Metabolic Syndrome: Relative Risk Associated with Post-Traumatic Stress Disorder (PTSD) Severity and Antipsychotic Medication Use

Psychosomatics 2012:53:550 –558

Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.

Original Research Reports Metabolic Syndrome: Relative Risk Associated with Post-Traumatic Stress Disorder (PTSD) Severity and Antipsychotic Medication Use Pia S. Heppner, Ph.D., James B. Lohr, M.D., Taylor P. Kash, M.P.H., Hua Jin, M.D., Hongjun Wang, Ph.D., Dewleen G. Baker, M.D.

Background: In recent years, numerous lines of converging evidence have revealed an association between post-traumatic stress disorder (PTSD) and impaired physical health outcomes, including cardiovascular disease and metabolic syndrome. Although these findings have been interpreted as indicating a direct association of PTSD with metabolic syndrome and obesity, previous studies have not addressed the important confound of antipsychotic drug usage in this population. Second generation antipsychotic medications themselves are associated with metabolic syndrome and obesity, and it is unclear whether the common utilization of these drugs in PTSD may account for some if not all of the observed metabolic problems. Objective: The present study examined the relative contributions of PTSD severity and use of antipsychotic medications to risk of metabolic syndrome among veterans. Method: Cross-sectional clinical data, including five factors

representing metabolic syndrome, psychiatric diagnoses, and medications were gathered from 253 veterans enrolling in mental health services. We used a logistic regression model to measure the relative association of antipsychotic medication use and PTSD severity on risk of metabolic syndrome. Results: We found that antipsychotic medication usage was not uniquely associated with elevated risk of metabolic syndrome (Wald ⫽ 0.30, ns) when PTSD severity and other sociodemographic, psychiatric, and behavioral variables were accounted for. Furthermore, PTSD severity continued to be a significant and unique predictor of risk for metabolic syndrome (Wald ⫽ 4.04, p ⬍ 0.05). Conclusions: These findings suggest that chronic and moderately severe PTSD, independent of antipsychotic medications, is associated with increased risk of metabolic syndrome. (Psychosomatics 2012; 53:550 –558)

I

Using cohort data from the Normative Aging Study, these investigators found that a one standard deviation increase

n the past decade there, has been a growing body of research demonstrating the impact of post-traumatic stress disorder (PTSD) on physical health. In particular, epidemiologic and clinical studies have highlighted an association between PTSD and cardiovascular risk factors, including obesity, hypertension, and diabetes mellitus.1– 6 Two recent prospective studies using large samples of veterans without pre-existing heart disease observed increased risk of heart disease-related morbidity and mortality.7,8 Kubzansky and colleagues observed that not only the presence of PTSD, but the severity of PTSD was important in predicting later cardiovascular outcomes.7 550

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Received January 20, 2012; revised May 15, 2012; accepted May 17, 2012. From the Veterans Affairs San Diego Healthcare System, San Diego, CA (PSH, JBL, TPK, HJ, DGB); Department of Psychiatry, University of California, San Diego, CA (PSH, JBL, DGB); VA Center of Excellence for Stress and Mental Health, San Diego, CA (JBL, HJ, HW, DGB). Send correspondence and reprint requests to Dewleen G. Baker, M.D., VA Center of Excellence for Stress and Mental Health (116A), VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161; e-mail: [email protected] Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.

