Trauma history and risk of irritable bowel syndrome in womenveterans

D. L. White1,2,3, L. S. Savas1,3,4,5, K. Daci2, R. Elserag6, D. P. Graham1,7,8, S. J. Fitzgerald1,3,S. L. Smith6, G. Tan9, and H. B. El-Serag1,2,3

1 Section of Health Services Research, Department of Medicine, Baylor College of Medicine,Houston, Texas2 Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College ofMedicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas3 Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research andDevelopment Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center,Houston, Texas4 Section of Community and Family Medicine, Department of Medicine, Baylor College ofMedicine, Houston, Texas5 University of Texas-Houston School of Public Health, Division of Health Promotion andBehavioral Sciences, Center for Health Promotion and Prevention Research, Houston, Texas6 Women Veterans Program, Michael E. DeBakey Veterans Affairs Medical Center, Houston,Texas7 The Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine,Houston, Texas8 Veterans Affairs South Central Mental Illness Research, Education, & Clinical Center(MIRECC), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas9 Department of Anesthesiology, Baylor College of Medicine and Michael E. DeBakey VeteransAffairs Medical Center, Houston, Texas

AbstractBackground—Over 1.8 million women in the U.S. are veterans of the armed services. They areat increased risk of occupational traumas, including military sexual trauma. We evaluated theassociation between major traumas and irritable bowel syndrome among women veteransaccessing VA healthcare.

Methods—We administered questionnaires to assess trauma history as well as IBS, PTSD anddepression symptoms to 337 women veterans seen for primary care at VA Women’s Clinic

Corresponding author: Hashem B. El-Serag, MD, MPH, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Blvd.(MS 152), Houston, Texas 77030, hasheme@bcm.edu.Authors’ Involvement: Donna White: Conception, analysis, writing, approval of final manuscriptLara Savas: Conception, approval of final manuscriptKuang Daci: Conception, approval of final manuscriptRola Elsearg: Conception, approval of final manuscriptDavid P. Graham: Conception, approval of final manuscriptStephanie Fitzgerald: Conception, approval of final manuscriptShirley Laday Smith: Conception, approval of final manuscriptGabriel Tan: Conception, approval of final manuscriptHashem El-Serag: Conception, writing, approval of final manuscript

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Published in final edited form as:Aliment Pharmacol Ther. 2010 August ; 32(4): 551–561. doi:10.1111/j.1365-2036.2010.04387.x.

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between 2006 and 2007. Logistic regression was used to evaluate the association betweenindividual traumas and IBS risk after adjustment for age, ethnicity, PTSD and depression.

Results—IBS prevalence was 33.5%. The most frequently reported trauma was sexual assault(38.9%). Seventeen of eighteen traumas were associated with increased IBS risk after adjusting forage, ethnicity, PTSD and depression, with six statistically significant (range of adjusted oddsratios (OR) between 1.85 [95% CI, 1.08–3.16] and 2.6 [95% CI, 1.28–3.67]). Depression andPTSD were significantly more common in IBS cases than controls, but neither substantiallyexplained the association between trauma and increased IBS risk.

Conclusions—Women veterans report high frequency of physical and sexual traumas. Lifetimehistory of a broad range of traumas is independently associated with an elevated IBS risk.

KeywordsIrritable bowel syndrome; veterans; women; PTSD; trauma; Department of Veterans Affairs;depression

BackgroundIrritable bowel syndrome (IBS) is a prevalent and costly functional gastrointestinal disorder.An IBS diagnosis is based upon presence of chronic or recurrent bowel abnormalities withabdominal pain relieved by defecation and not explainable by other causes. IBS is the mostfrequent cause for gastroenterologist visits in the U.S.(1) responsible for 3.7 millionphysician visits annually(2) and direct medical costs in excess of 1.6 billion dollars.(3)Considerable indirect costs, in excess of $19 billion dollars annually(3), also result fromsubstantially higher total healthcare utilization and costs(4–6) and reduced workproductivity.(5–7) Furthermore, a markedly decreased health-related quality of life isconsistently reported in patients with IBS (4–6,8–10), with an estimated 75% of cases stillsymptomatic after ten years.(11)

Although IBS is known to be clinically under-recognized among both genders in the generalpopulation(12), IBS prevalence in clinical settings is 2–3 times greater in women.(13) Thisfemale preponderance has been attributed to a combination of sex-based physiologicaldifferences and gender-based psychosocial and environmental differences, includinglikelihood of experiencing sexual trauma.(14) Several biological factors have beenassociated with IBS risk including GI infection(15–17), food intolerance/allergies(18,19),and genetic susceptibility.(20–23) Psychological disorders including depression(24–27),anxiety(24,27–29), and post-traumatic stress disorder (PTSD)(30–33) are more common inIBS cases.

The over 1.8 million women veterans in the U.S.(34) constitute a large occupational cohortat risk of IBS. Women also comprise approximately 14% of all active duty militarypersonnel and 20% of all new military recruits. Currently, around 11% of all active-dutyservice members serving in Iraq and Afghanistan (OIF/OEF) conflicts are women, withwomen veterans of OIF/OEF now the single largest living group of women veterans(~187,000).(34–36) Women veterans are known to have increased risk of occupationaltrauma including in association with deployment and combat.(37) They also have high ratesof lifetime sexual traumas including rape during military service.(38–40)

We previously reported a high survey-based prevalence of IBS as well as of psychologicaldistress, including depression and post-traumatic stress disorder (PTSD), in a sample ofwomen veterans receiving primary care at a Department of Veterans Affairs (VA) medicalcenter.(32) The primary aims of our current research were: 1) to determine survey-based

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prevalence of a broad range of individual traumas in a larger sample of women veterans, and2) to evaluate the association between individual traumas and IBS risk after adjustment forPTSD and depression. An associated exploratory aim was to perform a medical recordreview to assess clinical recognition of IBS in women veterans who access VA healthcare.

