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The gastrointestinal (GI) tract is part of the digestive system, which processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) in foods that are eaten and helps pass waste material out of the body. The GI tract includes the stomach and intestines (bowels). The stomach is a J-shaped organ in the upper abdomen. Food moves from the throat to the stomach through a hollow, muscular tube called the esophagus. After leaving the stomach, partly-digested food passes into the small intestine and then into the large intestine (colon). The last 6 inches of the large intestine are the rectum and the anal canal. The anal canal ends at the anus (the opening of the large intestine to the outside of the body).


Anatomy of the lower digestive system, showing the colon and other organs.
GI complications are common in cancer patients. Complications are medical problems that occur during a disease, or after a procedure or treatment. They may be caused by the disease, procedure, or treatment, or may have other causes. This summary describes the following GI complications and their causes and treatments:
This summary is about GI complications in adults with cancer. Treatment of GI complications in children is different than treatment for adults.

Gastrointestinal specific anxiety in irritable bowel syndrome: validation of the Japanese version of the visceral sensitivity index for university students

Tatsuo Saigo12Jun Tayama1Toyohiro Hamaguchi3Naoki Nakaya4Tadaaki Tomiie5Peter J Bernick1Motoyori Kanazawa6Jennifer S Labus7Bruce D Naliboff7,Susumu Shirabe1 and Shin Fukudo6*

Center for Health and Community Medicine, Nagasaki University, Nagasaki, Japan

Department of Preventive Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Department of Occupational Therapy, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan

Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan

Department of Clinical Psychology, School of Psychological Science, Health Sciences University of Hokkaido, Hokkaido, Japan

Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan

Department of Medicine, Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
For all author emails, please log on.

BioPsychoSocial Medicine 2014, 8:10  doi:10.1186/1751-0759-8-10

The electronic version of this article is the complete one and can be found online at:

Received:19 November 2013
Accepted:11 March 2014
Published:21 March 2014
© 2014 Saigo et al.; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.



The visceral sensitivity index (VSI) is a useful self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS). Previous research has shown that worsening GSA in IBS patients is related to the severity of GI symptoms, suggesting that GSA is an important endpoint for intervention. However, there is currently no Japanese version of the VSI. We therefore translated the VSI into Japanese (VSI-J) and verified its reliability and validity.

Material and methods

Participants were 349 university students aged 18 and 19 years and recruited from an academic class. We analyzed data from the VSI-J, Anxiety Sensitivity Index (ASI), Hospital Anxiety and Depression scale (HAD), and Irritable Bowel Syndrome Severity Index (IBS-SI). The internal consistency, stability, and factor structure of the VSI-J and its associations with anxiety, depression and severity measures were investigated.


The factor structure of the VSI-J is unidimensional and similar to that of the original VSI (Cronbach’s α = 0.93). Construct validity was demonstrated by significant correlations with ASI (r = 0.43, p < 0.0001), HAD-ANX (r = 0.19, p = 0.0003), and IBS-SI scores (r = 0.45, p < 0.0001). Furthermore, the VSI-J was a significant predictor of severity scores on the IBS-SI and demonstrated good discriminant (p < 0.0001) and incremental (p < 0.0001) validity.


These findings suggest that the VSI-J is a reliable and valid measure of visceral sensitivity.

Gastrointestinal-specific anxiety; Irritable Bowel Syndrome (IBS); Motility; Psychosomatics; Validation; Visceral Sensitivity Index (VSI)


Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder not associated with organic disease that consists of chronic abdominal discomfort associated with abnormal bowel habits [1,2]. The prevalence of IBS has been reported at approximately 5–11% in industrialized countries [3]. Patients with IBS have been shown to have poor health-related quality of life (QOL) when compared with healthy individuals [4] and often experience a significant financial burden—indeed, their economic impact factor increases from 1.1 to 6.0 when compared with non-IBS individuals[5]. The characteristic pathophysiological features of IBS are dysmotility [6,7], visceral sensitivity[8,9], and psychological disturbances [10,11]. The GI symptoms of IBS may aggravate depression and anxiety and be associated with psychosocial stress; indeed, patients with IBS symptoms improve with recovery from psychological disturbances [12-14]. At least two studies have shown that patients with IBS report a high frequency of comorbid anxiety disorders such as panic disorder, agoraphobia, generalized anxiety disorder, and post-traumatic stress disorder [14,15].
Anxiety symptoms play a major role in the onset of IBS and in the maintenance and aggravation of GI symptoms [15]. Further, in IBS, the maintenance and aggravation of GI symptoms and pain is related to brain function through the emotional motor system (EMS) and responses of the neuroendocrine and autonomic nervous systems [16]. For example, in studies that used colonic barostats, the thalamus, insular cortex, anterior cingulate gyrus, and prefrontal cortex were activated; these activations were associated with abdominal pain and psychological abnormalities such as anxiety and depression [12,17-19]. Patients with IBS show greater activation of the prefrontal cortex and anterior cingulate gyrus than do healthy individuals, and also perceive more abdominal pain [12,16-18]. Patients with IBS also demonstrate enhanced pathological vigilance and selective attention for their GI symptoms [20,21]. Thus, the association of brain function with pathological vigilance and selective attention for GI symptoms suggests a neurophysiological foundation for visceral sensitivity [22-24]. GI symptoms are not only external stressors but also act as internal stressors by causing and aggravating anxiety (gastrointestinal-specific anxiety: GSA) [25]. Excessive activity of the amygdala can activate the insular cortex [26], prefrontal cortex, and the anterior cingulate gyrus, which ultimately may lead to GSA and aggravated GI symptoms [4,27]. Interventions aimed at reducing GSA associated with IBS should therefore contribute to an improvement in the QOL of patients with IBS [27,28].
GSA is defined as “the cognitive, affective, and behavioral response stemming from fear of GI sensations, symptoms, and the context in which these visceral sensations and symptoms occur” (28, p.89). For example, the fear of visceral sensations and GI symptoms is related to situations involving restaurants, parties, or first-time visits to locations where bathroom facilities are unknown or difficult to reach; such experiences may cause particular cognitive or behavioral responses. IBS patients may engage in avoidance behaviors that cause GSA, increase vigilance or attention to visceral sensations, and show excessive reactions to low-level visceral sensation [29]. Labus et al. [27] have developed the Visceral Sensitivity Index (VSI) to assess specific GSA seen in patients with IBS.
The validity and reliability of the VSI have been confirmed in several studies (27 28, 30). In studies with both university students and IBS patients, the VSI has been shown to have a unidimensional factor structure [27,28]. A high level of internal consistency has been demonstrated in a combined group of younger healthy participants, IBS patients (Cronbach’s α ranging from 0.90 to 0.92), and adults with IBS (Cronbach’s α = 0.93) [27,28]. Test-retest reliability estimates showed that, four weeks after testing, the inter-class coefficient was 0.86 [30]. Further, the construct validity has been extensively studied; results for the original VSI show moderate to strong positive correlations with measures of anxiety sensitivity (AS), state anxiety, and severity of GI symptoms [27,28,30]. The original VSI also showed a strong positive correlation with the depressive symptoms of IBS patients, but there was no significant correlation with the depressive symptoms of university students with IBS [28]. In addition, the Norwegian version of the VSI showed no correlation with the depressive symptoms or indicators of food sensitivity of IBS patients [30].
There is currently no Japanese version of the VSI; however, there is a clear need for such an instrument because it could be useful for verifying treatment effects in IBS patients and may therefore be indispensable for the future development of IBS treatments [27]. In the present study, we report our newly developed Japanese version of the VSI and test its validity and reliability. Reliability and validity have been confirmed in a previous analog study of university students [28]. As a large sample was necessary to develop the Japanese version of the VSI, the present study was conducted with a sample of university students, including those with symptoms of IBS. We then tested the following hypotheses.
1. The Japanese version of the VSI will exhibit a unidimensional factor structure.
2. The Japanese version of the VSI will show moderate positive correlations with measures of AS, state anxiety, and the severity of IBS symptoms; furthermore, it will show weak positive correlations with measures of depressive symptoms.
3. The Japanese version of the VSI will predict the severity of IBS symptoms after controlling for AS and state anxiety.