Psychosomatics 53:6, November-December 2012

Heppner et al. in symptom level on two different measures of self-reported PTSD was associated with age-adjusted relative risks of 1.21–1.26 of developing myocardial infarction and angina among male veterans within an 11- to 15-year period following initial assessment of PTSD. Boscarino examined early-age (under 65) heart disease-related mortality among Vietnam era veterans within a 15-year follow-up period. Veterans with PTSD, as identified using the Keane PTSD Scale or a DSM-III based measure of PTSD, were significantly more likely to die of heart disease before the age of 65 compared with those without PTSD (hazard ratio 2.16 –2.25).8 However, these studies observed low rates of PTSD, with only 1% of the total sample (n ⫽ 1946) in the Normative Aging Study and 6% in the study by Boscarino meeting cutoff scores for PTSD. In our recent previous study of 253 treatment-seeking veterans, we found that severity of PTSD was associated with a greater likelihood of meeting criteria for metabolic syndrome.9 Metabolic syndrome is a known risk factor for later cardiovascular disease and diabetes mellitus.10,11 The syndrome consists of dyslipidemia, hyperglycemia (insulin resistance), central adiposity, and hypertension.12 Forty percent of the sample met criteria for metabolic syndrome compared with the observed prevalence of metabolic syndrome in the general population of 22% (24% adjusting for age).13 After controlling sociodemographic factors, as well as psychiatric and behavioral variables (depression, alcohol, substance and nicotine abuse or dependence), the relationship between higher PTSD severity and increased risk for metabolic syndrome status appeared to be maintained. Several, but not all, studies have also observed similar findings of an association between PTSD and metabolic syndrome risk. Among Croatian combat veterans with PTSD, the rates of metabolic syndrome were higher compared with a nonclinical sample (32% vs. 9%).14 Moreover, rates were higher among the subsample with greater PTSD symptom severity (67%) compared with those with lower severity symptoms (23%).15 Violanti and colleagues reported a very similar finding in a study of police officers where the prevalence of metabolic syndrome was 50% among those with severe PTSD, compared with only 15% among those who did not meet the clinical threshold for diagnosis of PTSD.16 A recent study found an association between health care quality of life and PTSD in aging former refugee children, but not between PTSD and various metabolic syndrome variables, although it appears that rather than using criteria from the National Cholesterol Education Panel (NCEP) or National Health and Psychosomatics 53:6, November-December 2012

Nutrition Examination Survey (NHANES) criteria, each variable and its relation to PTSD were analyzed separately.17 Although a number of study results are very suggestive of a direct association of PTSD with metabolic syndrome, there is a very important confound, which has not been specifically addressed in previous studies—the growing use of second generation antipsychotic medications. It has become clear in the past decade that these medications, including drugs such as olanzapine and risperidone, can cause metabolic syndrome, and that this has become a very important problem in the treatment of psychosis.18 –20 However, these drugs are also commonly used to treat many other conditions, including such on-label conditions as depression and, relevant to the present study, off-label indications such as PTSD. Although the evidence base for the use of antipsychotic medications for symptoms of PTSD is at best inconsistent, the off-label use of antipsychotic medications for PTSD is nevertheless widespread.21,22 Using a sample of 279,778 veterans identified as having at least one prescribed antipsychotic medication in 2007, Leslie and colleagues observed that PTSD was the most common psychiatric diagnosis among patients for whom off-label use of antipsychotic medications was prescribed (42%), followed by minor depression (40%), major depression (23%), and anxiety disorder (20%).23 Therefore, it is unclear to what extent the connection between PTSD and metabolic syndrome reported in other studies may, in fact, be due to the utilization of these drugs in this population. Given the higher rates of metabolic syndrome observed among cohorts with higher levels of PTSD and the common use of antipsychotic medications in the therapy of this chronic psychiatric disorder, the following study was designed to determine the relative contributions of PTSD severity and of antipsychotic medication use to metabolic syndrome status in a veteran sample. METHODS Participants Three hundred fifty-five male and female veterans who were being seen as outpatients completed comprehensive medical and mental health examinations from 2000 to 2003 upon entering Gulf War Screening and PTSD Programs at the Cincinnati Veterans Affairs. Medical examinations were performed by nurse practitioners, while mental health assessments were completed by liwww.psychosomaticsjournal.org

