combat-related stress in soldiers increases segmental intestinal permeability

1
AGA Abstracts to discriminate correctly between 30 vs 34 mm Hg distensions) and perceptual response bias (the tendency to label all sensations regardless of stimulus strength as painful). Results: AML pain thresholds and response bias differed between those with and without Somatization Disorder as well as those who reported normal vs excess somatic symptoms on the BSI and Prime MD (see Table). These were the only scales that included GI co-morbid symptoms, and after excluding those items the association with symptom amplification disappeared. No differences were found between groups on neurosensitivity. Conclusion: High co- morbidity is related to increased visceral hypersensitivity. The latter is not explained by increased neurosensitivity but seems to be related to perceptual response bias (i.e., the tendency to report any stimulus as painful). Interestingly, response bias was only related to co-morbid gastrointestinal symptoms but not non-gastrointestinal symptoms. These findings suggest that this symptom amplification may be specific to the intestine. Studies are needed to assess if response bias in other locations such as the skin can explain the heightened co- morbidity of non-GI symptoms in IBS. [Supported by R01DK31369 and UL1RR025747] *p<.05 491 Combat-Related Stress in Soldiers Increases Segmental Intestinal Permeability Xinhua Li, Yang Cao, Enci Mary Kan, Jia Lu, Reuben K. Wong, Maliha Shaikh, Khek Yu Ho, Clive H. Wilder-Smith Background and aims Stress is widely accepted as a trigger for functional as well as inflammat- ory GI disorders. Animal stress models have demonstrated increased intestinal permeability (IP) and immune activation as mechanisms underlying visceral hypersensitivity and GI dysfunction. However, it is difficult to replicate these findings in humans. Soldiers have considerable real-life, mixed physical and psychological stress as well as a high incidence of GI symptoms, they represent a unique setting for the study of stress on GI function. We therefore investigated the effect of chronic intense stress on IP and systemic inflammatory markers in commando troops. Methods Male commando troops (n=37, 19-23y) in a period of rest and in the final days of 5-week intense combat exercises underwent testing for segmental IP using sucrose, mannitol (M), lactulose (L), and sucralose ingestion and measure- ment of urinary excretion/oral dose. Serum cortisol, IL-6 and TNFα were quantified. GI symptoms (IBS-SSS), stress (PSS-10), anxiety and depression (HAD) were assessed by ques- tionnaires. Statistical analysis was by ANOVA and Pearson's Correlation coefficient (r) tests, means ± SE are shown. Results: Soldiers during combat stress showed higher stress (19.05±1.33 vs. 13.22±1.04, p<0.01), anxiety (8.43±0.61 vs. 3.55±0.41, p<0.01), depression (6.22±0.74 vs. 3.14±0.57, p<0.01), and IBS-SSS score (73±8.70 vs. 47±6.19, p=0.02) than in the resting period. The IBS-SSS scores correlated with depression (r=0.41, p=0.01) and stress (r=0.40, p=0.01) ratings. Gastroduodenal and colonic permeability increased in soldiers during stress compared to rest, as assessed by urinary sucrose (1.05±0.18% vs. 0.41±0.05%, p<0.01) and sucralose (1.97±0.09% vs. 0.66±0.07, p<0.01) respectively. Small intestinal permeability assessed by the L/M ratio was greater during the stress period in soldiers with IBS-SSS75 (threshold of IBS) than in those with IBS-SSS<75 (0.119±0.008 vs. 0.097±0.004, p=0.01). Soldiers under stress have higher serum cortisol (567.46±15.32 vs. 512.32±18.89 nmol/L, p=0.03), IL-6 (2.56±0.62 vs. 1.02±0.29 pg/ml, p<0.01) and TNFα (7.24±1.59 vs. 2.02±0.49 pg/ml, p<0.01) than during rest. Conclusion: Chronic combat stress induced significant GI symptoms, increased gastroduodenal and colonic permeability as well as systemic inflammatory markers. Soldiers with greater GI symptoms during stress also showed increased small intestinal permeability. As increased IP has been associated with deleterious immune responses, visceral hypersensitivity and GI dysfunction, it will be important to define and implement pre-emptive measures in similar stress situations. This human study provides a unique confirmation of data from