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Beck Depression Inventory; HPA hypothalamic pi- ... link between the CNS and the gut, and, as such, they are important candidates for mediating abnormal brain-gut interactions in ..... Saliva free cortisol was used as a measure of HPA axis function- ing. .... There were 12 missing data points because of insuf- ficient saliva ...

Psychological and Physiological Responses to Postprandial Mental Stress in Women With the Irritable Bowel Syndrome SIGRID ELSENBRUCH, PHD,1 WILLIAM R. LOVALLO, PHD,

AND

WILLIAM C. ORR, PHD

Objective: To investigate the psychological (affective and symptomatic) and physiological (autonomic and cortisol) responses to postprandial mental stress in women with irritable bowel syndrome (IBS). It was hypothesized that patients with IBS would show exaggerated autonomic and cortisol responses to the psychological stressor and that the stressor would enhance gastrointestinal symptoms. Method: Twenty-four women with IBS and 20 healthy women participated in the two-day study protocol. Both days were identical, with the exception that on one day, a stressful mental task was completed after ingestion of a standard meal. Heart rate variability, cortisol, affective, and symptomatic responses were measured before and after application of the stressor. Results: Patients with IBS demonstrated increased negative affect at baseline and in response to the stressor. Gastrointestinal symptoms were not affected by the stressor. Appraisal of the stressor by patients with IBS was not different from that of controls. There were no group differences in the autonomic response to the stressor. There was no overall cortisol response to the stressor in either group. Conclusions: Patients with IBS respond with greater negative affect to postprandial psychological stress as well as to food intake alone, and they can be distinguished from controls on the basis of self-report data. Patients with IBS cannot be differentiated from controls on the basis of the pattern of changes in sympathetic activation after the mental stressor. The stressor used in this study did not elicit a cortisol response in either group. Key words: Irritable bowel syndrome; autonomic nervous system; cortisol; mental stress; heart rate variability; functional bowel disorder.

IBS ⫽ irritable bowel syndrome; HRV ⫽ heart rate variability; LF ⫽ low frequency; HF ⫽ high frequency; GI ⫽ gastrointestinal; ANS ⫽ autonomic nervous system; CNS ⫽ central nervous system; ECG ⫽ electrocardiogram; SEM ⫽ standard error of the mean; BDI ⫽ Beck Depression Inventory; HPA ⫽ hypothalamic pituitary adrenal.

IBS is one of the most common functional gastrointestinal disorders, characterized by abdominal pain associated with altered bowel habit (ie, diarrhea and/or constipation) (1, 2). Much evidence suggests that the pathogenesis of IBS involves abnormal braingut interactions, characterized by a hyperresponsiveness and/or a hypersensitivity (3–5). However, it is unclear whether this occurs at the level of the gut, the ANS, or the CNS (3–10). There is evidence to support the importance of both visceral stimuli (eg, colonic distention) and nonvisceral stimuli (eg, psychological stressors) (3–10). Therefore, it is conceptually possible that IBS pathophysiology involves abnormal afferent (ascending) or efferent (descending) mechanisms. The autonomic and endocrine systems represent the

From the Lynn Institute for Healthcare Research (S.E. and W.C.O.) and VA Medical Center (W.R.L.), Oklahoma City, OK. Address correspondence to: William C. Orr, PhD, Lynn Institute for Healthcare Research, 5300 N. Independence, Suite 130, Oklahoma City, OK 73112. Email: [email protected] Received for publication January 12, 2000; revision received December 14, 2000. 1 Current affiliation: Institute for Medical Psychology, University Clinic of Essen, Germany.