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Metabolic Syndrome Risk: PTSD, Antipsychotic Meds censed mental health clinicians trained in administering structured psychodiagnostic interviews (psychologists and social workers). Assessments were jointly discussed by clinical staff in group consultation. After a complete description of the study to participants, written consent was obtained from 341 participants permitting use of their data for a health-related study. The study was conducted in accordance with the Helsinki Declaration, and was approved by the University of California, San Diego Institutional Review Board and the Veterans Affairs San Diego Health Services Research and Development Committee (protocol no. 091360; “Post-traumatic Stress Disorder and Physical and Psychological Outcomes in Post-deployment Veterans”). Of the 341 consenting veterans, we excluded 69 veterans who had missing data from one or more variables of interest, and we also excluded 19 veterans (including one who also had missing data) whose laboratory values were greater than three standard deviations (SDs) from the group mean. Exclusion of cases with extreme laboratory values allowed for a more conservative analysis of quantitative physiological burden. These exclusions yielded a remaining 253 male and female veterans.

Measures Sociodemographics Sociodemographic information was collected through written questionnaires and included years of education, military service, and deployment history. Psychiatric Diagnoses PTSD severity was measured using the clinician-administered PTSD scale (CAPS), in which scores can range from 0 to 136.24 A score of 65 has been shown to be optimally specific and efficient in predicting PTSD and was used to identify veterans with PTSD.25 Lifetime and current diagnoses of major depressive disorder (MDD), psychotic disorder, and nicotine, substance, and alcohol abuse/dependence were determined using a structured diagnostic interview.26,27 Psychotropic Medication Information concerning current psychotropic medication usage was obtained from all participants by interview and chart review. 552

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Physical Measures Physical examinations including waist-to-hip ratio (WHR), blood pressure and laboratory tests (12-hour fasting for lipids and glucose) were conducted on each veteran. Phlebotomy was scheduled between 7 and 9 am. All samples were assayed within the hospital clinical laboratory. Procedure Using a cross-sectional design, all data were gathered upon enrolment for mental health services. Metabolic syndrome status was determined using clinical criteria for serum triglycerides, high density lipoprotein (HDL), systolic and diastolic blood pressure (SBP and DBP), waist-to-hip ratio (WHR), and plasma glucose concentration. Cutoff scores for each of the five factors were previously described in our earlier investigation relating PTSD and metabolic syndrome in the same sample of veterans and were defined as follows: (1) serum triglycerides ⬎150 mg/dL, (2) HDL ⬍35 mg/dL, (3) SBP ⱖ130 mm/Hg, and DBP ⱖ85 mm/Hg, (4) WHR ⱖ 0.90 for men and ⱖ 0.85 for women, and plasma glucose concentration ⱖ110 mg/dL.9 SBP and DBP values were combined to represent hypertension yielding a total of five criteria that contributed to metabolic syndrome. While the cut-off score for elevated serum triglycerides was based on NCEP criteria, increased blood pressure, HDL, WHR, and plasma glucose concentration were based on a modified set of criterion scores recommended by the World Health Organization (WHO) and the NCEP, similar to those used by Lakka and colleagues to evaluate CVD-related mortality and metabolic syndrome.28 –30 Statistical Analyses We used a logistic regression model that included sociodemographic and psychiatric variables as well as antipsychotic medication use in order to predict presence/absence of metabolic syndrome. Statistical analyses were conducted using SPSS ver. 15.0. (SPSS Inc., Chicago, IL). Predictors used to determine metabolic syndrome status were: PTSD severity (CAPS score), age, gender, race (white, black/other), years of education, substance abuse/dependence (lifetime), alcohol abuse/dependence (lifetime), nicotine abuse/dependence (lifetime), and current or past diagnosis of MDD. Psychosomatics 53:6, November-December 2012