MethodsSample and Questionnaires

We recruited consecutive women veterans aged 18–70 years old at the time of a scheduledprimary medical care appointment in the Women’s Clinic at the Michael E. DeBakey VAMedical Center in Houston, Texas. All eligible women veterans were approached aboutstudy participation by a female researcher who was not part of the clinical staff. Studyparticipants completed a self-administered survey prior to their clinical visit and receivedfive-dollar remuneration. Our research protocol was approved by the Baylor College ofMedicine Institutional Review Board.

We used the validated Bowel Disorder Questionnaire (BDQ)(41,42) to measure type,frequency and severity of gastrointestinal symptoms experienced during the previous year.We applied symptom-based diagnostic criteria adapted from gold-standard Rome II clinicalguidelines to define if a woman veteran had IBS.(32)

We used the Mississippi Scale for Combat-Related PTSD (M-PTSD) to define presence ofPTSD using the recommended diagnostic cutoff of ≥107, a level at which the M-PTSDdemonstrated a 93% sensitivity in comparison to the gold-standard clinical diagnosis.(43)Depression was assessed using the validated Beck Depression Inventory, second edition(BDI-II).(44) We categorized total instrument sum score using recommended cut-points of0–13 (no-minimal depression), 14–19 (mild depression), 20–28 (moderate depression) and29–63 (severe depression).

We determined whether a woman veteran ever experienced a broad range of major lifetraumas using the validated 18-item Trauma History Questionnaire (THQ)(45). Our interimanalyses suggested a very high prevalence of sexual traumas among our women veteranstudy participants. These results in conjunction with greatly increased national media andpublic awareness about the scope and burden of military sexual trauma(46) led to ouraddition of a second trauma measure, the Trauma Questionnaire (TQ)(47), to specificallycapture timing of abusive traumas (i.e., sexual assault/rape, sexual harassment, and domesticviolence) in relation to military service. The TQ was given to the final 25% of our studyparticipants.

Electronic Medical Record ReviewWe evaluated VA electronic medical record of all BDQ-identified IBS cases for presence ofalternate explanations for their symptoms. We also evaluated medical records for allparticipants for presence of a clinical IBS diagnosis and/or at least 2 cardinal symptomsconsistent with a possible IBS diagnosis during the one-year time period prior to surveyadministration. Finally, we reviewed the records of a random sample of women veteranswho refused to participate to see if they differed in likelihood of having IBS diagnosis orsymptoms compared to study participants.

Statistical AnalysesWe compared sociodemographic characteristics and IBS risk factors between womenveterans with IBS (cases) and those without IBS (controls) using the χ2 test for categoricalvariables and Student’s T-test for continuous variables. We evaluated how specific traumas

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influence IBS risk using logistic regression. We performed three sets of multivariateanalyses. In the first minimal multivariate analysis, we adjusted for two well-establishedconfounders, age and ethnicity. In the second intermediate analysis, we also adjusted forPTSD to see if any observed association between a specific trauma and IBS risk wasattributable to its presence. In the third or full multivariate model, we additionally adjustedfor presence of depression. We evaluated potential effect modification by creating all first-level interaction terms and assessing their significance using the Wald test. Interaction termswere included in reported models if significant at p<0.15. All logistic regression results arereported as odds ratios with associated 95% confidence intervals (CI).

Trauma timing in relation to military service—We calculated lifetime prevalence ofabusive traumas in the final 83 women veterans who had been given the TQ. Participantswere classified as having never experienced the trauma, experienced the trauma duringmilitary service, or experienced the trauma only outside of military service. To evaluateutility of the THQ and TQ to identify forcible sexual assault or rape, we calculatedconcordance between their most directly comparable questions using the kappa statistic.

Validation analyses of key study measures and clinical recognition of IBS—Toassess our use of the BDQ to identify cases, we first calculated the false-positive rate as theproportion of BDQ-identified IBS cases with exclusionary medical conditions or symptomsin their medical records. We also calculated negative and positive predictive values (NPVand PPV respectively) or probability that the BDQ-derived IBS case-status accuratelypredicts IBS case-status in the medical record. Using the validated BDQ and adapted RomeII clinical guidelines as the ‘gold standard’, we calculated clinical under-recognition of IBSas the proportion of BDQ-identified IBS cases without a confirmed, suspected or differentialdiagnosis of IBS in their medical record. Finally, to assess potential selection bias, we usedthe χ2 test to compare the proportion of participants with either a clinical IBS diagnosis or ≥2 symptoms suggestive of IBS reported in the medical record in both our entire cohort andin a random sample of non-participants.

All analyses were conducted using SPSS version 16.0 (SPSS Inc., Chicago, IL).

ResultsDemographic and clinical features

We recruited 337 consecutive women veterans prior to their primary care visit at theWomen’s Clinic at the Michael E. DeBakey VA Medical Center in Houston, Texas(11/2005–2/2006, 3/2007–6/2007). Over 95% of eligible women veterans approached aboutthe study participated. The mean age of participants was 48.5 years, and most were African-American (48.1%) or non-Hispanic White (39.7%). (Table 1)

Approximately 33.5% (n=113) were BDQ-defined as IBS cases, with IBS prevalence amongWhites modestly higher than among African-Americans (38.8% vs. 34.0% respectively,N.S.). IBS cases were slightly younger than IBS-free controls (mean age 46.9 vs. 49.3 years,P=0.06). Although the proportion of African–Americans was similar among IBS cases andcontrols (48.7% vs. 47.8% respectively, N.S.), cases were significantly more likely to beWhite (46.0% vs. 36.6%) and much less likely to be Hispanic (5.3% vs. 15.2) than controls.IBS cases were significantly more likely to have PTSD (22.1% vs. 10.7%, P=0.006) ordepression (44.2% vs. 29.5%, P=0.01) than IBS-free controls. (Table 1) As (98%) of IBScases had diarrhea as a contributing or primary clinical feature (data not shown), allsubsequent multivariate analyses apply to the entire sample without adjustment for clinicalfeatures.