Psychosomatic Medicine 63:805– 813 (2001) 0033-3174/01/6305-0805 Copyright © 2001 by the American Psychosomatic Society

link between the CNS and the gut, and, as such, they are important candidates for mediating abnormal brain-gut interactions in IBS. In fact, several studies have documented autonomic abnormalities in patients with IBS, whereas endocrine abnormalities are less well studied (6, 7, 11–21). Higher cortical and limbic brain areas can modulate the hypothalamic and brain stem areas that control autonomic and endocrine outflow. In light of numerous reports of significant psychogenic components of this functional disorder, this begs the question of the role of psychological and emotional factors in autonomic dysfunction previously found in response to various stimuli in patients with IBS. If, in fact, descending mechanisms play a role in physiologic responses to various stimuli, this modulation would be particularly prominent during psychological stress. The specific aim of this study was to investigate the autonomic, cortisol, affective, and symptomatic responses to postprandial psychological stress in patients with IBS compared with controls. The rationale for applying a psychological stressor was to activate the descending mechanism of hypothalamic activation in patients with IBS. In doing so, the goal was to elucidate the psychological and physiological components of abnormal brain-gut interactions in IBS. It was hypothesized that exposure to a psychological stressor, presented during the postprandial period, would be associated with abnormal autonomic and cortisol responses and gastrointestinal symptoms in patients with IBS. METHODS Subject Recruitment and Screening Procedure The majority of patients with IBS were recruited from an existing database from the clinical trials program of the Institute (excluding

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S. ELSENBRUCH et al. individuals currently on study medication). Controls and a minor portion of patients with IBS were recruited through public advertisement. Care was taken to ensure that participants had little experience as research subjects (other than in clinical trials). Importantly, the main goal of the study (ie, stress responses) was not disclosed during recruitment and screening. Instead, the stressor was described as a neuropsychological task that required concentration and fast responding. The screening procedure consisted of a structured phone screening and a personal interview at the Institute, both conducted by the first author. During the phone screen, it was evaluated whether individuals met the major criteria for eligibility. These included that individuals were female, between 21 and 50 years of age, and without any evidence of gastrointestinal diseases (other than IBS for the IBS group), autonomic or cardiovascular conditions, chronic neurologic conditions, current psychiatric conditions, or chronic medications known to affect the parameters collected in this study, including psychotropic medications such as antidepressants. Short-acting IBS medications were not considered to be exclusionary. It was further confirmed that patients with IBS met the Rome criteria for IBS and had received a diagnosis of IBS at least one year before the study (22). During the personal interview, subjects completed a number of questionnaires that assessed demographic and medical information. In addition, chronic gastrointestinal symptoms over the preceding three months were assessed both in healthy individuals and patients with IBS with an ad hoc questionnaire (ie, a total of 17 upper and lower GI symptoms rated on a scale from 0 ⫽ never experienced to 3 ⫽ experienced more than twice per week). One individual was excluded from participation in the control group because of the presence of GI symptoms. Participants also completed the BDI, and individuals with a total score greater than 14 were excluded (this occurred in the case of one patient with IBS). Several blood pressure measurements were taken to ensure normal blood pressures, and one individual was excluded from the control group because of pressures greater than 140/90. ECG recordings were performed with a Burdick E350I Electrocardiograph. Recordings that were identified as abnormal by the computer interpretation were evaluated by a collaborating physician. No individual was excluded because of evidence of ECG abnormalities. The study protocol was approved by the Institutional Review

TABLE 1.

Board of Integris Baptist Medical Center of Oklahoma. All participants gave informed written consent before entering the study and were paid for their participation.

Sample Characteristics Demographic and medical characteristics of participants are shown in Table 1. In addition, patients with IBS had significantly higher scores on all dimensions of the Symptom Check List (SCL) as well as on its global indices (23). On the basis of the author’s nonpatient female norms, eight patients with IBS but none of the women in the control group were at positive risk for a psychiatric disorder (23). With regard to the IBS symptom profile for women in the IBS group, on average, patients had begun experiencing IBS symptoms at age 18, had suffered an average of 13.3 years, and had sought medical attention for their IBS symptoms an average of 9.5 times. Patients reported experiencing pain on an average of 2.7 days per week, and 50% of patients reported that their pain was typically “quite severe” or “very severe” and that their IBS was interfering with their personal or professional lives “quite a lot” or “completely.” With regard to stool patterns, 12 of the patients reported constipation alone, whereas the remaining patients reported symptoms of either diarrhea alone or alternating diarrhea and constipation.