Heppner et al. All predictors were entered simultaneously into the regression model within a single block. Analyses comparing groups (with vs. without antipsychotic medication use) on sociodemographic, psychiatric, and medical variables were conducted using ␹2 tests (for categorical variables) and independent samples t-tests (for continuous variables). Given the lack of comparable sample sizes, 33 (13%) vs. 220 (87%), of the two groups with and without antipsychotic medications, we ran a series of bootstrap analyses with 1000 replications of the logistic regression model using a 24 (30%) vs. 56 (70%) re-sampling (with replacement) method. Specifically, we reconstructed a sample of 24 subjects randomly selected with replacement from the antipsychotic medication group and 56 subjects randomly selected with replacement from the without antipsychotic medication group. Using each set of derived 24 (30%) and 56 (70%) samples, a logistic regression was performed. This process was repeated 1000 times so that the frequency (percentage of times) of each variable being significant (at the 0.05 level) in the logistic regression could be calculated. RESULTS Participants The sociodemographic and psychiatric characteristics of the sample are listed in Tables 1 and 2. The sample was primarily male and white, with an average age of 52 ⫾ 9 years. A large proportion served in the U.S. Army and more than 70% served in Vietnam. Over half of the veterans met criteria for PTSD (as defined by a CAPS score of more than 65) and close to two-thirds of the participants met criteria for MDD. Smoking was also highly prevalent, with 40% of the sample identified as current smokers. Almost 40% of the sample met criteria for lifetime non-alcohol substance abuse or dependence and almost 70% for met criteria for lifetime alcohol abuse or dependence. Additionally, there was high comorbidity between PTSD, and MDD, lifetime nicotine, substance and alcohol abuse, or dependence. Mean values for physical and laboratory measures for the overall sample as well as for subsamples with and without antipsychotic medication use are shown in Table 3. Almost three-quarters (73%) of the sample were either overweight (body mass index or body mass index (BMI) ⫽ 25–30) or obese (BMI ⱖ30). On averPsychosomatics 53:6, November-December 2012

TABLE 1.

Sociodemographic Characteristics of Veterans (n ⴝ 253) Without With All Veterans Antipsychotic Antipsychotic Sig. (p) (n ⴝ 253) Medications Medications (n ⴝ 220) (n ⴝ 33)

Continuous variables Age in years Years of education Categorical variables Male Race White Black Other Branch of service Army Marines Navy Air force Service era World War II Korea Vietnam Gulf War I Other conflicts

Mean (SD)

Mean (SD)

Mean (SD)

51.5 (9.0) 12.9 (2.4)

51.8 (9.1) 12.9 (2.4)

48.9 (7.6) 13 (2.4)

No. (%)

No. (%)

No. (%)

233 (92)

203 (92)

30 (91)

193 (76) 47 (19) 13 (5)

172 (78) 39 (18) 9 (4)

21 (64) 8 (24) 4 (12)

ns ns

ns ns

ns 153 (60) 53 (21) 26 (10) 21 (8)

130 (59) 48 (22) 23 (10) 19 (9)

23 (70) 5 (15) 3 (9) 2 (6)

7 (3) 8 (3) 180 (71) 36 (14) 22 (9)

7 (3) 8 (4) 154 (70) 33 (15) 18 (8)

0 (0) 0 (0) 26 (79) 3 (9) 4 (12)

ns

ns ⫽ no significance.

age, the sample had elevated serum triglycerides, high total cholesterol/HDL ratios, and central obesity. Metabolic Syndrome Status One hundred one veterans (40%) met criteria for metabolic syndrome. Seventy-eight veterans (31%) met criteria for elevated blood pressure (both SBP at least 130 mm/Hg and DBP at least 85 mm/Hg). One hundred twenty-nine veterans (51%) met metabolic syndrome criteria for elevated triglycerides. Twenty-five percent of the sample met metabolic syndrome criteria for low HDL (⬍35 mg/dL). Sixty-seven veterans (27%) met criteria for elevated glucose levels (at least 110 mg/dL). Finally, 85% (215 veterans) met criteria abdominal obesity (WHR at least 0.9 for men and 0.85 for women). Table 3 details group differences in metabolic syndrome parameters by antipsychotic medication status. No significant group differences were observed with regard to BMI, triglycerides, HDL, blood pressure, central obesity, or fasting serum glucose levels. www.psychosomaticsjournal.org

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TABLE 2.