We recruited 875 undergraduate student participants from Nagasaki University in Japan; Figure 1shows the selection process. For the present study, we were interested in younger participants (less than 20 years old). After screening for age, the data of 349 students (male = 207, female = 142, mean age = 19 years) was available for analysis. The participants answered all items on the VSI questionnaire.
Figure 1. Flow chart showing the selection of the participants. Of 875 possible participants, 66 were absent from class, 410 did not respond to the questionnaire, 38 did not fully complete the questionnaire, and 22 were excluded because they were 20 years of age or older. We analyzed the data of the remaining 349 persons who answered all of the items on the questionnaire.

Japanese Version of the Visceral Sensitivity Index (VSI-J)

The VSI was translated into Japanese using a standardized procedure. Two researchers, one a clinical psychologist knowledgeable in psychosomatic medicine, translated the original version. A medical doctor who specializes in psychosomatic medicine then confirmed the consistency of the translated Japanese version. A bilingual researcher (native English speaker) back-translated the Japanese VSI into English. The VSI-J was established after comparing the results of the back translation to the original, and there was agreement among the researchers about the nuances (Tables 1 and 2).
Table 1. Original version of the VSI [27]
Table 2. Japanese version of the VSI
The VSI measures gastrointestinal specific anxiety using 15 questionnaire items, with responses ranging from 1 (strongly agree) to 6 (strongly disagree). The VSI was “reverse scored” according to previously established methods [27], with scores ranging from 0 to 5. Total scores ranged from 0 (no GI-specific anxiety) to 75 (severe GI-specific anxiety).

Rome III diagnostic questionnaire

Rome III criteria are widely used for the diagnosis of IBS. These criteria include recurrent abdominal pain or discomfort (on at least 3 days/month in the last 3 months) associated with two or more of the following: [1] improved by defecation, [2] onset associated with a change in frequency of stool, and [3] onset associated with a change in form (appearance) of stool. The Rome III diagnostic questionnaire has been confirmed as a reliable and valid self-administered questionnaire for the purpose of diagnosing IBS (Drs. Kanazawa & Fukudo, personal communication). The questionnaire determines whether a person is IBS-positive or non-IBS.

The IBS Severity Index (IBS-SI)

In the present study, the IBS-SI was used to assess the severity of GI symptoms [31]. The IBS-SI consists of five items with total scores ranging from 0 to 500. Mild, moderate and severe symptoms of IBS are indicated by scores of 75 to 174, 175 to 299, and 300 or over, respectively[31]. The VSI has shown strong positive correlations with the severity of the GI symptoms of both healthy (non-IBS) individuals and individuals with IBS (IBS-positive) [28]. Therefore, the IBS-SI measure of symptom severity was used to examine the construct validity of the VSI-J.

The Hospital Anxiety and Depression scale (HAD)

The HAD is a 14-item self-administered anxiety and depression scale specifically designed for use in non-psychiatric settings [32]. Seven of the items relate to anxiety (HAD-ANX) and seven to depression (HAD-DEP). Participants rate each item on a scale from 0 to 3. Higher ratings indicate a greater number of symptoms of anxiety or depression. Two scores (one each for the HAD-ANX and the HAD-DEP) are calculated, each ranging from 0 to 21. Scores of 0 to 7 on the respective subscales are considered normal, with 8 to 10 being borderline and scores of 11 to 21 indicating probable clinical cases [32]. Our scoring methods conformed to those of the original version of the scale [32]. Scores on the original VSI were significantly and moderately correlated with scores on the HAD-ANX but showed a weak correlation with HAD-DEP scores [28]. Therefore, the HAD was used to examine the construct validity of the VSI-J.

The Anxiety Sensitivity Index (ASI)

The ASI is a 16-item self-administered questionnaire about anxiety sensitivity designed to assess fear of bodily sensations associated with arousal [33,34]. Items are rated on 5-point Likert scales ranging from 0 (very little) to 4 (very much). Previous research has shown that the original VSI is significantly and strongly correlated with measures of AS among both IBS patients and healthy individuals [28]. AS was related to an understanding of GSA constructed through introspection and resulting in worry, fear, and vigilance [27,28]. Therefore, the ASI was used to examine the construct validity of the VSI-J.


The questionnaire survey was presented in the classroom during an academic session. We explained the research procedures and general purpose, and provided both a written and verbal explanation of the intended use of the data. In addition, we explained that persons who did not consent to participate in the study would be placed at no disadvantage whatsoever. We only analyzed the data of those students who agreed to participate.