Study Protocol All participants were studied in two study sessions accomplished on two separate days in counterbalanced order. Both sessions were identical, with the exception that on one day subjects completed a stressful task (stress day), whereas on the other day they underwent a postprandial passive relaxation period (rest day). Three 30-minute ECG recordings were accomplished on each day: (1) a fasting baseline, after which participants ingested a standardized, solid-liquid meal containing a total of 715 calories (26 g fat, 87 g carbohydrates, 21 g protein); (2) a stress or rest recording period; and (3) a recovery recording. Symptomatic and affective responses and saliva samples were collected immediately on arrival to the lab, after the baseline recording, after the meal, after the stressor/rest period, and after the recovery recording.

Demographic Characteristics of Women in the IBS and Control Groups

Age, mean (SEM) Ethnicity, white % (n) Married, % (n) Divorced, % (n) College degree, % (n) Smoker, % (n) Body mass index, mean (SEM) Daily caffeine intake mg, mean (SEM) Weekly alcoholic beverages, mean (SEM) Birth control, % (n) Postmenopausal, % (n) Systolic BP, mean (SEM) Diastolic BP, mean (SEM) BDI score, mean (SEM) GI symptom frequency, mean (SEM)

IBS (n ⫽ 24)

Control (n ⫽ 20)

p

32.8 (1.4) 95.8 (23) 70.8 (17) 20.8 (5) 41.7 (10) 12.5 (3) 24.7 (0.8) 189.6 (37.4) 1.5 (0.4) 42.9 (9) 12.5 (3) 110.6 (1.9) 73.8 (1.5) 4.7 (0.7) 22.7 (1.2)

32.5 (1.1) 90.0 (18) 50.0 (10) 15.0 (3) 60.0 (12) 0 23.6 (0.7) 107.3 (25.7) 0.3 (0.2) 40.0 (8) 0 111.8 (2.8) 74.2 (1.9) 1.4 (0.4) 1.1 (0.3)

NS NS NS NS NS NS NS NS p ⬍ .05 NS NS NS NS p ⬍ .001 p ⬍ .001

BP ⫽ blood pressure; BDI ⫽ Beck Depression Inventory; SEM ⫽ standard error of the mean; mg ⫽ milligram; GI ⫽ gastrointestinal; alc. ⫽ alcohol-containing.

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RESPONSES TO POSTPRANDIAL STRESS IN IBS Subjects were required to discontinue medications, including short-acting GI symptom medications such as antacids (but not birth control pills or allergy medications) a minimum of 24 hours before the study sessions. To minimize circadian effects, all recording sessions took place in the afternoon between 12:00 and 18:00, and for each subject the starting time was the same for both sessions. In addition, the two sessions were scheduled no more than seven days apart. During the baseline and recovery periods of both study days, participants watched commercially available videos from the Beautiful Cities of the World series (Madacy Entertainment Group, Inc.), in order to standardize levels of activity. During the passive relaxation period, participants watched a segment of the commercially available video Nature Whispers, Vol. 1 (Madacy Entertainment Group, Inc). No special instructions were given during this period (ie, passive relaxation). To minimize movement-related artifacts and position effects, subjects remained in the supine position with their head and upper body slightly elevated during all recordings. Subjects were monitored from outside the room via a video camera installed in the laboratory to ensure wakefulness and prevent interference with the recordings.