Psychiatric Characteristics of Veterans (n ⴝ 253)

Antipsychotic medication use Risperdal Quetiapine Olanzapine Psychiatric diagnoses CAPSa score, Mean, (SD) PTSD At least moderate severityb Psychotic disorder MDDc Nicotine abuse/dependence (lifetime) Non-alcohol substance abuse/dependence (lifetime) Alcohol abuse/dependence (lifetime) Comorbidities with PTSDb PTSD and psychotic disorder PTSD and MDDc PTSD and lifetime nicotine abuse/dependence PTSD and lifetime substance abuse/dependence PTSD and lifetime alcohol abuse/dependence

All Veterans (n ⴝ 253) No. (%)

Without Antipsychotic Medications (n ⴝ 220) No. (%)

With Antipsychotic Medications (n ⴝ 33) No. (%)

Sig. (p)

10 (4) 13 (5) 10 (4)

n/a n/a n/a

10 (30) 13 (39) 10 (30)

n/a n/a n/a

62.8 (29.4)

60.4 (29.9)

78.7 (19.7)

139 (55) 13 (5) 163 (64) 98 (39) 102 (40) 174 (69)

115 (52) 4 (2) 146 (66) 89 (41) 82 (37) 153 (70)

24 (73) 9 (27) 17 (52) 9 (27) 20 (61) 21 (64)

0.028 ⬍0.001 ns ns 0.011 ns

9 (4) 104 (41) 53 (21) 67 (26) 107 (42)

4 (2) 90 (41) 46 (21) 51 (23) 90 (41)

5 (15) 14 (42) 7 (21) 16 (49) 17 (52)

⬍0.001 ns ns 0.002 ns

0.001

ns ⫽ no significance; PTSD ⫽ post traumatic stress disorder; SD ⫽ standard deviation. a Clinician-administered PTSD scale (CAPS). b At least moderate PTSD (CAPS ⬎ 65). c Diagnosis of major depressive disorder (MDD) determined by structured psychodiagnostic clinical interview.

Psychiatric Diagnoses and Antipsychotic Medication Use Nearly 65% (n ⫽ 164) of the sample were taking some form of psychotropic medication. Table 2 details current and lifetime psychiatric diagnoses and use of antipsychotic medications. Thirty-three veterans (13%) identified use of an antipsychotic medication (risperidone, quetiapine, or olanzapine). Off-label use of antipsychotic medications was notable such that, of the 33 participants with antipsychotic medication use, only 27% met current or lifetime criteria for a diagnosis of a psychotic disorder. PTSD was the most common psychiatric diagnosis among those using an antipsychotic medication (73% with at least moderate severity), followed by alcohol (64%) and substance (61%) abuse or dependence. Antipsychotic medication use tended to be more prevalent among those with higher levels of PTSD. Thus, 60% of the veterans who used any antipsychotic medications (n ⫽ 20) had PTSD symptoms falling within the severe range (80 or more) on the CAPS. Specifically, those using antipsychotic medication had an average CAPS score of 79 (⫾20), compared with an average CAPS score of 60 554

