; women have a higher rate of co-morbid depression and pain, and the experience of pain for women seems to be related to pain report and sensitivity, while for men it has been largely related to functional impairment [69,70]. Our study sample was largely comprised of men, and physical and role—physical functional impairment was related to depressive symptom severity score. Our findings did not confirm our primary aim that quitting smoking in combination with improvements in PTSD and depressive symptoms would predict changes in HRQoL. There are several plausible explanations for the discrepancy. Only 63 study participants met the conservative PA criteria of yearlong, bio-verified cessation without relapse. Quit rates in our sample reflect previously published research that shows that individuals with psychiatric disorders, including PTSD and depression, have substantially lower quit rates than their non-psychiatric counterparts [21,71,72]. Prolonged abstinence was associated with higher scores on two of the six VR-36 subscales, General Health and Social Functioning. Findings related to improvement in health perceptions post smoking cessation are mixed with evidence for [50,73] and against [74,75] an effect of quitting smoking on self-perceived health status. One study reported no improvements in social functioning

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across quitters [74], but in another study that included some patients with depression, smoking was related to poorer social functioning on the SF-36 [76]. It is possible that discrepancies may be due to the fact that smoking is one of a number of health-risk factors that affect HRQoL, and it may be difficult to isolate its independent effect. Our findings suggest that quitting for 1 year may be associated with improved self-perceptions of health and social functioning when PTSD and depression are included in the model. However, it cannot be inferred whether individuals who quit smoking are more likely to quit if they have high pre-morbid HRQoL scores, or whether quitting predicts improvement in HRQoL. Our study has several limitations. Most of the data were collected via self-report. However, smoking cessation was bio-verified and both interviewer-assisted and self-report measures were used to evaluate PTSD symptoms, and the two were largely comparable. Additionally, due to the low quit rate, power to detect significant differences may have been limited, especially with the use of higher order interaction terms. The sample consisted of treatment-seeking veterans enrolled in VA healthcare, most of whom were Vietnam era veterans. The sample may not be representative of all veterans or non-veterans. The sample had a high level of medical and psychiatric impairments, which may limit the generalizability of the findings, and may have affected the degree of change in symptom scores over time (i.e., HRQoL may not improve with multiple medical co-morbidities despite improvement in psychiatric symptoms and quitting smoking).

Conclusion Our findings provide further evidence of a strong relationship between PTSD, depression, tobacco dependence, and poor physical HRQoL. Depressive and PTSD symptoms differentially affected the physical HRQoL subscales, and looking at the omnibus effects of PTSD and depression on physical HRQoL may lead to the exclusion of important information about the differential effects of PTSD and depressive symptoms on HRQoL. If PTSD and depressive symptomatology are both largely responsible for poor quality of life, it may be wise to consider addressing them in concert. In our study, participants in both the experimental and non-experimental treatment groups were receiving individual and sometimes group PTSD treatment, an inclusion criterion for the study. Psychotherapeutic treatment for depression was not explicitly provided though most participants were on antidepressant medications throughout the study. At post-treatment, mean PTSD symptoms were reduced in both treatment groups, but depressive symptoms were unchanged [47]. It is plausible that lack of treatment for depression inhibited improvements in physical HRQoL over time. Type of PTSD treatment received was not controlled for as part of this trial, and there is research showing that exposure therapies for PTSD can improve depressive symptoms [32,33]. Participants in this trial may or may not have received exposure therapy as part of treatment. It is important to ensure that treatments for PTSD also target, or at least simultaneously improve, symptoms of depression, especially if HRQoL is an outcome variable for PTSD or depression treatment. The impact of PTSD and depression on both physical and mental health, and the high incidence rate of co-occurring addictive disorders, including tobacco dependence, may suggest the utility of an integrated approach. Promising integrated care approaches have been implemented in the VA system to target co-morbid psychiatric and substance use disorders [47,77]. Additionally, exposure therapies for PTSD have been utilized in patients with co-occurring substance use with some preliminary success [78,79]. To date, head-to-head trials comparing integrated treatments with treatments delivered separately appear to be limited. It may be important to conduct such research to better assist the newly returning veteran population that is struggling at high rates with depression and substance use disorders in addition to PTSD symptoms [80,81].