The Stress Task The task was an adapted, specially designed computerized reaction time task with noise “punishment,” based on a variant of the Stroop Color Test. The reaction time task is a previously utilized active avoidance task, which requires fast responses to a visual signal to avoid an aversive auditory signal (24). In its original form, the Stroop Test assesses the ability to shift a perceptual set (25, 26). Because it requires significant concentration and mental effort and has aversive emotional qualities, many investigators have used it as a mental stressor (20, 25, 27). In the present study, subjects were presented with a series of words that appeared every 2 seconds on average, for a duration of 200 Ms, at random intervals. As in the Stroop Color Test, the words depicted various colors, but the color of the letters of each word differed from its actual meaning (eg, the letters of the word “blue” were of red color). The words “red” and “green” were the two target stimuli that required responses. The word “red” appeared in 30% and the word “green” in 25% of cases. The remaining 45% of words acted as “distracters” that required no response (ie, in fact they required response suppression). The target stimulus “red” required fast clicking on a red box on the computer monitor. Failure to respond correctly within 600 Ms was associated with a noise burst of about 70 dB and 2 seconds in duration, which was delivered via a pair of headphones. Failure to respond correctly within 600 Ms by clicking on a green box in response to the target stimulus “green” was associated with a deduction from a “dollar bank.” In an attempt to increase the aversiveness of the task by including elements of unpredictability and uncontrollability, the computer was programmed to deliver a noise in 30% of cases (at random intervals) when the word “red” was presented, regardless of the reaction time of the subject. Similarly, money was deducted in 40% of cases (in random intervals), regardless of reaction time. Participants were further led to believe that they were videotaped during the task, and, in all cases, the investigator was present throughout the task to increase the aversiveness of the situation and ensure compliance with the task instructions.

Dependent Measures HRV analysis was used as a noninvasive, quantitative evaluation of the sympathovagal interaction modulating cardiac function (28 – 30). Physiologically, respiratory sinus arrhythmia and vasomotor waves form the basis of HRV and of the parameters derived from

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spectral analysis of the HRV signal. Respiratory sinus arrhythmia can be defined as the variations in heart rate mediated through alternating increases and decreases in parasympathetic input to the sinus node, which occur at a frequency of 0.15 to 0.5 Hz (ie, the HF band). In addition, a slower rhythm in phase with vasomotor waves exists, and these sympathetically mediated influences affect the heart rate in the frequency range of 0.04 to 0.15 Hz (ie, the LF band). Therefore, the HF bandpower of the HRV power spectrum, defined as the total energy in decibels in the 0.15 to 0.5 Hz frequency, range represents cardiac vagal tone. Conversely, the LF band power indicates mainly sympathetic activity, although minor vagal influences have also been noted in this frequency range. The ratio of the LF and HF components, the LF/HF ratio, is an indicator of sympathovagal balance, with greater values reflecting enhanced overall sympathetic dominance (28 –30). Saliva free cortisol was used as a measure of HPA axis functioning. Saliva has been shown to be a noninvasive specimen source of free cortisol independent of extraneous factors such as saliva flow rate (31, 32). Cortisol is the primary glucocorticoid hormone in humans. Although it is primarily involved in glucose metabolism, its release has been shown to be differentially increased by HPA activation during states of stress (33). Acute increases in cortisol occur in stressful situations that involve ego involvement, novelty, unpredictability, and negative emotions such as fear, anxiety, helplessness, and loss of control (33–35). Affective responses were assessed with the Positive Affectivity/ Negative Affectivity Schedule (PANAS) (36). Symptomatic responses were measured with an ad hoc gastrointestinal symptom questionnaire, which consisted of a variety of upper and lower GI symptoms (ie, heartburn, indigestion, stomach ache, difficulty swallowing, nausea, bloating, lower abdominal pain, gaseousness, belching, stomach fullness, satiety, hunger, and urge to defecate) and used the same rating scale and instructions as the PANAS (ie, present moment ratings on a five-point scale from “very little or not at all” to “extremely”). In order to assess individual’s appraisal of the task characteristics, subjects rated the task’s stressfulness, its aversiveness, and their confidence regarding task performance on five-point rating scales identical to those of the PANAS.