Statistical analysis

Analyses were carried out using IBM SPSS Statistics 20.0 (SPSS, Inc., Chicago, IL, USA) Descriptive statistics are presented as means ± standard deviations (SD), along with 95% confidence intervals. We used unpaired t-tests to compare IBS-positive and non-IBS groups. The factor structure of the VSI-J was confirmed by exploratory factor analysis (EFA). The internal consistency reliability of the VSI-J was determined using Cronbach’s α. The construct validity was measured using Pearson’s correlation coefficients between the VSI-J and scores on the ASI, HAD-ANX, HAD-DEP, and IBS-SI. The discriminant validity of the VSI-J was measured using the partial correlation coefficient between the VSI-J and the IBS-SI while controlling for HAD-ANX and ASI scores. Hierarchical multiple regression analyses were conducted to examine the incremental validity of the VSI-J; IBS-SI scores were the dependent variable and the scores on the VSI-J, ASI, and HAD-ANX were independent variables. For all tests, a p-value of .05 (two-tailed) was regarded as the cutoff for statistical significance.


The study protocol was approved by the Ethics Committee of Nagasaki University, which confirmed that the study design was in accordance with the Declaration of Helsinki; all participants provided informed consent.



Table 3 shows the demographic data for the present study participants, and reference data for university students obtained in a previous study [28]. The prevalence of IBS in the study sample was 11%; the overall gender distribution of the sample was 59% male and 41% female. However, within the IBS-positive group, 67% were female and 33% were male. The scores were significantly higher for the IBS-positive group than for the non-IBS group on the VSI-J (total; t = 4.96, p < 0.0001), the ASI (t = 2.86, p = 0.0044), and the IBS-SI (t = 8.59, p < 0.0001). However, there was no significant difference in the total HAD-ANX (t = 1.20, p = 0.2305) and total HAD-DEP (t = 0.26, p = 0.7931) scores.
Table 3. Age, sex, and inventory scores

Factor structure

To examine the factor structure of the VSI-J, we conducted an EFA (using maximum likelihood estimation and promax rotation) without assigning the number of factors (Table 4). There are four criteria for estimating factor structure: [1] initial eigenvalues greater than one, [2] shape of the scree plot, [3] interpretations of factor structure, and [4] factor loadings greater than 0.40. Initial eigenvalues greater than one were observed for two factors (first factor eigenvalue = 8.18, second factor eigenvalue = 1.17). However, the shape of the scree plot suggested a unidimensional factor structure. Accordingly, we then analyzed the factor structure by conducting exploratory analyses and assigning either one or two factors. The results confirmed a unidimensional factor structure. That is, a single factor accounted for 54% of the total variance. This was consistent with findings for the original VSI [27,28].
Table 4. Factor analysis of the Japanese version of the Visceral Sensitivity Index


To examine reliability, we calculated Cronbach’s α for all scale measures. All measures demonstrated high internal consistency and were therefore considered reliable (VSI-J, α = 0.93; ASI, α = 0.88; total HAD, α = 0.73; HAD-ANX, α = 0.66; HAD-DEP, α = 0.50; IBS-SI; α = 0.74).


Construct validity

Table 5 gives Pearson’s correlation coefficients among the VSI-J, ASI, HAD-ANX, HAD-DEP and IBS-SI. Overall, scores on the VSI-J were significantly correlated with scores on the ASI (r = 0.46,p < 0.0001), HAD-ANX (r = 0.19, p = 0.0003), and IBS-SI (r = 0.43, p < 0.0001). However, there was no significant correlation with the HAD-DEP (r = 0.10, p = 0.0511). For the IBS-positive group (n = 39), there was a significant correlation between scores on the VSI-J and scores on the ASI (r = 0.44, p = 0.0048), HAD-ANX (r = 0.32, p = 0.0445), and IBS-SI (r = 0.65, p < 0.0001). However, there was no significant correlation between VSI-J and HAD-DEP scores (r = 0.27, p = 0.0976). For the non-IBS group (n = 310), there was a significant correlation between scores on the VSI-J and scores on the ASI (r = 0.41, p < 0.0001), HAD-ANX (r = 0.16, p = 0.0051), and IBS-SI (r = 0.36, p < 0.0001). However, there was no significant correlation between VSI-J and HAD-DEP scores (r = 0.09, p = 0.1096).
Table 5. Correlation matrices for the construct validation of the Japanese version of the VSI
Table 6. Hierarchical multiple regression analysis with IBS-SI as the dependent variable