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Acknowledgments Funding was provided by the Cooperative Studies Program of the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs (DVA) (CSP #519, NCT00118534) and the Tobacco-Related Disease Research Program 19DT-0003. Dr. Baker receives research support from the Department of Defense (Navy BUMED and CDMRP) (PTO 090738) and the DVA HSR&D (SDR09-128) and is supported in part by the VA Center of Excellence for Stress and Mental Health. Dr. McFall receives research support from VA Merit #821 and DVA. Dr. Saxon receives research support from NIAAA (1 P20 AA017839-01), NIDA (5 U10 DA013714-08), and from VA HSR&D (1 IO1 HX000616-01). The views expressed herein are those of the authors and not necessarily those of the U.S. Department of Veterans Affairs. The authors have no competing interests to report.

References [1] Kang HK, Bullman TA, Taylor JW. Risk of selected cardiovascular diseases and posttraumatic stress disorder among former World War II prisoners of war. Ann Epidemiol May 2006;16:381–6. [2] American Lung Association. Trends in tobacco use; 2010. [3] Boscarino JA. Posttraumatic stress disorder and mortality among U.S. Army veterans 30 years after military service. Ann Epidemiol Apr 2006;16:248–56. [4] Carney RM, Freedland KE. Depression, mortality, and medical morbidity in patients with coronary heart disease. Biol Psychiatry Aug 1 2003;54:241–7. [5] Chen TH, Li L, Kochen MM. A systematic review: how to choose appropriate health-related quality of life (HRQOL) measures in routine general practice? J Zhejiang Univ Sci B Sep 2005;6:936–40. [6] Kaplan RM. Behavior as the central outcome in health care. Am Psychol Nov 1990;45:1211–20. [7] Kaplan RM, Bush JW, Berry CC. Health status: types of validity and the index of well-being. Health Serv Res Winter 1976;11:478–507. [8] Sprenkle MD, Niewoehner DE, Nelson DB, Nichol KL. The Veterans Short Form 36 questionnaire is predictive of mortality and health-care utilization in a population of veterans with a self-reported diagnosis of asthma or COPD. Chest Jul 2004;126:81–9. [9] Bosworth HB, Siegler IC, Brummett BH, Barefoot JC, Williams RB, Clapp-Channing NE, et al. The association between self-rated health and mortality in a well-characterized sample of coronary artery disease patients. Med Care Dec 1999;37:1226–36. [10] Konstam V, Salem D, Pouleur H, Kostis J, Gorkin L, Shumaker S, et al. Baseline quality of life as a predictor of mortality and hospitalization in 5,025 patients with congestive heart failure. SOLVD Investigations. Studies of Left Ventricular Dysfunction Investigators. Am J Cardiol Oct 15 1996;78:890–5. [11] Rumsfeld JS, MaWhinney S, McCarthy M, Shroyer AL, VillaNueva CB, O'Brien M, et al. Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the Department of Veterans Affairs Cooperative Study Group on processes, structures, and outcomes of care in cardiac surgery. JAMA Apr 14 1999;281:1298–303. [12] Tibblin G, Svardsudd K, Welin L, Erikson H, Larsson B. Quality of life as an outcome variable and a risk factor for total mortality and cardiovascular disease: a study of men born in 1913. J Hypertens Suppl Jun 1993;11:S81–6. [13] Tsai SY, Chi LY, Lee C, Chou P. Health-related quality of life as a predictor of mortality among community-dwelling older persons. Eur J Epidemiol 2007;22:19–26. [14] Mapes DL, Lopes AA, Satayathum S, McCullough KP, Goodkin DA, Locatelli F, et al. Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Kidney Int Jul 2003;64: 339–49. [15] Domingo-Salvany A, Lamarca R, Ferrer M, Garcia-Aymerich J, Alonso J, Felez M, et al. Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med Sep 1 2002;166:680–5. [16] Jiang Y, Hesser JE. Associations between health-related quality of life and demographics and health risks. Results from Rhode Island's 2002 behavioral risk factor survey. Health Qual Life Outcomes 2006;4:14. [17] Buckley TC, Mozley SL, Bedard MA, Dewulf AC, Greif J. Preventive health behaviors, health-risk behaviors, physical morbidity, and health-related role functioning impairment in veterans with post-traumatic stress disorder. Mil Med Jul 2004;169: 536–40. [18] Jakupcak M, Luterek J, Hunt S, Conybeare D, McFall M. Posttraumatic stress and its relationship to physical health functioning in a sample of Iraq and Afghanistan War veterans seeking postdeployment VA health care. J Nerv Ment Dis May 2008;196:425–8. [19] Schnurr PP, Spiro A. Combat exposure, posttraumatic stress disorder symptoms, and health behaviors as predictors of self-reported physical health in older veterans. J Nerv Ment Dis Jun 1999;187:353–9. [20] Gaynes BN, Burns BJ, Tweed DL, Erickson P. Depression and health-related quality of life. J Nerv Ment Dis Dec 2002;190:799–806. [21] Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: a population-based prevalence study. JAMA Nov 22–29 2000;284:2606–10.