Data Acquisition and Analysis HRV data were derived from the ECG signal, which was recorded with standard Ag/AgCl cutaneous electrodes, applied to the lower left side of the thorax on the mid-axillary line and to the left and right shoulders over the clavicle after preparation of the electrode sites with an abrasive paste and electroconductive gel. ECG data were continuously recorded by use of a computerized data collection system and a bioamplifier (Medtronics). Analog ECG signals underwent A/D conversion with a sampling rate of 6000 Hz and 16-bit resolution, in order to ensure quality signals. Digitized signals were stored on computer hard disk and then archived to CD-ROM for long-term storage. For analysis, the digitized ECG signal were down-sampled to 500 Hz. Computer software (ie, signal processing Toolbox for MATLAB, the Math Works Inc., Natick, MA) was used to perform the R-wave peak identification and the calculation of the beat-to-beat heart rate intervals (ie, R-R intervals). The R-R intervals were then resampled at 2 Hz and interpolated by use of weighted averages of beats that fall within the sample interval for the value at a given point in the time series. The HRV was then subjected to overall spectral analysis, yielding the HF band power, the LF band power, and the LF/HF ratio. Saliva samples were collected by use of a commercially available collection device (Salivette®, Sarstedt, Germany), centrifuged, and

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S. ELSENBRUCH et al. stored at ⫺70°C until assayed. Cortisol concentrations were measured by a radioimmunoassay technique with a commercially available kit (Orion Diagnostica, Espoo, Finland) adapted to measure the low cortisol concentrations present in saliva. The actual assays were performed by a laboratory with expertise in the techniques at the Université Libre de Bruxelles in Belgium. PANAS responses on the negative affective items were summed to yield a negative affective score per assessment period. For the present study, the negative affective scores were of primary interest, because several of the positive PANAS items reflect behavioral arousal (eg, “active,” “attentive,” or “active”) and were expected to be influenced by the study design. For symptomatic responses, an average symptom score was computed.

Statistical Analyses The statistical analyses were planned a priori. The design was a three-way mixed, repeated-measures design. Initially, multivariate analysis of variance (MANOVA) with F tests for between-group comparisons were accomplished. Then planned contrasts (ie, paired t tests for within-group comparisons and independent-samples t tests for between-group comparisons) were carried out as follows: To compare the groups at baseline, baseline responses were averaged over both study days, and the effects of the stressor were analyzed by comparing the two study days within each group and then comparing the groups on the stress day. With the exception of baseline comparisons, all comparisons were carried out on delta scores (eg, stress/rest minus baseline and recovery minus stress/rest), as a way to account for individual baseline differences, because the main interest was to investigate response patterns in patients compared with controls with and without the stressor. For assessment of group differences in demographic characteristics and symptom profile and the rating of the task’s characteristics, independent-sample t tests and Fisher’s Exact Test were carried out where appropriate. Correlation analyses were carried out by use of Pearson’s r. In all statistical procedures, the alpha level was set at 0.05.

RESULTS All data are presented as mean ⫾ SEM. Subjective Responses to the Stress Task No significant group differences were found in the appraisal of the task’s characteristics or in the total number of noises delivered (see Table 2). The F test on negative affect showed a significant main effect for Group (F(1, 42) ⫽ 7.9, p ⬍ .01). The MANOVA showed significant effects for Day (␭(2, 42) ⫽ 0.8, p ⬍ .01) and Period (␭(4, 39) ⫽ 0.24, p ⬍ .001), a significant interacTABLE 2.