earlier animal models and validates the assump- tion that chronic stress in humans can modulate IP. Grant support by Defence Science & Technology Agency (DSTA), Singapore 492 Cognitive Behavior Therapy for Children With Functional Abdominal Pain: Preliminary Results of a Randomized Controlled Trial Shelley van der Veek, Bert Derkx, Else de Haan, Marc A. Benninga, Frits Boer Background: Functional abdominal pain (FAP) is a common complaint in children and adolescents. Three previous randomized controlled trials (RCT) showed that cognitive behavior therapy (CBT) is an effective treatment for children with FAP. However, these studies suffered from methodological flaws like small sample sizes and high drop-out rates. Aim: to investigate 1) the effectiveness of CBT compared to medical care (MC) on pain symptoms in a large RCT, and 2) the effectiveness of CBT compared to MC in reducing symptoms of anxiety, depression, disability due to FAP, other somatic complaints and quality of life. Methods: A total of 104 children were randomized to CBT or MC over a three year period. Both treatments consisted of 6 weekly sessions with a trained masters-level psycholo- gist in the CBT arm and a pediatric gastroenterologist/pediatric resident in the MC arm. Data were collected pre- and post-treatment and at 6 and 12 months follow-up. As at the S-94 AGA Abstracts time of the conference follow-up data will not be available yet, only complete pre- to post- treatment data were used in the analyses (N=88). Repeated measures ANOVAs were used to analyze differences in effectiveness between treatment conditions for all outcome measures. Additionally, it was calculated what percentage of children was pain free after treatment or had decreased 2 standard deviations in pain, in accordance with Jacobsen and Truax's criterion of clinical significant change. Results: Children in both treatment conditions improved significantly in their level of abdominal pain from pre- to post-treatment (child report: p<.001; parent report: p <.001). CBT was equally effective as MC in improving abdominal pain, according to both child and parent report (p for time x treatment interaction respectively p=.421 and p=.218). According to child report, 20.9% of children receiving CBT and 8.9% of children receiving MC were pain free after 6 weeks of treatment. According to parent report, this percentage was 23.3% for CBT and 13.6% for MC. According to Jacobsen and Truax's criterion, 25.6% of children reported clinical significant change in the CBT condition, versus 11.1% in the MC condition. These percentages were 37.2% versus 20.5% for parent report. Concerning the other outcome measures, only for social anxiety a significant interaction effect was found, showing that CBT was superior to MC in reducing symptoms of social anxiety (child report: p=.037; parent report: p=.033). Conclusions: Six weekly sessions of either CBT or MC both cause a significant decrease in abdominal pain and co-morbid complaints. CBT does not seem to be superior to MC over this short time period, except for it's effects on co-morbid symptoms of social anxiety. This shows that anxiety might be a moderator of treatment effectiveness, which highlights the value of investigating which treatment works best for which child. 493 Do Symptoms of Lactose Intolerance Reveal a Somatoform Disorder? Carolina Tomba, Annarita Baldassarri, Marina Coletta, Bruno M. Cesana, Guido Basilisco Symptoms of lactose intolerance such as abdominal pain and bloating are often attributed to lactose malabsorption and treated with elimination diets that increase the risk of calcium deficiency. However, psychological factors may play a role in altered symptom perception. Aim: To assess the relationship between the symptoms of lactose intolerance during a lactose hydrogen breath test and the psychological profiles of patients with and without lactose malabsorption. Methods: One hundred and two consecutive patients (77 females; median age 36 years) underwent a 15 g-lactose hydrogen breath test because of suspected lactose malabsorption; 43% fulfilled the Rome III diagnostic criteria for irritable bowel syndrome. The patients recorded the presence and severity of five symptoms of lactose intolerance (pain, nausea, bloating, borborygmi, flatulence) during the test on 10 cm visual analogue scales. A psychological symptom checklist (SCL-90R) assessed the severity of somatisation, anxiety, depression, and the global severity index (GSI). Lactose intolerance was defined as an overall severity of >7 cm, and a normalised SCL-90R cut-off score of 63 identified cases of significant psychopathology. Lactose malabsorption was defined as a >10 ppm increase in baseline breath hydrogen in the three hours after lactose ingestion. Non- parametric tests were used for the univariate analysis; the multivariate analysis included the presence/absence of lactose malabsorption and significant psychopathology. Data are mean values ± SD. Results: Lactose malabsorption and intolerance were diagnosed in 33% and 29% of the patients. The two conditions were not associated (P=0.64) and the severity of intolerance was not significantly higher in the patients with malabsorption (5.37±8.42 vs 4.71±5.81; P=0.97). Univariate analysis revealed that the intolerant patients showed significantly greater somatisation (64±9.16 vs 57.99±7.38; P=0.0009), anxiety (59.67±7.6 vs 56.14±7.04; P= 0.04) and GSI (60.07±8.08 vs 56.19±7.48; P=0.02). Multivariate analysis showed that altered somatisation significantly increased the risk of intolerance (odds ratio 4.184; 1.704-10.309), whereas the effects of the other psychological variables and the presence of lactose malabsorp- tion were not significant. The patients with somatisation more frequently reported the presence of three or more symptoms of lactose intolerance (62% vs 20%; P=0.0001). Conclusions: The symptoms of lactose intolerance during hydrogen breath testing are unre- lated to lactose malabsorption, but reflect a somatoform disorder. 494 How Do Gastric Sensitivity, Abuse History, Psychological Factors, Somatic Symptom Reporting and Quality of Life Interact in Functional Dyspepsia? Lukas Van Oudenhove, Michael Jones, Rita Vos, Lieselot Holvoet, Jan F. Tack Background Functional Dyspepsia (FD), like other functional GI disorders, is likely to be the result of complex interactions between biological, psychological and social factors (Drossman 2006). More specifically, gastric sensorimotor function, abuse history, ‘state’ and ‘trait’ psychosocial factors and ‘somatization’ (a general tendency towards somatic symptom reporting) all play a role in FD and its associated poor quality of life, but the exact nature of their interplay remains poorly understood (Van Oudenhove & Aziz 2009, Van Oudenhove et al 2010). A comprehensive model of how these factors interact has not been tested before. Aim To test a comprehensive a priori hypothesized model of interactions between gastric sensitivity, ‘trait’ and ‘state’ psychosocial factors, somatic symptom reporting and quality of life in FD. The model was based on evidence from the literature as well as previous general linear model analyses on the current data set. Methods In 259 tertiary care FD patients, we studied gastric sensitivity with barostat. We measured abuse history (sexual and physical in childhood and adulthood), ‘trait’ (alexithymia, trait anxiety) & ‘state’ (positive & negative affect, depression, panic disorder) psychological factors, somatic symptom reporting variables (‘somatization’, dyspepsia, IBS & fatigue symptoms) and quality of life (physical, mental) using validated self-report questionnaires. Confirmatory factor analysis (CFA) was used to reduce the number of variables and to assess whether the a priori hypothesized latent constructs (‘abuse’, ‘personality’, ‘state negative affect’ and ‘somatic symptom reporting’) are adequately represented in the model. Structural equation modelling (SEM) was used to test the a priori hypothesized relationships between these latent constructs and the observed variables gastric sensitivity, physical and mental quality of life. Results The CFA had a good fit (C min /DF=2.0, RMSEA=0.63), confirming that the a priori hypothesized latent constructs are adequately represented. Figure 1 shows the SEM results; this model also fits the data well (C min /DF=1.54, RMSEA=0.46). Conclusion We present the first comprehensive model elucidating the complex interactions between gastric sensitivity, abuse history, ‘state’ and