Discriminant validity

To examine the discriminant validity of the VSI-J, we calculated the partial correlation coefficient (for the whole sample, N = 349) between the VSI-J and IBS-SI while controlling for scores on the HAD-ANX and ASI. The result was a significant correlation between scores on the VSI-J and the IBS-SI (r = 0.45, p < 0.0001). Furthermore, there was a significant correlation between VSI-J and IBS-SI scores when controlling for only the ASI (r = 0.40, p < 0.0001).

Incremental validity

To examine the ability of the VSI-J to predict GI symptoms, we conducted a hierarchical multiple regression analysis (for the whole sample, N = 349) with the IBS-SI score as the dependent variable and the VSI-J, ASI, and HAD-ANX scores as independent variables (Table 6). For the first step, independent variables were the ASI and HAD-ANX scores; for the second step, the independent variable was the VSI-J score. The adjusted multiple correlation coefficient for the IBS-SI increased significantly from the first to the second step (5.2% to 20.5%). These findings suggest that the VSI-J contributed unique effects to the IBS-SI.


Our hypotheses were mainly supported by the findings of the present study. As expected, the VSI-J exhibited a unidimensional factor structure (Hypothesis 1). Further, VSI-J scores were significantly and moderately correlated with scores on the ASI, HAD-ANX, and IBS-SI (Hypothesis 2); however, there was no significant correlation between the VSI-J scores and those of the HAD-DEP. As anticipated, when we controlled for ASI (anxiety sensitivity) and HAD-ANX (anxiety) scores, scores on the VSI-J predicted IBS-SI (GI symptom severity; Hypothesis 3).
Our study was able to demonstrate that the VSI-J is a sufficiently reliable measure of anxiety about GI symptoms. We demonstrated (using EFA) that the index has a unidimensional factor structure similar to that of the original VSI. Cronbach’s α was similar to that found in previous studies [27,28] with the original VSI (α = 0.93 vs. α = 0.90–0.93, respectively), indicating that the VSI-J also has high levels of internal consistency.
We were also able to verify the construct validity of the VSI-J. Correlational analyses showed that scores on the VSI-J were related to scores on measures of anxiety sensitivity (ASI), anxiety (HAD-ANX), and the severity of symptoms (IBS-SI). This is consistent with previous research with the original VSI [27,28]. We found a significant correlation between measures of anxiety sensitivity and gastrointestinal specific anxiety as measured by the VSI-J, confirming previous studies showing that individuals with high trait anxiety and high anxiety sensitivity are more likely to report feeling anxious about their gastrointestinal symptoms [27,28].
Generally, in IBS, a correlation is seen between depression and anxiety [11]. It has also been reported that as GI symptoms increase in severity, psychological distress also increases [12-14]. A previous study has reported that scores on the VSI and the HAD-DEP are significantly correlated in patients with a clinical diagnosis of IBS, although this correlation was not observed in university students with symptoms of IBS [28]. Given previously reported findings regarding the correlation between depression and anxiety in individuals diagnosed with IBS, we expected to see at least a weak correlation between the VSI-J scores and the scores on the depression measure (HAD-DEP). However, we did not find such a correlation. This may be due to the fact that, of participants in this study, those with IBS symptoms only experienced moderately severe GI symptoms, as measured by the IBS-SI.
Our analyses revealed two findings important for understanding the relationship between anxiety and gastrointestinal symptoms. The results of the partial correlation analysis showed that the VSI-J has discriminant validity, as shown by a significant correlation between the VSI-J and the severity measure (IBS-SI) independent of the effects of anxiety and anxiety sensitivity. Further, the results of the hierarchical multiple regression analysis showed that the VSI-J has incremental validity that uniquely affects the IBS-SI. Therefore, it may be appropriate to assess the symptoms of the IBS patient by treating GSA rather than anxiety or AS. Together, these results suggest two intriguing possibilities. First, AS is highly relevant in cases of respiratory and cardiac sensation [35]. It is therefore possible that the VSI-J measures fear responses to GI symptoms and GI sensations, and that it is possible to predict the severity of IBS-SI scores. Second, hyperactivity in the hypothalamic-pituitary-adrenal axis and prefrontal cortex is associated with increased levels of visceral sensitivity, which may exacerbate GI symptoms [36]. Consequently, it is possible that GSA is associated with symptom severity because of the direct path of the efferent nerve originating in the brain and projecting to the gastrointestinal tract.
It is desirable to conduct additional studies to further confirm the reliability and validity of the VSI-J, and to address the following points.
First, this study included only students attending a university located in a medium-sized city on the island of Kyushu in western Japan. Additionally, the present study was based solely on results from a screening questionnaire; it did not include diagnosis or evaluation of symptom severity by a physician. Therefore, it is not known whether these results can be extended to clinical samples in the general population. It will be important to replicate our findings with a general population of patients diagnosed with IBS. At the same time, however, the prevalence of IBS in this study (14%) was similar to that reported for the general population in Japan [37]. It has also been reported that individuals who had never sought treatment for IBS symptoms had higher state anxiety compared with healthy subjects, which matches the pattern usually seen in IBS patients [37]. Thus, we believe sampling bias was unlikely to have affected the conclusions of the present study.
Additionally, at this time, the total VSI-J score does not distinguish between minor and severe symptoms. In the future, it will be necessary to set guidelines and cut-off points so that the scale may be used in clinical settings.
Finally, attention to the GI symptoms of IBS patients may be related to activity in the anterior cingulate and prefrontal cortex [38]. It is important to further study the relationship between executive functioning and GSA, so that eventually the VSI may be used as a measure of brain-gut interaction.
In terms of clinical application, reductions in visceral sensitivity (as measured by the VSI-J) are anticipated as a possible endpoint for IBS interventions, which incorporate pharmacotherapy, exercise therapy, psychotherapy, and nutritional therapy. In recent years, the VSI has been used in Western countries when implementing cognitive behavioral therapy to reduce anxiety associated with IBS symptoms [29,39,40]. Cognitive behavioral therapy is used with the goal of changing individuals’ evaluations of threat in situations that cause symptom anxiety and to reduce avoidance behavior. This approach has been shown to significantly improve GI symptoms and GSA [29].
In conclusion, the present study examined the reliability and validity of the newly developed VSI-J in a sample of university students. The scale was found to be reliable and valid in a manner consistent with the original VSI. The VSI-J may now be used to better assess the impact of interventions targeting the reduction of GSA in Japanese patients with IBS. Furthermore, the results of this study may aid in efforts to use the VSI to compare psychological aspects of IBS patients across cultures.