tion of Day with Period (␭(4, 39) ⫽ 0.6, p ⬍ .001), and a trend for an interaction of Period with Group (␭(4, 39) ⫽ 0.8, p ⫽ .056). In response to the stressor, both groups showed a significant increase in negative affect (within-group comparisons, both p ⬍ .01). However, patients with IBS showed a greater increase in negative affect than controls (p ⬍ .05 for between-group change), as well as a significantly greater decrease in negative affect after the recovery (p ⬍ .05, see Figure 1b). Patients with IBS further reported more negative emotions during baseline (p ⫽ .0505) and after the meal (change from period two to period three betweengroups: p ⬍ .05, see Figure 1a). The F test on gastrointestinal symptoms showed a significant effect for Group (F(1,42) ⫽ 38.5, p ⬍ .001). The MANOVA revealed a significant effect for Period (␭(4, 39) ⫽ 0.6, p ⬍ .01), a significant interaction of Period and Group (␭(4, 39) ⫽ 0.8, p ⬍ .05), and a trend for an effect of Day (␭(1, 42) ⫽ 0.9,p ⬍ .08). The stressor had no significant effects on symptoms in either group. Postprandial negative affect was significantly correlated with postprandial GI symptoms in patients with IBS (r ⫽ .46, p ⬍ .05 for period three; r ⫽ .6, p ⬍ .01 for period four). Patients with IBS reported significantly more GI symptoms at baseline (all p ⬍ .001). Cortisol Results There were 12 missing data points because of insufficient saliva present in the sample, and 19 outliers (defined as values 2.5 standard deviations greater than the group mean) were detected and subsequently deleted. The results showed no main effect for group. The MANOVA revealed significant effects for Day (␭(1, 43) ⫽ 0.9, p ⬍ .05) and Period (␭(4, 31) ⫽ 0.6, p ⬍ .01) and a significant three-way interaction of Day ⫻ Period ⫻ Group (␭(4, 31) ⫽ 0.7, p ⬍ .05). Post hoc within-group comparisons of the change scores between days revealed no significant differences for either group. Between-group comparisons of the means for each measurement period on the stress day showed no group differences, nor did between-group comparisons of the difference scores (ie, pre- vs. poststress). Figure 2 shows the cortisol concentrations on the stress day.

Perceived Task Characteristics and Number of Noises Delivered

Heart Rate and HRV Results Patients with IBS Controls

Stressfulness

Aversiveness

Confidence

Noises

3.1 (0.3) 3.0 (0.2)

2.9 (0.3) 2.9 (0.2)

2.3 (0.4) 2.2 (0.3)

109 (5) 110 (4)

All data are presented as mean (SEM). Items were rated on a one (“very little”) to five (“extremely”) scale. No significant group differences were found.

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The initial MANOVA revealed a significant effect for Period (␭(2, 36) ⫽ 0.1, p ⬍ .001) and a significant interaction of Day and Period (␭(2, 36) ⫽ 0.7, p ⬍ .01). No main effect for Group was found, and planned between-group comparisons revealed no differences between groups in the HRV response to the stressor.

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RESPONSES TO POSTPRANDIAL STRESS IN IBS

Fig. 2.

Fig. 1.

Negative affect on the rest day (a) and stress day (b) in controls and patients with IBS. On the rest day, patients with IBS showed greater negative affect at baseline (*p ⫽ .051) and after the meal (*p ⬍ .05). On the stress day, patients with IBS reported greater negative affect in response to the stressor (⫹p ⬍ .05), and they showed a greater decrease in negative affect after the recovery period (*p ⬍ .05). The data are shown as mean and SEM. Time points 1 and 2 are preprandial; 3 to 5 are postprandial.

Within-group changes, when the rest and stress days were compared, showed a significantly greater increase in heart rate from baseline to stress in both groups (p ⬍ .01 for controls; p ⬍ .05 for IBS, see Table 3). Patients with IBS showed a slight decrease in the LF/HF ratio from baseline to the stress period, which was significantly different from the slight increase ob-

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Salivary cortisol concentrations (ng/ml) in patients with IBS and controls on the stress day. There were no significant differences in the group means for any measurement period, in the between-group change scores (pre- vs. poststress), or in the within-group difference scores comparing the rest and the stress day. Time points 1 and 2 are preprandial; 3 to 5 are postprandial.