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Trauma history as predictor of IBSThe most frequently reported traumas on the THQ were “ever being forced to have sexagainst your will” (46.6%) and “being fondled under force or threat” (41.8%). (Table 2)Both were more common in IBS cases than controls.

Collectively, nine traumas in univariate analysis were significantly associated with IBS(ORs=1.79–2.24). (Table 3) Another four traumas were associated with increased riskclosely approaching significance (ORs=1.56–1.74, 0.05≤ P ≤0.06).

In the first minimal multivariate model which adjusted for age and ethnicity, eleven traumas(61%) were associated with significantly increased risk (ORs=1.72 – 2.43), with anotherfour (22%) closely approaching significance. (Table 3) In the second model which alsoadjusted for PTSD, the excess IBS risk associated with individual traumas was slightlyattenuated in comparison to the minimal model, with seven traumas (39%) still associatedwith significant excess risk (ORs=1.84 – 2.19). Similar to results from the first or minimalmodel, all but one remaining trauma, although non-significant, were associated with excessrisk (ORs=1.27–1.71). (Table 3) Across all trauma histories, PTSD was consistentlyassociated with an independent 100% increase in IBS risk (ORs =2.02–2.70, data notshown). In the final multivariate model that also adjusted for depression, IBS risk was againattenuated only slightly, significant excess risk was still observed for six traumas, withanother four closely approaching significance. Further, additional adjustment for depressiononly minimally attenuated the independent excess IBS risk associated with PTSD for all butthree traumas (home break-in, seeing/handling dead bodies not related to funerals, andserious illness), where there was evidence of strong confounding by depression. (data notshown)

Only one trauma, “having someone close to you killed by a drunk driver”, was notassociated with increased IBS risk in univariate or multivariate analysis.

We found no evidence of interaction between any main effects or of lack of model fit in anymultivariate model.

Military sexual trauma (MST) and overlap with other abusive traumasThe final 83 study participants completed the TQ. There was high concordance (κ=0.75,P=0.001) between comparable TQ and THQ items for occurrence of forcible sexual assaultexpressed as ‘Has anyone ever used force or threat of force to have sex with you againstyour will?’ (TQ) and ‘Has anyone ever made you have intercourse, oral or anal sex againstyour will?’ (THQ) Specifically, 90% of women who reported experiencing sexual assault onthe TQ also reported experiencing it on the THQ.

Approximately 60% of women who completed the TQ reported experiencing ≥1 sexualassault during their lifetime, with 21% reporting forcible sexual assault during militaryservice. (Figure 1) Slightly more than one-third (34%) reported sexual abuse duringchildhood, with 25% subsequently reporting sexual assault or rape during military service.More women veterans reported domestic violence than sexual harassment or assaultoccurred during military service (49% vs. 38% vs. 21% respectively). Overall, almost two-thirds experienced ≥1 of these three abusive traumas (rape, sexual harassment and domesticviolence) during military service, with 39% of abused women experiencing ≥2 traumas.(data not shown)

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Validation of BDQ to identify IBS cases and evaluation of selection biasUse of the BDQ to identify IBS cases was associated with a low false positive rate, as <4%had exclusionary conditions anywhere in their medical record. Use of the BDQ to identifypresence of an IBS diagnosis in the medical record was associated with good NPV (0.73,[95% CI, 0.67–0.78]). However, the corresponding PPV was lower (0.65, [95% CI, 0.51–0.77]).

Overall, medical-record documented prevalence of either an IBS diagnosis or of ≥2symptoms suggestive of IBS in the year prior to the index clinic visit were similar in studyparticipants and in a random sample of 35 non-participants (14.3% vs. 16.8% for diagnosisand 17.1% vs. 17.1% for ≥2 symptoms, both N.S.).

DiscussionTo our knowledge, the current study conducted in 337 women veterans receiving primarymedical care at the VA is the first study to assess lifetime history of a broad range ofmultiple individual traumas as risk factors for symptom-confirmed IBS in any veteran ormilitary population.

All but one of the broad range of traumas examined were associated with increased IBS riskin women veterans, most with modest to moderate 50–115% excess risk. The excess riskassociated with individual traumas persisted with only minor attenuation in multivariateanalyses even after adjusting for other well-established risk factors, specifically age,ethnicity, depression and PTSD. However, the number of traumas reaching or approachingsignificance was reduced given concomitant reduction in study power.

The very high prevalence of sexual traumas observed in this study is not completelysurprising. A mandated VA-wide clinical screening for military sexual trauma demonstrateda 22% prevalence rate in women veterans.(38) To better understand how often a self-reported history of sexual assault may have in fact included forcible sexual assault duringmilitary service, the final 25% of participants completed a second trauma measure, theTrauma Questionnaire (TQ).(47) More than 40% of women reporting a history of non-childhood sexual assault on this measure reported experiencing forcible sexual assaultduring military service. However, the substantive reduction in sample size, particularly ofIBS cases, precluded valid assessment of abusive traumas experienced specifically duringmilitary service as independent IBS risk factors.