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(⫾30) among those without antipsychotic medication use (p ⫽ 0.001). Also notable was the finding that those individuals using antipsychotic medication were significantly more likely to meet criteria for lifetime substance abuse or dependence (73%) compared with those who did not use antipsychotic medications (37%; p ⫽ 0.01). PTSD Severity, Antipsychotic Medications, and Metabolic Syndrome Status Table 4 presents the results of the logistic regression model to predict metabolic syndrome status. The overall regression model provided an adequate model fit (⫺2 log likelihood ⫽ 316.354, ␹2 ⫽ 24.027, p ⫽ 0.008). Parameter estimates provided consistent support for the overall logistic regression model reported. As with our previous investigation, being older (Wald ⫽ 3.86, p ⫽ 0.050, OR ⫽ 1.03), male gender (Wald ⫽ 4.84, p ⫽ 0.028, OR ⫽ 0.17) and higher PTSD severity as represented by the CAPS total score (Wald ⫽ 4.04, p ⫽ 0.044, OR ⫽ 1.01) were significantly and uniquely associated with higher metabolic syndrome risk. Antipsychotic medication use, however, did not appear to be a significantly unique predictor of metabolic syndrome (Wald ⫽ 0.30, p ⫽ 0.587, Psychosomatics 53:6, November-December 2012

Heppner et al.

TABLE 3.

Medical Characteristics of Veterans (n ⴝ 253) All Veterans (n ⴝ 253)

Without Antipsychotic Medications (n ⴝ 220)

With Antipsychotic Medications (n ⴝ 33)

No. (%) 101 (40)

No. (%) 85 (39)

No. (%) 16 (48)

ns

44 (17) 99 (39) 109 (43)

39 (18) 85 (39) 96 (44)

5 (15) 14 (42) 13 (39)

ns ns ns

Mean (SD) 29.3 (5.6) 189.5 ⫾ 141.8 42.7 ⫾ 11.3

Mean (SD) 29.3 (5.8) 187.1 ⫾ 122.7 42.3 ⫾ 9.7

Mean (SD) 29.0 (4.3) 189.9 ⫾ 144.7 42.8 ⫾ 11.5

ns ns ns

130.8 ⫾ 15.3 81.7 ⫾ 10.0

128.1 ⫾ 17.4 82.2 ⫾ 9.7

131.2 ⫾ 15.0 81.6 ⫾ 10.1

ns ns

0.97 ⫾ 0.07 0.85 ⫾ 0.06 106.4 ⫾ 26.8

0.97 ⫾ 0.06 0.85 ⫾ 0.05 108.5 ⫾ 27.7

0.98 ⫾ 0.07 0.85 ⫾ 0.06 106.1 ⫾ 26.7

ns ns ns

Categorical variables Metabolic syndrome (prevalence)a Body mass index groups Normal (BMI ⬍25) Overweight (BMI 25–30) Obese (BMI ⱖ 30) Continuous variables BMI Serum triglycerides HDL Blood pressure Systolic Diastolic Waist-to-hip ratio Men Women Plasma glucose concentration

Sig. (p)

BMI ⫽ body/mass ratio; HDL ⫽ high density lipoprotein; ns ⫽ no significance. a Metabolic syndrome status if 3 of 5 criteria are present (serum triglycerides ⬎150 mg/dL, high density lipoprotein ⬍35 mg/dL, blood pressure ⱖ130/85 mm/Hg, waist-to-hip ratio ⱖ0.90 for men and ⱖ0.85 for women, plasma glucose concentration ⱖ110 mg/dL).

OR ⫽ 1.25) when in context of the selected predictors (including severity of PTSD). Figure 1 depicts the distribution of antipsychotic medication use across levels of PTSD and compared by metabolic syndrome status. No significant group differences were observed with regard to the prevalence of metabolic syndrome by PTSD severity or by antipsychotic medication use.

TABLE 4.

Based on the bootstrap analysis, age was a significant predictor of metabolic syndrome status (significant in 30% of the 1000 replications), followed by lifetime nicotine abuse or dependence (21%), and history of substance use or dependence (19%) and PTSD (14%). Antipsychotic medication status was significant in 8% of the replications.

Logistic Regression Model Predicting Metabolic Syndrome Score 95% CI

Variable Sociodemographic factors Age Racea Gender Years of education Behavioral factors Nicotine abuse Substance abuse Alcohol abuse Psychiatric Factors MDD CAPSb Antipsychotic medication use

Estimate

SE.