190

L.H. Aversa et al. / Journal of Psychosomatic Research 73 (2012) 185–190

[22] Center for Disease Control and Prevention. National health interview survey; 2008. [23] Nelson JP, Pederson LL. Military tobacco use: a synthesis of the literature on prevalence, factors related to use, and cessation interventions. Nicotine Tob Res May 2008;10:775–90. [24] DiNicola AF, Sarrett DA, Parra LJ, Nissen KT, Wilkens SC. RE: tobacco product usage in Afghanistan: deployed military personnel versus deployed civilian contractors. Mil Med May 2011;176:iii. [25] Brown TA, Campbell LA, Lehman CL, Grisham JR, Mancill RB. Current and lifetime comorbidity of the DSM-IV anxiety and mood disorders in a large clinical sample. J Abnorm Psychol Nov 2001;110:585–99. [26] Keane TM, Kaloupek DG. Comorbid psychiatric disorders in PTSD. Implications for research. Ann N Y Acad Sci Jun 21 1997;821:24–34. [27] Keane TM, Wolfe J. Comorbidity in post-traumatic stress disorder: an analysis of community and clinical studies. J Appl Soc Psychol 1990;20:1776–88. [28] Brady KT, Killeen TK, Brewerton T, Lucerini S. Comorbidity of psychiatric disorders and posttraumatic stress disorder. J Clin Psychiatry 2000;61:22–32. [29] Shalev AY, Freedman S, Peri T, Brandes D, Sahar T, Orr SP, et al. Prospective study of posttraumatic stress disorder and depression following trauma. Am J Psychiatry May 1998;155:630–7. [30] Brady KT, Clary CM. Affective and anxiety comorbidity in post-traumatic stress disorder treatment trials of sertraline. Compr Psychiatry Sep-Oct 2003;44:360–9. [31] Zayfert C, Becker CB, Unger DL, Shearer DK. Comorbid anxiety disorders in civilians seeking treatment for posttraumatic stress disorder. J Trauma Stress Feb 2002;15:31–8. [32] Foa EB, Dancu CV, Hembree EA, Jaycox LH, Meadows EA, Street GP. A comparison of exposure therapy, stress inoculation training, and their combination for reducing posttraumatic stress disorder in female assault victims. J Consult Clin Psychol Apr 1999;67:194–200. [33] Marks I, Lovell K, Noshirvani H, Livanou M, Thrasher S. Treatment of posttraumatic stress disorder by exposure and/or cognitive restructuring: a controlled study. Arch Gen Psychiatry Apr 1998;55:317–25. [34] Paunovic N, Ost LG. Cognitive-behavior therapy vs exposure therapy in the treatment of PTSD in refugees. Behav Res Ther Oct 2001;39:1183–97. [35] Feeny N, Hembree EA, Zoellner L. Myths regarding exposure therapy for PTSD. Cogn Behav Pract 2003;10:85–90. [36] Richardson JD, Long ME, Pedlar D, Elhai JD. Posttraumatic stress disorder and health-related quality of life among a sample of treatment- and pension-seeking deployed Canadian Forces peacekeeping veterans. Can J Psychiatry Sep 2008;53: 594–600. [37] Ouimette P, Cronkite R, Henson BR, Prins A, Gima K, Moos RH. Posttraumatic stress disorder and health status among female and male medical patients. J Trauma Stress Feb 2004;17:1–9. [38] Rapaport MH, Clary C, Fayyad R, Endicott J. Quality-of-life impairment in depressive and anxiety disorders. Am J Psychiatry Jun 2005;162:1171–8. [39] Zayfert C, Dums AR, Ferguson RJ, Hegel MT. Health functioning impairments associated with posttraumatic stress disorder, anxiety disorders, and depression. J Nerv Ment Dis Apr 2002;190:233–40. [40] Frayne SM, Seaver MR, Loveland S, Christiansen CL, Spiro A, Parker VA, et al. Burden of medical illness in women with depression and posttraumatic stress disorder. Arch Intern Med Jun 28 2004;164:1306–12. [41] Ikin JF, Creamer MC, Sim MR, McKenzie DP. Comorbidity of PTSD and depression in Korean War veterans: prevalence, predictors, and impairment. J Affect Disord Sep 2010;125:279–86. [42] Mittal