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Page 1: Combat-Related Stress in Soldiers Increases Segmental Intestinal Permeability

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bst

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sto discriminate correctly between 30 vs 34 mm Hg distensions) and perceptual responsebias (the tendency to label all sensations regardless of stimulus strength as painful). Results:AML pain thresholds and response bias differed between those with and without SomatizationDisorder as well as those who reported normal vs excess somatic symptoms on the BSI andPrime MD (see Table). These were the only scales that included GI co-morbid symptoms,and after excluding those items the association with symptom amplification disappeared.No differences were found between groups on neurosensitivity. Conclusion: High co-morbidity is related to increased visceral hypersensitivity. The latter is not explained byincreased neurosensitivity but seems to be related to perceptual response bias (i.e., thetendency to report any stimulus as painful). Interestingly, response bias was only related toco-morbid gastrointestinal symptoms but not non-gastrointestinal symptoms. These findingssuggest that this symptom amplification may be specific to the intestine. Studies are neededto assess if response bias in other locations such as the skin can explain the heightened co-morbidity of non-GI symptoms in IBS. [Supported by R01DK31369 and UL1RR025747]

*p<.05

491

Combat-Related Stress in Soldiers Increases Segmental Intestinal PermeabilityXinhua Li, Yang Cao, Enci Mary Kan, Jia Lu, Reuben K. Wong, Maliha Shaikh, Khek YuHo, Clive H. Wilder-Smith

Background and aims Stress is widely accepted as a trigger for functional as well as inflammat-ory GI disorders. Animal stress models have demonstrated increased intestinal permeability(IP) and immune activation as mechanisms underlying visceral hypersensitivity and GIdysfunction. However, it is difficult to replicate these findings in humans. Soldiers haveconsiderable real-life, mixed physical and psychological stress as well as a high incidenceof GI symptoms, they represent a unique setting for the study of stress on GI function. Wetherefore investigated the effect of chronic intense stress on IP and systemic inflammatorymarkers in commando troops. Methods Male commando troops (n=37, 19-23y) in a periodof rest and in the final days of 5-week intense combat exercises underwent testing forsegmental IP using sucrose, mannitol (M), lactulose (L), and sucralose ingestion and measure-ment of urinary excretion/oral dose. Serum cortisol, IL-6 and TNFα were quantified. GIsymptoms (IBS-SSS), stress (PSS-10), anxiety and depression (HAD) were assessed by ques-tionnaires. Statistical analysis was by ANOVA and Pearson's Correlation coefficient (r) tests,means ± SE are shown. Results: Soldiers during combat stress showed higher stress(19.05±1.33 vs. 13.22±1.04, p<0.01), anxiety (8.43±0.61 vs. 3.55±0.41, p<0.01), depression(6.22±0.74 vs. 3.14±0.57, p<0.01), and IBS-SSS score (73±8.70 vs. 47±6.19, p=0.02) thanin the resting period. The IBS-SSS scores correlated with depression (r=0.41, p=0.01) andstress (r=0.40, p=0.01) ratings. Gastroduodenal and colonic permeability increased in soldiersduring stress compared to rest, as assessed by urinary sucrose (1.05±0.18% vs. 0.41±0.05%,p<0.01) and sucralose (1.97±0.09% vs. 0.66±0.07, p<0.01) respectively. Small intestinalpermeability assessed by the L/M ratio was greater during the stress period in soldiers withIBS-SSS≥75 (threshold of IBS) than in those with IBS-SSS<75 (0.119±0.008 vs. 0.097±0.004,p=0.01). Soldiers under stress have higher serum cortisol (567.46±15.32 vs. 512.32±18.89nmol/L, p=0.03), IL-6 (2.56±0.62 vs. 1.02±0.29 pg/ml, p<0.01) and TNFα (7.24±1.59 vs.2.02±0.49 pg/ml, p<0.01) than during rest. Conclusion: Chronic combat stress inducedsignificant GI symptoms, increased gastroduodenal and colonic permeability as well assystemic inflammatory markers. Soldiers with greater GI symptoms during stress also showedincreased small intestinal permeability. As increased IP has been associated with deleteriousimmune responses, visceral hypersensitivity and GI dysfunction, it will be important todefine and implement pre-emptive measures in similar stress situations. This human studyprovides a unique confirmation of data from earlier animal models and validates the assump-tion that chronic stress in humans can modulate IP. Grant support by Defence Science &Technology Agency (DSTA), Singapore