Depression and PTSD are among the top three diagnostic codes assigned to women veteransusing the VA, with both shown to increase IBS risk in women veterans.(31,32) PTSD wasassociated with an independent 100% increased IBS risk for 15 of 18 traumas we assessed.However, PTSD neither substantially explained nor modified the independent increased IBSrisk conveyed by individual traumas. This modest to moderate increased IBS risk persistedfor most traumas even after additional adjustment for depression.

A number of studies have evaluated individual abusive traumas like sexual abuse as IBS riskfactors,(48–57) with most reporting increased IBS risk.(49–54,56,57) One group evaluatedabusive traumas as IBS risk factors in a manner generally comparable to ours, i.e., a survey-based epidemiologic study conducted in a single general adult population not selected basedon disease or clinical sub-specialty and with adjustment for concomitant psychologicalcomorbidity. Their initial study was a mail survey to residents of a Penrith, Australia(48),with subsequent interview of a small sample of initial participants.(55) In contrast to ourfindings, they found almost no abusive traumas were associated with excess IBS risk afteradjustment for general overall psychological morbidity level and neuroticism. Some of this

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discrepancy between our study findings is likely attributable to substantial differences in ourunderlying target populations, including our restriction to women, and specifically womenveterans, who have a high lifetime trauma burden, and in measures of psychologicalcomorbidity. Other relevant factors may include our use of direct recruitment with highparticipation rate compared to their use of a mailed survey and follow-up interviews in asub-sample of participants with lower participation rates. The consistency of our findingssuggestive of excess IBS risk with many abusive as well as non-abusive traumas supportsthe internal validity of our findings. Future comparably conducted research may help clarifywhether abusive as well as non-abusive traumas are independently associated with excessIBS risk after adjusting for similar psychological comorbidities in other civilian and militarypopulations.

Most studies that have evaluated the association between military service and risk of GIsymptoms or disorders including IBS examined deployment in veterans of the first GulfWar. A 2010 Institute of Medicine (IOM) report evaluating this literature highlighted severalkey individual study findings including: 1) epidemiologic data demonstrating substantialdeployment-related increases in IBS; 2) physiologic data demonstrating persistent low-gradecolonic inflammation and increased visceral hypersentivity among deployed Gulf Warveterans with IBS or IBS-type symptoms; and 3) epidemiologic data demonstrating greatlyincreased risk of IBS among veterans with a history of gastroenteritis, with effectsparticularly elevated among deployed veterans.(58) Unfortunately, we could not assess ifthere was a deployment-IBS association in our women veterans because we did not haveaccess to necessary Department of Defense data to confirm deployment, including a historyof combat or deployment-related gastroenteritis. However, our finding that multipleindividual traumas, including many that may plausibly happen during deployment,independently increased risk of symptom-confirmed IBS in women veterans is consistentwith the IOM findings. Our study offers several additions to the IOM-cited literature. First,we demonstrated that a trauma-IBS association exists for a broad range of traumas andpersists even after adjustment for PTSD and depression. These two key psychologicalcomorbidities in veterans that often co-occur with IBS were not controlled for in most ofthese Gulf War studies which often evaluated IBS as only one of multiple potential healthoutcomes. Second, because our study participants spanned a broad age-range, our resultssuggest a trauma-IBS association is unlikely to be limited to a single military cohort or era.Finally, our findings demonstrate a trauma-IBS association exists in women veterans, apopulation that was either absent or represented only a very small minority of the veteransevaluated in these earlier Gulf War studies.

Recent experimental and clinical studies have evaluated the association between early lifetrauma and stress in relation to IBS. In the neonatal maternal separation model (NMS) ofIBS in rodents, several traumatic exposures during the early neonatal period increasevisceral hyperalgesia,(59–62) a hallmark IBS symptom. For example, recent NMS studiesdemonstrated receipt of noxious stimuli like colorectal distention in this hyporesponsiveperiods leads to alterations in nociception, including increased immune and neurochemicalresponsivity at the level of the enteric nervous system.(61,63) Others have shown this NMS-related visceral hyperalgesia persist in adulthood in response to subsequent noxious stimuli.(60,62) Additional indirect evidence comes from epidemiologic studies demonstratingperinatal gastric suction(64) or living in a wartime environment during specific intervals ininfancy(65) increases risk of functional gastrointestinal disorders including IBS inadulthood.

NMS in rodents also leads to chronic dysregulation in the limbic-pituatary-hypothalamic-adrenal (LPHA) axis,(66–68) with chronic LPHA dysregulation in humans associated withPTSD and depression(69), conditions often co-occurring with IBS. A recent structural MRI

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imaging study found increased hypothalamic gray matter and thinning of the anteriormidcingulate limbic cortex in IBS cases compared to matched healthy controls.(70)Selective neural thinning that was observed only in IBS cases occurred in the supraspinaldorsolateral prefrontal cortex, which is extensively interconnected with both the limbicsystem and neocortex association areas and plays an important role in motor regulation andexecutive function. A recent functional MRI imaging study evaluated neural activation andpain perception in response to rectal distention in women, half of whom had IBS and half ofwhom had a history of abuse.(71) It demonstrated that both pain perception and a history ofabuse were independently associated with increased activity in posterior and middle dorsalcingulate limbic cortex, with greatest effects observed in women who had both IBS and ahistory of abuse. Decreased activity in another limbic structure, the supragenual anteriorcingulate cortex, was only observed in women with IBS who also had an abuse history.However, given the cross-sectional design and limited sample size of these studies, it iscurrently unknown to what extent these structural and functional differences may reflectincreased susceptibility to versus are a result of or are reinforced by clinical presence of IBS.