D, Fortney JC, Pyne JM, Edlund MJ, Wetherell JL. Impact of comorbid anxiety disorders on health-related quality of life among patients with major depressive disorder. Psychiatr Serv Dec 2006;57:1731–7. [43] Rauch SA, Morales KH, Zubritsky C, Knott K, Oslin D. Posttraumatic stress, depression, and health among older adults in primary care. Am J Geriatr Psychiatry Apr 2006;14: 316–24. [44] Pittman JO, 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 Apr 2011;21:99–103. [45] Goenjian AK, Roussos A, Steinberg AM, Sotiropoulou C, Walling D, Kakaki M, et al. Longitudinal study of PTSD, depression, and quality of life among adolescents after the Parnitha earthquake. J Affect Disord Oct 2011;133:509–15. [46] Osthus T, Dammen T, Sandvik L, Bruun C, Nordhus I, Os I. Health-related quality of life and depression in dialysis patients: associations with current smoking. Scand J Urol Nephrol 2010;44:46–55. [47] McFall M, Saxon AJ, Malte CA, Chow B, Bailey S, Baker DG, et al. Integrating tobacco cessation into mental health care for posttraumatic stress disorder: a randomized controlled trial. JAMA Dec 8 2010;304:2485–93. [48] Mulder I, Tijhuis M, Smit HA, Kromhout D. Smoking cessation and quality of life: the effect of amount of smoking and time since quitting. Prev Med Dec 2001;33:653–60. [49] Sarna L, Bialous SA, Cooley ME, Jun HJ, Feskanich D. Impact of smoking and smoking cessation on health-related quality of life in women in the Nurses' Health Study. Qual Life Res Dec 2008;17:1217–27. [50] Tillmann M, Silcock J. A comparison of smokers' and ex-smokers' health-related quality of life. J Public Health Med Sep 1997;19:268–73. [51] Elliott AJ, Russo J, Roy-Byrne PP. The effect of changes in depression on health related quality of life (HRQoL) in HIV infection. Gen Hosp Psychiatry Jan-Feb 2002;24:43–7. [52] ten Doesschate MC, Koeter MW, Bockting CL, Schene AH. Health related quality of life in recurrent depression: a comparison with a general population sample. J Affect Disord Jan 2010;120:126–32.

[53] Schnurr PP, Hayes AF, Lunney CA, McFall M, Uddo M. Longitudinal analysis of the relationship between symptoms and quality of life in veterans treated for posttraumatic stress disorder. J Consult Clin Psychol Aug 2006;74:707–13. [54] Kazis LE, Lee A, Spiro A, Rogers W, Ren XS, Miller DR, et al. Measurement comparisons of the medical outcomes study and veterans SF-36 health survey. Health Care Financ Rev Summer 2004;25:43–58. [55] Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, et al. The development of a clinician-administered PTSD scale. J Trauma Stress Jan 1995;8:75–90. [56] Blanchard EB, Jones-Alexander J, Buckley TC, Forneris CA. Psychometric properties of the PTSD Checklist (PCL). Behav Res Ther Aug 1996;34:669–73. [57] Weathers F, Litz B, Herman D, Huska J, Keane T. The PTSD Checklist (PCL): reliability, validity, and diagnostic utility. Paper presented at the Annual Convention of the International Society for Traumatic Stress Studies. San Antonio, TX: International Society for Traumatic Stress Studies; 1993. [58] Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med Sep 2001;16:606–13. [59] Department of Veterans Affairs. Veteran population. Available from: http://www. va.gov/vetdata/. [60] Weathers FW, Ruscio AM, Keane TM. Psychometric properties of nine scoring rules for the clinician-administered posttraumatic stress disorder scale. Psychol Assess 1999;11:124–33. [61] King DW, Leskin GA, King LA, Weathers FW. Confirmatory factor analysis of the clinician-administered PTSD Scale: evidence for the dimensionality of posttraumatic stress disorder. Psychol Assess 1998;10:90–6. [62] Prins