served on the rest day (p ⬍ .05 for the change score; see Figure 3b). In addition, several significant differences between the two days were found when the changes from the stress/rest period to the recovery period were compared: Compared with the rest day, there was a significantly greater increase in the LF/HF ratio from the stress to the recovery period in controls (withingroup comparison: p ⬍ .01, see Figure 3a). This did not reach significance in patients with IBS (see Figure 3b). Comparisons of the individual HRV power band revealed a difference between days in the LF band but not the HF band in both groups: There was a greater increase in the LF bandpower from the stress to the recovery period on the stress day (p ⬍ .01 for controls; p ⬍ .1 for IBS). Because of the failure of the stressor to induce an immediate sympathetic response in either group, a dichotomous variable (“aversiveness”) was created on the basis of each subject’s rating of the task aversiveness. Subjects with a rating equal to or greater than three (ie, “moderately,” “quite a bit,” or “extremely”) were classified as perceiving the task as very aversive “HIGH,” whereas those with ratings smaller than three were classified as “LOW.” The rest and stress days were then compared in the individuals in the HIGH group (15 patients with IBS and 10 controls). The results revealed that, compared with the rest period, the stress period was characterized by significantly lower LF band power and LF/HF ratio in this group (both p ⬍ .05). DISCUSSION This investigation addressed brain-gut interactions in patients with IBS by evaluating the psychological (affective and symptomatic) and physiological (auto-

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S. ELSENBRUCH et al. TABLE 3.

Heart Rate Responses to the Stressor

Group

Baseline

Stress

Recovery

Controls Patients with IBS

66.3 (2.0) 69.9 (1.9)

74.6 (2.5)a 78.6 (1.8)a

77.5 (2.4) 81.3 (1.9)

Note: All data are shown as mean (SEM). There were no significant between-group differences. a The change from baseline to stress was significantly greater within each group compared with the rest day (p ⬍ .01 for controls; p ⬍ .05 for patients with IBS).

nomic and cortisol) responses to a postprandial mental stressor in women with IBS compared with controls. The study’s primary goal was to test the hypothesis that, in patients with IBS, autonomic and cortisol responses and symptoms would be enhanced by a mental stressor given during the postprandial period by activating the descending mechanism of autonomic and HPA axis activation. Clearly, the results did not support this hypothesis, because the stressor failed to enhance physiological abnormalities present because of the meal alone (37) or to affect gastrointestinal symptoms. However, the role of postprandial timing in the present results remains unclear. It is quite conceivable that the lack of symptomatic response to the stressor was simply due to the fact that the responses to the meal alone “overshadowed” any reaction to the stressor. Therefore, it would be more appropriate to perform future stress studies exclusively in the fasting state. Furthermore, patients did not differ from controls with regard to ratings of the task’s characteristics: on average, the task was perceived as being moderately stressful and moderately aversive, and little confidence was felt regarding task performance on average. On the other hand, patients with IBS showed a greater negative affective response than controls. The fact that patients with IBS did not perceive the qualities of the task any differently than controls seems to contradict the finding that they showed more negative emotions in response to it. One way to explain this is to suggest that the rating of the task’s characteristics call on cognitive appraisal, rather than emotional processing. On the basis of this notion, these results can be interpreted as evidence that the negative emotional responses of patients with IBS to stressful events are enhanced, whereas their cognitive appraisals are normal. Given the previously documented association of cortisol and negative mood states, it had been anticipated that the stressor would elicit a greater cortisol response in patients with IBS. However, the task was ineffective in eliciting a cortisol response in either group. In addition, the stress task was designed to elicit sympathetic and cardiovascular activation. In-