Our results that a broad range of traumas are associated with increased IBS risk in womenveterans are consistent with this emerging data suggesting potential biological linkagebetween trauma and IBS within the complex reciprocal interplay of the gut and the entericnervous, central nervous and neuroendocrine systems. Our results also suggest the period inwhich traumas influence IBS risk may extend beyond early childhood into adulthood andalso include a much broader range of major traumas than just abusive traumas. Additionalindirect evidence supportive of potential role for trauma and stressors experienced inadulthood to increase IBS susceptibility comes from a recent experimental study in younghealthy adult women that demonstrated visceral hypersensitivity and maladaptive intestinalepithelial responsitivity, both well-known to occur with IBS, were increased after receipt ofnoxious jejunal stimulation, with effects larger in healthy women placed under conditions ofmoderate compared to low background stress.(72)

Our study has multiple strengths including the prospective recruitment of a large andmultiethnic sample of women veterans, restriction to a general care as opposed to specialty-or disease-specific clinical setting, high participation rate and use of validated measures. Wealso verified all IBS cases and controls in our study were veterans since up to half of womenaccessing VA healthcare are non-veterans (e.g., spouses/dependents or employees).(73) Ourphysician-performed medical record review substantiated our measure for the presence ofIBS. It also provided data suggestive of substantial under-recognition of IBS among womenveterans using the VA. Finally, to our knowledge, our study is the most comprehensiveevaluation of individual traumas including multiple major lifetime traumas not previouslyexamined for IBS in any population.

Our study also has several limitations. First, our study evaluated women veterans who havevery high prevalence of IBS symptoms, trauma and psychological disorders; therefore, ourfindings may not generalize to women veterans who do not use the VA, to civilian women,or male veterans. The cross-sectional design precludes causal inferences as we cannotreliably establish whether IBS began before or after a trauma occurred. However, theconsistent finding that a broad range of traumas, both abusive and non-abusive, experiencedover a lifetime increased IBS risk suggests trauma is likely antecedent to IBS in at leastsome cases. Lastly, although recent community data suggests most IBS cases aresymptomatic a decade later,(11) we were unable to evaluate differences in trauma-IBSassociation between those with long-standing versus only recent IBS.

Our study demonstrated lifetime history of a broad range of major life traumas beyond thoseexperienced in early childhood or that are abusive in nature are associated with increased

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IBS risk in women veterans, even after adjusting for their most common psychologicalcomorbidities, depression and PTSD. Our findings also have potentially importantimplications for healthcare delivery for women veterans. Specifically, they suggest womenveterans who use the VA and who screen positive for PTSD, depression or military sexualtrauma during system-mandated universal screenings for these conditions may also benefitfrom additional screening for IBS. Finally, our results suggestive of considerableunderdiagnosis of IBS in women veterans, also suggest that obtaining a detailed traumahistory may be useful in facilitating appropriate clinical recognition and diagnosis of IBS.

AcknowledgmentsThis material is based upon work supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020)and a project grant from Novartis pharmaceuticals (PI: H.B. El-Serag, MD, MPH). Dr. White receives salarysupport from a Career Development Award (NIDDK K-01, DK081736-01), Dr. Savas from a National ResearchService Award (5 T32 HP10031-09) and the Health Cancer Education and Career Development Program (NCI/NIHR25-CA-57712), and Dr. El-Serag from an Advanced Career Development Award (NIDDK K-24, DK078154-03).

Role of the Funding Source: The study was funded in part by the Novartis Pharmaceuticals Corporation, the U.S.Department of Veterans Affairs and the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK).The sponsors had no role in study design, implementation, analysis, interpretation or decision to publish.

Abbreviations

BDI-II Beck Depression Inventory, 2nd edition

BDQ Bowel Disorder Questionnaire

CI confidence interval

IBS irritable bowel syndrome

M-PTSD Mississippi Scale Combat-Related PTSD

MST military sexual trauma

PTSD post-traumatic stress disorder

THQ Trauma History Questionnaire

TQ Trauma Questionnaire

VA Department of Veteran Affairs

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Fig 1.History of Sexually Abusive Traumas reported on Trauma Questionnaire (TQ) by final 83women veteran study participants*.*Only 1 missing value (1%)^Sexual abuse in childhood by age 13 and perpetrated by someone at least 5 years older.^^TQ-defined sexual assault or sex against will by force or threat of force occuring at leastonce during military service.^^^Any non-childhood sexual assault that occurred at any time other than during militaryservice.^^^^Given TQ question structure, can only determine if MSA or another non-MSA occuredbut not if both an MSA and a non-MSA occurred.

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Tabl

e 1

Soci

odem

ogra

phic

cha

ract

eris

tics o

f 337

wom

en v

eter

ans r

ecei

ving

prim

ary

med

ical

car

e at

a V

A W

omen

’s C

linic

stra

tifie

d ac

cord

ing

to p

rese

nce

ofirr

itabl

e bo

wel

synd

rom

e (I

BS)

1 . IBS+

IBS−

IBS+

vs.

IBS−

2

N=1

13 (3

3.5%

)N

=224

(66.

5%)

p-va

lue

Soci

odem

ogra

phic

Cha

ract

eris

tic

Age

in y

ears

Mea

n (S

D)

46.9

(10.

0)49

.3 (1

2.9)

0.06

Age

-gro

up in

yea

rs n

(%)

0.02

*

18

–30

5 (4

.4%

)21

(9.4

%)

31

–45

48 (4

2.5%

)61

(27.