Wald

Sig. (p)

Odds Ratio Lower

Upper

0.033 ⫺0.350 ⫺1.774 0.014

0.017 0.327 0.807 0.059

3.857 1.142 4.835 0.058

0.050 0.285 0.028 0.810

1.034 0.705 0.170 1.014

1.000 0.371 0.035 0.903

1.069 1.339 0.825 1.139

⫺0.425 0.390 ⫺0.295

0.282 0.299 0.335

2.266 1.700 0.776

0.132 0.192 0.378

0.654 1.477 0.745

0.376 0.822 0.387

1.137 2.653 1.435

⫺0.247 .011 0.227

0.297 0.005 0.417

0.691 4.040 0.296

0.406 .044 0.587

0.781 1.011 1.255

0.437 1.000 0.554

1.398 1.021 2.842

CI ⫽ confidence interval; MDD ⫽ major depressive disorder; PTSD ⫽ post traumatic stress disorder. a Statistic reflects difference in metabolic risk comparing veterans of non-white to those of white ethnicity. b Clinician-administered PTSD scale (CAPS).

Psychosomatics 53:6, November-December 2012

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FIGURE 1.

Distribution of Antipsychotic Medication Use and Metabolic Syndrome by PTSD Severity on the Clinician-Administered PTSD Scale (CAPS) (n ⴝ 253).

Without an
psycho
c medica
on With an
psycho
c medica
on

12 (27%) 1 (3%)

4 (14%) No Metabolic Syndrome

0 (0%) 0 (0%) 22 (100%) 7 (100%) 0 (0%)

17 (100%) 7 (87%) 1 (13%)

Metabolic Syndrome

0-19 CAPS Score PTSD Severity asymptoma
c

38 (97%) 25 (86%)

33 (73%)

15 (88%) 29 (85%)

27 (77%)

5 (15%)

8 (23%)

60-79 severe

80+ extreme

2 (12%)

20-39 mild

40-59 moderate

(80ⴙ) Extreme; (60 –79) Severe; (40 –59) Moderate/Threshold; (20 –39) Mild/Subthreshold; (0 –19) Asymptomatic/Few symptoms.

DISCUSSION In this sample of veterans presenting for outpatient mental health treatment, PTSD severity was significantly associated with higher risk for metabolic syndrome. Additionally, use of antipsychotic medication did not appear to confer an increased risk of metabolic syndrome above and beyond PTSD severity and the other sociodemographic, psychiatric, and behavioral factors assessed. Although only a small proportion of our sample were prescribed antipsychotic medication (13% overall), 73% of the subjects (n ⫽ 24) who were prescribed this regimen did not meet criteria for a diagnosis of psychotic disorder. Furthermore, those using antipsychotic medications had more severe levels of PTSD compared with those not using this treatment, but the usage of antipsychotic medications did not confer independent additional risk for metabolic syndrome in this study. Interestingly, in a previous study of 203 participants recruited from community, VA nursing and board and care facilities and VA psychiatric outpatient clinics who were taking antipsychotic medications, Jin and colleagues observed a higher prevalence of metabolic syndrome among patients with PTSD who also experienced psychotic symptoms (72%), com556

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pared with those diagnosed with schizophrenia (60%), mood disorder (58%), and dementia (56%), which suggests that PTSD may carry a higher risk for metabolic syndrome than other psychiatric conditions, even when those conditions are associated with a significant amount of antipsychotic drug usage.31 The two studies together provide converging evidence of the metabolic risk associated with PTSD. Jin and colleagues solely enrolled psychiatric outpatients who needed ongoing antipsychotic treatment. The present study included veterans who were presenting for enrollment in mental health services in post-deployment mental health clinics. Of this sample, only a few were prescribed antipsychotic medications, but many were diagnosed with one or more psychiatric conditions. Both studies, using slightly different samples, found PTSD to be associated with increased metabolic syndrome risk and perhaps together provide strong support for the metabolic risk associated with PTSD, independent of antipsychotic medications. Findings by Jin and colleagues suggest that even compared with non-PTSD psychiatric samples (such as schizophrenia, which has been extensively studied with regard to metabolic disturbances), those with PTSD appeared to have greater Psychosomatics 53:6, November-December 2012