A, Kimerling R, Yeager DE, Magruder KM. Guidelines for interpreting PCL scores in VA settings: an interval approach; 2010. [63] 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 Nov 10 1999;282:1737–44. [64] Ware JE, Kosinski M, Gandek B. SF-36 health survey: manual and interpretation guide. Lincoln, RI: QualityMetric Incorporated; 2005. [65] Spitzer RL, Kroenke K, Linzer M, Hahn SR, Williams JB, deGruy FV, et al. Health-related quality of life in primary care patients with mental disorders. Results from the PRIME-MD 1000 study. JAMA Nov 15 1995;274:1511–7. [66] Asmundson GJ, Abrams MP, Collimore KC. Pain and anxiety disorders. In: Zvolensky MJ, Smits JA, editors. Anxiety in health behaviors and physical illness. New York: Springer; 2008. p. 207–36. [67] Asmundson GJ, Katz J. Understanding pain and posttraumatic stress disorder comorbidity: do pathological responses to trauma alter the perception of pain? Pain Aug 31 2008;138:247–9. [68] Asmundson GJ, Katz J. Understanding the co-occurrence of anxiety disorders and chronic pain: state-of-the-art. Depress Anxiety 2009;26:888–901. [69] Haley WE, Turner JA, Romano JM. Depression in chronic pain patients: relation to pain, activity, and sex differences. Pain Dec 1985;23:337–43. [70] Smith GR. The epidemiology and treatment of depression when it coexists with somatoform disorders, somatization, or pain. Gen Hosp Psychiatry Jul 1992;14:265–72. [71] Dierker LC, Avenevoli S, Merikangas KR, Flaherty BP, Stolar M. Association between psychiatric disorders and the progression of tobacco use behaviors. J Am Acad Child Adolesc Psychiatry Oct 2001;40:1159–67. [72] Hughes JR. Comorbidity and smoking. Nicotine Tob Res 1999;1:S149–52 [discussion S65-6]. [73] Colsher PL, Wallace RB, Pomrehn PR, LaCroix AZ, Cornoni-Huntley J, Blazer D, et al. Demographic and health characteristics of elderly smokers: results from established populations for epidemiologic studies of the elderly. Am J Prev Med Mar-Apr 1990;6:61–70. [74] Stewart AL, King AC, Killen JD, Ritter PL. Does smoking cessation improve health-related quality of life. Ann Behav Med 1995;17:331–8. [75] Taira DA, Seto TB, Ho KK, Krumholz HM, Cutlip DE, Berezin R, et al. Impact of smoking on health-related quality of life after percutaneous coronary revascularization. Circulation Sep 19 2000;102:1369–74. [76] Duffy SA, Terrell JE, Valenstein M, Ronis DL, Copeland LA, Connors M. Effect of smoking, alcohol, and depression on the quality of life of head and neck cancer patients. Gen Hosp Psychiatry May-Jun 2002;24:140–7. [77] Najavits LM, Weiss RD, Shaw SR, Muenz LR. “Seeking safety”: outcome of a new cognitive–behavioral psychotherapy for women with posttraumatic stress disorder and substance dependence. J Trauma Stress Jul 1998;11:437–56. [78] Back SE, Dansky BS, Carroll KM, Foa EB, Brady KT. Exposure therapy in the treatment of PTSD among cocaine-dependent individuals: description of procedures. J Subst Abuse Treat Jul 2001;21:35–45. [79] Berenz EC, Rowe L, Schumacher JA, Stasiewicz PR, Coffey SF. Prolonged exposure therapy for PTSD among individuals in a residential substance use treatment program: a case series. Prof Psychol Res Pract Apr 1 2012;43:154–61. [80] Knobloch LK, Theiss JA. Depressive symptoms and mechanisms of relational turbulence as predictors of relationship satisfaction among returning service members. J Fam Psychol Aug 2011;25:470–8. [81] Seal KH, Bertenthal D, Miner CR, Sen S, Marmar C. Bringing the war back home: mental health disorders among 103,788 US veterans returning from Iraq and Afghanistan seen at Department of Veterans Affairs facilities. Arch Intern Med Mar 12 2007;167:476–82.