2%)

46

–60

51 (4

5.1%

)11

2 (5

0.0%

)

61

+9

(8.0

%)

30 (1

3.4%

)

Eth

nici

ty n

(%)

0.02

*+

A

fric

an-A

mer

ican

55 (4

8.7%

)10

7 (4

7.8%

)

W

hite

52 (4

6.0%

)82

(36.

6%)

H

ispa

nic/

Oth

er6

(5.3

%)

34 (1

5.2%

)

M

issi

ng-

1 (0

.4%

)

Edu

catio

n n

(%)

0.07

H

igh

scho

ol g

radu

ate

or le

ss9

(8.0

%)

38 (1

7.0%

)

So

me

colle

ge70

(61.

9%)

122

(54.

5%)

C

olle

ge g

radu

ate

33 (2

9.2%

)61

(27.

2%)

M

issi

ng1

(0.9

%)

3 (1

.3%

)

Mar

ital S

tatu

s n (%

)0.

61

C

urre

ntly

Mar

ried

35 (3

1.0%

)58

(25.

9%)

Pr

evio

usly

Mar

ried

59 (5

2.2%

)12

2 (5

4.5%

)

N

ever

Mar

ried

19 (1

6.8%

)43

(19.

2%)

M

issi

ng-

1 (0

.4%

)

IBS,

irrit

able

bow

el sy

ndro

me;

SD

, sta

ndar

d de

viat

ion

* Stat

istic

ally

sign

ifica

nt a

t p<0

.05.

1 Pres

ence

or a

bsen

ce o

f IB

S de

term

ined

from

resp

onse

s to

the

valid

ated

Bow

el D

isor

der Q

uest

ionn

aire

(BD

Q) c

onsi

sten

t with

a d

iagn

osis

of I

BS

usin

g ad

apte

d R

ome

II c

riter

ia. (

see

also

Met

hods

sect

ion)

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White et al. Page 162 M

issi

ng n

ot in

clud

ed in

cal

cula

tion

of te

st st

atis

tic a

s les

s tha

n 1.

5% o

f eith

er IB

S+ c

ases

or I

BS−

con

trols

had

mis

sing

val

ues.

+A

lthou

gh o

vera

ll et

hnic

dis

tribu

tions

sign

ifica

ntly

diff

eren

t, %

Afr

ican

-Am

eric

ans n

ot si

gnifi

cant

ly d

iffer

ent i

n IB

S+ a

nd IB

S− (4

8.7%

vs.

47.8

% re

spec

tivel

y).

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Tabl

e 2

Prev

alen

ce o

f sel

ecte

d tra

umas

1 , po

st-tr

aum

atic

stre

ss d

isor

der (

PTSD

)2 and

dep

ress

ion3 a

mon

g 33

7 w

omen

vet

eran

s see

n fo

r prim

ary

care

at a

VA

Wom

en’s

Clin

icac

cord

ing

to p

rese

nce

of ir

ritab

le b

owel

synd

rom

e (I

BS)

4 .

IBS+

IBS−

IBS+

vs.

IBS−

N=1

13N

=224

n (%

)p-

valu

e

Posi

tive

hist

ory

of sp

ecifi

c tr

aum

a1,5

Som

eone

trie

d to

take

thin

gs fr

om y

ou b

y fo

rce/

thre

at44

(38.

9%)

49 (2

1.9%

)0.

001*

*

Som

eone

trie

d an

d/or

succ

eede

d br

eaki

ng in

to h

ome

whi

le th

ere

21 (1

8.6%

)27

(12.

1%)

0.12

0

Serio

us a

ccid

ent a

nyw

here

49 (4

3.4%

)81

(36.

2%)

0.24

5

‘Man

-mad

e’ d

isas

ter l

ike

train

cra

sh, f

ire, e

tc. w

here

felt

you/

love

d on

es w

ere

in p

hysi

cal d

ange

r26

(23.

0%)

29 (1

2.9%

)0.

022*

Oth

er si

tuat

ion

whe

re y

ou w

ere

serio

usly

inju

red

27 (2

3.9%

)34

(15.

2%)

0.05

4^

Oth

er si

tuat

ion

fear

ed m

ight

be

kille

d/se

rious

ly in

jure

d52

(46.

0%)

72 (3

2.1%

)0.

014*

Seen

som

eone

serio

usly

inju

red/

kille

d46

(40.

7%)

72 (3

2.1%

)0.

148

Seen

or h

ad to

han

dle

dead

bod

ies (

not f

uner

als)

54 (4

7.9%

)82

(36.

6%)

0.05

8^

Clo

se fa

mily

/frie

nd k

illed

by

drun

k dr

iver

19 (1

6.8%

)38

(17.

0%)

0.94

3

Spou

se/p

artn

er/c

hild

die

d41

(36.

3%)

62 (2

7.7%

)0.

122

Serio

us o

r life

-thre

aten

ing

illne

ss32

(28.

3%)

40 (1

7.9%

)0.

033*

Forc

ed to

hav

e se

x ag

ains

t will

63 (5

5.8%

)94

(42.

0%)

0.01

9*

Fond

led

unde

r for

ce o

r thr

eat

56 (4

9.6%

)85

(37.

9%)

0.05

4^

Oth

er si

tuat

ion

with

atte

mpt

ed fo

rce

for u

nwan

ted

sexu

al c

onta

ct41

(36.

3%)

47 (2

1.0%

)0.

003*

*

Atta

cked

with

wea

pon

36 (3

1.9%

)39

(17.

4%)

0.00

3**

Atta

cked

with

out w

eapo

n an

d se

rious

ly in

jure

d29

(25.

7%)

34 (1

5.2%

)0.

023*

Any

fam

ily m

embe

r eve

r bea

ten/

push

ed h

ard

enou

gh to

cau

se in

jury

38 (3

3.6%

)45

(20.