492

Cognitive Behavior Therapy for Children With Functional Abdominal Pain:Preliminary Results of a Randomized Controlled TrialShelley van der Veek, Bert Derkx, Else de Haan, Marc A. Benninga, Frits Boer

Background: Functional abdominal pain (FAP) is a common complaint in children andadolescents. Three previous randomized controlled trials (RCT) showed that cognitivebehavior therapy (CBT) is an effective treatment for children with FAP. However, thesestudies suffered from methodological flaws like small sample sizes and high drop-out rates.Aim: to investigate 1) the effectiveness of CBT compared to medical care (MC) on painsymptoms in a large RCT, and 2) the effectiveness of CBT compared to MC in reducingsymptoms of anxiety, depression, disability due to FAP, other somatic complaints and qualityof life. Methods: A total of 104 children were randomized to CBT or MC over a three yearperiod. Both treatments consisted of 6 weekly sessions with a trained masters-level psycholo-gist in the CBT arm and a pediatric gastroenterologist/pediatric resident in the MC arm.Data were collected pre- and post-treatment and at 6 and 12 months follow-up. As at the

S-94AGA Abstracts

time of the conference follow-up data will not be available yet, only complete pre- to post-treatment data were used in the analyses (N=88). Repeated measures ANOVAs were usedto analyze differences in effectiveness between treatment conditions for all outcome measures.Additionally, it was calculated what percentage of children was pain free after treatment orhad decreased 2 standard deviations in pain, in accordance with Jacobsen and Truax'scriterion of clinical significant change. Results: Children in both treatment conditionsimproved significantly in their level of abdominal pain from pre- to post-treatment (childreport: p<.001; parent report: p <.001). CBT was equally effective as MC in improvingabdominal pain, according to both child and parent report (p for time x treatment interactionrespectively p=.421 and p=.218). According to child report, 20.9% of children receivingCBT and 8.9% of children receiving MC were pain free after 6 weeks of treatment. Accordingto parent report, this percentage was 23.3% for CBT and 13.6% for MC. According toJacobsen and Truax's criterion, 25.6% of children reported clinical significant change in theCBT condition, versus 11.1% in the MC condition. These percentages were 37.2% versus20.5% for parent report. Concerning the other outcome measures, only for social anxietya significant interaction effect was found, showing that CBT was superior to MC in reducingsymptoms of social anxiety (child report: p=.037; parent report: p=.033). Conclusions: Sixweekly sessions of either CBT or MC both cause a significant decrease in abdominal painand co-morbid complaints. CBT does not seem to be superior to MC over this short timeperiod, except for it's effects on co-morbid symptoms of social anxiety. This shows thatanxiety might be a moderator of treatment effectiveness, which highlights the value ofinvestigating which treatment works best for which child.

493

Do Symptoms of Lactose Intolerance Reveal a Somatoform Disorder?Carolina Tomba, Annarita Baldassarri, Marina Coletta, Bruno M. Cesana, Guido Basilisco