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deed, the results showed that the stressor was associated with significant elevations in heart rate. However, HRV variables showed no evidence of sympathetic activation in either group during the stress period. Instead, both groups demonstrated enhanced sympathetic activation, indicated by an increased LF/HF ratio, after the termination of the stressor. The literature on the cardiac dynamics during various neuropsychological tasks supports that the task-specific sensory and motor requirements determine cardiac autonomic responses. Tasks, like the one used in the present study, which require complex sensory-motor integration, anticipation of events, and alternating motor inhibition and motor response initiation may not be associated with increased sympathetic outflow to the heart. Instead, after their termination, there can be accelerative recovery, characterized by “rebound” sympathetic dominance (38, 39). This appears to have occurred in the present study, given that, in highly stressed individuals, the results showed decreased sympathetic activity during the stressor, followed by rebound sympathetic activation. Although the current task did involve fast responding, subjects were completely immobile (with the exception of the index finger mouse clicks), and the task also involved complex perceptual components and sensory-motor integration. Thus, the overall motor requirement may not have been strong enough to offset the sensory aspects of the task, and it therefore did not elicit physiological preparation for “fight-or-flight.” In this context, it is also important to mention the relevance of the Stroop task to the subjects. Clearly, although the Stroop is used fairly widely, it is not a social stressor, and one may therefore assume little personal relevance to the subjects. However, in this experiment, social aspects were added—ie, subjects were told that they were being videotaped, and the investigator remained in the laboratory during task performance “to note errors.” Therefore, we conclude that the lack of (immediate) sympathetic response in both groups indicates that the patients are not abnormally reactive to this stressor, rather than suggesting a failure to properly operationalize the stress manipulation. However, the task was clearly not prolonged enough and/or not aversive enough to induce a cortisol response in either group, which constitutes a limitation of this study. Certainly, responses to the Stroop (or the lack thereof) are not necessarily generalizable to other types of stressors, and it is conceivable that patients with IBS are overly responsive to more personally relevant situations. In addition, the present results are probably not generalizable to all patients with IBS, given that the patient selection process in the present study excluded patients with significant psychopa-

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RESPONSES TO POSTPRANDIAL STRESS IN IBS

Changes in LF/HF ratio in controls (a) and patients with IBS (b) on the stress day compared with the rest day. There were no significant group differences. Within-group comparisons showed that, compared with the rest day, there was a significantly greater increase in the LF/HF ratio on the stress day in controls (*p ⬍ .05) from stress/rest to recovery (see panel a). This increase did not reach significance in patients with IBS. There was a significant difference between days in change from baseline to stress in patients with IBS (*p ⬍ .05) (see panel b). The data are shown as mean and SEM.

ment-seeking IBS population (“IBS nonpatients”) with regard to psychological variables. Clearly, further investigation of psychophysiological responses of the IBS population with different types of stressors (particularly social stressors) are clearly needed, and special attention should be given to possible differences among patients with IBS patients who have different degrees of psychopathology (ie, patients with IBS and IBS nonpatients). Despite these limitations, the present task was clearly effective in causing both emotional and cardiovascular changes in both patients with IBS and in controls. Therefore, it was appropriate for the evaluation of this study’s main goal to investigate responses to a psychological challenge in a population of patients presumed to be hyperresponsive to cognitive/ emotional stimuli. The results did not support this hypothesis, because patients with IBS could not be differentiated from controls on the basis of their autonomic and cortisol responses to the mental stressor. The present negative findings are inconsistent with several previous reports that support the connection of stress and GI symptoms in patients with IBS (40 – 44). However, other negative findings have been reported, and the “stress hypothesis” remains controversial (20, 21, 45– 47). For example, rather than causing or exacerbating IBS symptoms, stress may be a consequence of IBS symptoms (45, 48). Alternatively, the attribution of IBS symptoms to stress may partly be a result of the tendency of patients with IBS to search for an explanation of their physical symptoms. In addition, the results of both correlational studies and those applying laboratory stressors are conflicting. Although some studies have reported positive findings, others have not been able to show differences in motility or cardiovascular reactivity to various neuropsychological stress tasks in patients with IBS compared with controls (20, 21, 42– 44, 46, 47). Although patients with IBS do appear to be emotionally more responsive to a variety of internal and external events, these affective responses do not appear to be closely related to autonomic or cortisol abnormalities. Instead, disordered affect is consistent with the increased incidence of psychopathology and may determine other aspects of IBS such as illness experience, healthcare seeking, and coping strategies (49, 50).

thology (ie, with a current psychiatric disorder or a BDI score greater than 14). This was done to avoid confounding of the results by psychopathology. Thus, the present sample, although all treatment-seeking patients, may be more representative of the non–treat-

The authors thank Dr. Mireille Baleriaux from the Experimental Medicine Laboratory of the University of Brussels and Barbara McKey from the Behavioral Sciences Lab at the VA Medical Center in Oklahoma City for their help with the cortisol analyses. We also thank Drs. Zhishun Wang and Jiande Chen from the Univer-

Fig. 3.

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