1%)

0.00

7**

Expe

rienc

ed a

ny o

ther

ext

raor

dina

rily

stre

ssfu

l eve

nt37

(32.

7%)

51 (2

2.8%

)0.

057^

PTSD

2 ,5

Pres

ent

25 (2

2.1%

)24

(10.

7%)

0.00

6**

Dep

ress

ion3

,5

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IBS+

IBS−

IBS+

vs.

IBS−

N=1

13N

=224

n (%

)p-

valu

e

Pres

ent

50 (4

4.2%

)66

(29.

5%)

0.01

0*

* Stat

istic

ally

sign

ifica

nt a

t p<0

.05.

**St

atis

tical

ly si

gnifi

cant

at p

<0.0

1.

^ App

roac

h si

gnifi

canc

e (0

.05≤

P≤0.

06).

1 Pres

ence

of t

raum

a de

term

ined

by

self-

repo

rted

resp

onse

s to

the

valid

ated

Tra

uma

His

tory

Que

stio

nnai

re (T

HQ

).

2 Pres

ence

of P

TSD

det

erm

ined

by

self-

repo

rted

resp

onse

s to

the

valid

ated

Mis

siss

ippi

Sca

le fo

r Com

bat-R

elat

ed T

raum

a (M

-PTS

D) w

ith sc

ore ≥

107

cons

iste

nt w

ith P

TSD

dia

gnos

is.

3 Pres

ence

of d

epre

ssio

n of

at l

east

mod

erat

e le

vel d

eter

min

ed b

y se

lf-re

porte

d re

spon

ses t

o th

e va

lidat

ed B

eck

Dep

ress

ion

Inve

ntor

y-II

(BD

I-II

)

4 Pres

ence

or a

bsen

ce o

f IB

S as

det

erm

ined

by

self-

repo

rted

resp

onse

s to

the

valid

ated

Bow

el D

isor

der Q

uest

ionn

aire

(BD

Q) c

onsi

sten

t with

a d

iagn

osis

of I

BS

per a

dapt

ed R

ome

II c

riter

ia. (

see

also

Met

hods

sect

ion)

5 Less

than

3%

mis

sing

val

ues

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White et al. Page 19

Tabl

e 3

Logi

stic

regr

essi

on m

odel

s eva

luat

ing

lifet

ime

hist

ory

of in

divi

dual

trau

mas

as p

oten

tial r

isk

fact

ors f

or IB

S1 am

ong

337

wom

en v

eter

ans r

ecei

ving

prim

ary

med

ical

car

e at

a V

A W

omen

’s C

linic

.

Typ

e of

trau

ma2

Una

djus

ted

Est

imat

esA

ge- a

nd E

thni

city

-Adj

uste

dE

stim

ates

Age

-, E

thni

city

-, an

d PT

SD3 -

Adj

uste

d E

stim

ates

Age

-, E

thni

city

-, PT

SD3 -

, and

Dep

ress

ion4

-Adj

uste

d E

stim

ates

His

tory

of t

raum

a+H

isto

ry o

f tra

uma+

His

tory

of t

raum

a+H

isto

ry o

f tra

uma+

Odd

s rat

io (9

5% C

I)O

dds r

atio

(95%

CI)

Odd

s rat

io (9

5% C

I)O

dds r

atio

(95%

CI)

Som

eone

trie

d to

take

thin

gs fr

om y

ou b

yfo

rce/

thre

at2.

24 (9

5% C

I 1.3

6–3.

68)*

*2.

38 (9

5% C

I 1.4

2–3.

98)*

2.18

(95%

CI 1

.29–

3.69

)*2.

16 (9

5% C

I 1.2

8–3.

67)*

Som

eone

trie

d an

d/or

succ

eede

d br

eaki

ng in

toho

me

whi

le th

ere

1.63

(95%

CI 0

.88–

3.05

)1.

83 (9

5% C

I 0.9

6–3.

49)

1.71

(95%

CI 0

.89–

3.31

)1.

71 (9

5% C

I 0.8

8–3.

30)

Serio

us a

ccid

ent a

nyw

here

1.32

(95%

CI 0

.83–

2.10

)1.

38 (9

5% C

I 0.8

5–2.

23)

1.27

(95%

CI 0

.78–

2.08

)1.

21 (9

5% C

I 0.7

5–2.

04)

‘Man

-mad

e’ d

isas

ter l

ike

train

cra

sh, f

ire, e

tc.

whe

re fe

lt th

at y

ou/lo

ved

ones

in p

hysi

cal

dang

er

1.97

(95%

CI 1

.10–

3.56

)*2.

19 (9

5% C

I 1.1

9–4.

02)*

2.05

(95%

CI 1

.10–

3.80

)*2.

06 (9

5% C

I 1.1

1–3.

82)*

Oth

er si

tuat

ion

whe

re y

ou w

ere

serio

usly

inju

red

1.74

(95%

CI 0

.99–

3.07

)^1.

76 (9

5% C

I 0.9

9–3.

16)^

1.51

(95%

CI 0

.83–

2.77

)1.

48 (9

5% C

I 0.8

8–2.

72)

Oth

er si

tuat

ion

fear

ed m

ight

be

kille

d/se

rious

lyin

jure

d1.

79 (9

5% C

I 1.1

2–2.

87)*

1.83

(95%

CI 1

.13–

2.98

)*1.

55 (9

5% C

I 0.9

3–2.

58)

1.52

(95%

CI 0

.91–

2.55

)

Seen

som

eone

serio

usly

inju

red/

kille

d1.

42 (9

5% C

I 0.8

8–2.