Heppner et al. risk. Our study shows that metabolic syndrome risk is present even before the initiation of antipsychotic medications. Findings from both studies, taken together, may suggest that without antipsychotic medications, moderately severe PTSD confers metabolic risk and that with antipsychotic medications, having chronic PTSD confers more risk than other chronic psychiatric disorders. This is consistent with Haupt and Newcomer’s review of studies examining glucose dysregulation in major depression and schizophrenia.32 They posit that there may be underlying glucose metabolic abnormalities among these individuals that may be independent of the medications used to treat symptoms. Additionally, a complex interplay likely exists between physical disease, psychiatric symptomatology, medications, lifestyle, and individual pharmacogenetics. The present study is the first to concurrently examine severity of PTSD and the use of antipsychotic medications and how these relate to the risk for the development of metabolic syndrome. An important limitation of the present study is the lack of information about duration of PTSD symptoms. While many of the participants served in eras involving combat, we are unable to determine if the trauma precipitating the current PTSD symptoms occurred during their military services or otherwise. This would have been an important variable to analyze because considering the concept of allostatic load as applied to PTSD (where hormonal homeostatic mediators of the stress response are seen as having potentially damaging effects over the long run), it would be reasonable to posit that a longer duration of PTSD symptoms would allow for more time for underlying stressrelated dysregulation to cause irreversible changes and consequent physiological abnormalities.4,33,34 Similarly, obtaining information on duration of antipsychotic medication

treatment may also be helpful in teasing out relative contributions of PTSD severity and antipsychotic medication use on metabolic syndrome status as a longer duration of treatment would also be presumptively associated with greater physiological burden Finally, the current sample included mostly male veterans of primarily Caucasian ethnicity, so findings may not generalize to non-veteran populations. It would be important to study this association in more diverse samples (with regard to gender and ethnicity) and including PTSD resulting from non-combat trauma. CONCLUSION The health-related impacts of PTSD are widespread and significant. The risk of metabolic syndrome in a treatmentseeking veteran population appeared to be better accounted for by severity of PTSD than by antipsychotic medication use. However, a longitudinal study is strongly recommended to understand the role of PTSD severity and antipsychotic medication use over time on development of metabolic syndrome. Future research directed toward improving and disseminating treatments for PTSD needs to incorporate measures of biological burden (such as metabolic syndrome) to quantify the risks and benefits of such treatments on the physical health of those living with chronic PTSD. Disclosure: The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article. This study, data collection, and analysis have been funded by through VA Research mechanisms (VA Cooperative Study Program) and the VA Center of Excellence for Stress and Mental Health (CESAMH). The study acknowledges data collection efforts of Cincinnati VA PTSD and Gulf War Program staff and researchers.

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6. Trief PM, Ouimette P, Wade M, Shanahan P, Weinstock RS: Post-traumatic stress disorder and diabetes: comorbidity and outcomes in a male veterans sample. J Behav Med 2006; 29(5): 411– 418 7. Kubzansky LD, Koenen KC, Spiro A, III, Vokonas PS, Sparrow D: Prospective study of posttraumatic stress disorder symptoms and coronary heart disease in the normative Aging Study. Arch Gen Psychiatry 2007; 64(1):109 –116 8. Boscarino JA: A prospective study of PTSD and early-age heart disease mortality among Vietnam veterans: implications for surveillance and prevention. Psychosom Med 2008; 70(6): 668 – 676 9. Heppner PS, Crawford EF, Haji UA, Afari NM, Hauger RL, Dashevsky BA, et al: The association of posttraumatic stress

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Psychosomatics 53:6, November-December 2012