Symptoms of lactose intolerance such as abdominal pain and bloating are often attributedto lactose malabsorption and treated with elimination diets that increase the risk of calciumdeficiency. However, psychological factors may play a role in altered symptom perception.Aim: To assess the relationship between the symptoms of lactose intolerance during a lactosehydrogen breath test and the psychological profiles of patients with and without lactosemalabsorption. Methods: One hundred and two consecutive patients (77 females; medianage 36 years) underwent a 15 g-lactose hydrogen breath test because of suspected lactosemalabsorption; 43% fulfilled the Rome III diagnostic criteria for irritable bowel syndrome.The patients recorded the presence and severity of five symptoms of lactose intolerance(pain, nausea, bloating, borborygmi, flatulence) during the test on 10 cm visual analoguescales. A psychological symptom checklist (SCL-90R) assessed the severity of somatisation,anxiety, depression, and the global severity index (GSI). Lactose intolerance was defined asan overall severity of >7 cm, and a normalised SCL-90R cut-off score of 63 identified casesof significant psychopathology. Lactose malabsorption was defined as a >10 ppm increasein baseline breath hydrogen in the three hours after lactose ingestion. Non- parametric testswere used for the univariate analysis; the multivariate analysis included the presence/absenceof lactose malabsorption and significant psychopathology. Data are mean values ± SD.Results: Lactose malabsorption and intolerance were diagnosed in 33% and 29% of thepatients. The two conditions were not associated (P=0.64) and the severity of intolerancewas not significantly higher in the patients with malabsorption (5.37±8.42 vs 4.71±5.81;P=0.97). Univariate analysis revealed that the intolerant patients showed significantly greatersomatisation (64±9.16 vs 57.99±7.38; P=0.0009), anxiety (59.67±7.6 vs 56.14±7.04; P=0.04) and GSI (60.07±8.08 vs 56.19±7.48; P=0.02). Multivariate analysis showed that alteredsomatisation significantly increased the risk of intolerance (odds ratio 4.184; 1.704-10.309),whereas the effects of the other psychological variables and the presence of lactose malabsorp-tion were not significant. The patients with somatisation more frequently reported thepresence of three or more symptoms of lactose intolerance (62% vs 20%; P=0.0001).Conclusions: The symptoms of lactose intolerance during hydrogen breath testing are unre-lated to lactose malabsorption, but reflect a somatoform disorder.

494

How Do Gastric Sensitivity, Abuse History, Psychological Factors, SomaticSymptom Reporting and Quality of Life Interact in Functional Dyspepsia?Lukas Van Oudenhove, Michael Jones, Rita Vos, Lieselot Holvoet, Jan F. Tack

Background Functional Dyspepsia (FD), like other functional GI disorders, is likely tobe the result of complex interactions between biological, psychological and social factors(Drossman 2006). More specifically, gastric sensorimotor function, abuse history, ‘state’ and‘trait’ psychosocial factors and ‘somatization’ (a general tendency towards somatic symptomreporting) all play a role in FD and its associated poor quality of life, but the exact natureof their interplay remains poorly understood (Van Oudenhove & Aziz 2009, Van Oudenhoveet al 2010). A comprehensive model of how these factors interact has not been tested before.Aim To test a comprehensive a priori hypothesized model of interactions between gastricsensitivity, ‘trait’ and ‘state’ psychosocial factors, somatic symptom reporting and quality oflife in FD. The model was based on evidence from the literature as well as previous generallinear model analyses on the current data set. Methods In 259 tertiary care FD patients,we studied gastric sensitivity with barostat. We measured abuse history (sexual and physicalin childhood and adulthood), ‘trait’ (alexithymia, trait anxiety) & ‘state’ (positive & negativeaffect, depression, panic disorder) psychological factors, somatic symptom reporting variables(‘somatization’, dyspepsia, IBS & fatigue symptoms) and quality of life (physical, mental)using validated self-report questionnaires. Confirmatory factor analysis (CFA) was used toreduce the number of variables and to assess whether the a priori hypothesized latentconstructs (‘abuse’, ‘personality’, ‘state negative affect’ and ‘somatic symptom reporting’) areadequately represented in the model. Structural equation modelling (SEM) was used to testthe a priori hypothesized relationships between these latent constructs and the observedvariables gastric sensitivity, physical and mental quality of life. Results The CFA had a goodfit (Cmin/DF=2.0, RMSEA=0.63), confirming that the a priori hypothesized latent constructsare adequately represented. Figure 1 shows the SEM results; this model also fits the datawell (Cmin/DF=1.54, RMSEA=0.46). Conclusion We present the first comprehensive modelelucidating the complex interactions between gastric sensitivity, abuse history, ‘state’ and