28)

1.40

(95%

CI 0

.86–

2.27

)1.

27 (9

5% C

I 0.7

7–2.

08)

1.25

(95%

CI 0

.76–

2.06

)

Seen

or h

ad to

han

dle

dead

bod

ies (

not

incl

udin

g fu

nera

ls)

1.56

(95%

CI 0

.98–

2.49

)^1.

57 (9

5% C

I 0.9

7–2.

53)^

1.48

(95%

CI 0

.91–

2.41

)1.

50 (9

5% C

I 0.9

2–2.

44)

Clo

se fa

mily

/frie

nd k

illed

by

drun

k dr

iver

0.98

(95%

CI 0

.53–

1.79

)0.

99 (9

5% C

I 0.5

3–1.

85)

0.92

(95%

CI 0

.49–

1.74

)0.

93 (9

5% C

I 0.4

9–1.

77)

Spou

se/p

artn

er/c

hild

die

d1.

47 (9

5% C

I 0.9

0–2.

39)

1.78

(95%

CI 1

.05–

3.03

)*1.

65 (9

5% C

I 0.9

6–2.

83)^

1.65

(95%

CI 0

.96–

2.82

)^

Serio

us o

r life

-thre

aten

ing

illne

ss1.

79 (9

5% C

I 1.0

4–3.

05)*

2.01

(95%

CI 1

.14–

3.54

)*2.

00 (9

5% C

I 1.1

2–3.

55)*

1.96

(95%

CI 1

.09–

3.51

)*

Forc

ed to

hav

e se

x ag

ains

t will

1.74

(95%

CI 1

.09–

2.77

)*1.

72 (9

5% C

I 1.0

6–2.

79)*

1.58

(95%

CI 0

.97–

2.60

)^1.

55 (9

5% C

I 0.9

4–2.

57)^

Fond

led

unde

r for

ce o

r thr

eat

1.57

(95%

CI 0

.99–

2.50

)^1.

48 (9

5% C

I 0.9

2–2.

40)

1.29

(95%

CI 0

.78–

2.13

)1.

26 (9

5% C

I 0.7

5–2.

10)

Oth

er si

tuat

ion

with

atte

mpt

ed fo

rce

for

unw

ante

d se

xual

con

tact

2.16

(95%

CI 1

.30–

3.57

)**

2.09

(95%

CI 1

.25–

3.49

)*1.

87 (9

5% C

I 1.1

0–3.

19)*

1.85

(95%

CI 1

.08–

3.16

)*

Atta

cked

with

wea

pon

2.20

(95%

CI 1

.30–

3.72

)**

2.43

(95%

CI 1

.40–

4.19

)*2.

19 (9

5% C

I 1.2

5–3.

82)*

2.15

(95%

CI 1

.23–

3.78

)*

Atta

cked

with

out w

eapo

n an

d se

rious

ly in

jure

d1.

91 (9

5% C

I 1.0

9–3.

34)*

2.11

(95%

CI 1

.18–

3.78

)*1.

84 (9

5% C

I 1.0

1–3.

35)*

1.80

(95%

CI 0

.97–

3.23

)^

Fam

ily m

embe

r bea

ten/

push

ed y

ou h

ard

enou

gh to

cau

se in

jury

2.01

(95%

CI 1

.20–

3.35

)*2.

23 (9

5% C

I 1.3

0–3.

80)*

1.95

(95%

CI 1

.12–

3.38

)*1.

91 (9

5% C

I 1.0

8–3.

34)*

Expe

rienc

ed a

ny o

ther

ext

raor

dina

rily

stre

ssfu

lev

ent

1.63

(95%

CI 0

.98–

2.71

)^1.

73 (9

5% C

I 1.0

2–2.

91)*

1.65

(95%

CI 0

.97–

2.80

)^1.

61 (9

5% C

I 0.9

5–2.

75)^

Aliment Pharmacol Ther. Author manuscript; available in PMC 2011 August 1.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

White et al. Page 20* St

atis

tical

ly si

gnifi

cant

at p

<0.0

5.

**St

atis

tical

ly si

gnifi

cant

at p

<0.0

1.

^ App

roac

h si

gnifi

canc

e (0

.05≤

P≤0.

06).

CI,

conf

iden

ce in

terv

al; I

BS,

irrit

able

bow

el sy

ndro

me;

PTS

D, P

ost-t

raum

atic

stre

ss d

isor

der.

1 Pres

ence

of I

BS

dete

rmin

ed a

ccor

ding

to re

spon

ses t

o th

e B

owel

Dis

orde

r Que

stio

nnai

re (B

DQ

) con

sist

ent w

ith a

dia

gnos

is o

f IB

S pe

r ada

pted

Rom

e II

crit

eria

. (se

e al

so M

etho

ds se

ctio

n)

2 Trau

ma

hist

ory

dete

rmin

ed b

y re

spon

ses t

o th

e Tr

aum

a H

isto

ry Q

uest

ionn

aire

(TH

Q)

3 Pres

ence

of P

TSD

det

erm

ined

by

resp

onse

s to

the

Mis

siss

ippi

Sca

le fo

r Com

bat-R

elat

ed T

raum

a (M

-PTS

D) w

ith sc

ore ≥

107

cons

iste

nt w

ith d

iagn

osis

of P

TSD

.

4 Pres

ence

of d

epre

ssio

n of

at l

east

mod

erat

e se

verit

y de

term

ined

by

resp

onse

s to

the

Bec

k D

epre

ssio

n In

vent

ory-

II (B

DI-

II) w

ith sc

ore ≥

20.

Aliment Pharmacol Ther. Author manuscript; available in PMC 2011 August 1.