Competing interests

The authors report no conflicts of interests.

Authors’ contributions

TS and JT participated in the design of this study, carried out data collection, translated VSI into Japanese, analyzed the data and drafted the manuscript. TH, NN and TT provided the information about the psychological variables. PB carried out back translation into English, and confirmed phrasing nuances with JL and BN. MK, SS and SF evaluated the results of the study and reviewed the manuscript. All authors read and approved the final manuscript.


We would like to express our gratitude to the participants in the present study. This study was supported by the Center for Health and Community Medicine at Nagasaki University and Japan Society for the Promotion of Science KAKENHI Grant Number 24530876.


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Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women

Livia Sanna12Amanda L Stuart2Michael Berk234Julie A Pasco2567Paolo Girardi1and Lana J Williams23*
Unit of Psychiatry, Neurosciences, Mental Health and Sensory Organs Department (NeSMOS), Faculty of Medicine and Psychology, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 281, Geelong 3220, Australia

Department of Psychiatry, The University of Melbourne, Parkville, Australia

Orygen Youth Health Research Centre, Parkville, Australia

Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia

NorthWest Academic Centre, Department of Medicine, The University of Melbourne, Western Health, St Albans, Australia

Department of Medicine, Barwon Health, Geelong, Australia
For all author emails, please log on.
BMC Psychiatry 2013, 13:194  doi:10.1186/1471-244X-13-194

The electronic version of this article is the complete one and can be found online at:

Received:3 June 2013
Accepted:5 June 2013
Published:24 July 2013
© 2013 Sanna et al.; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Psychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population-based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women.


This study examined data collected from 1084 women aged 20-93 yr participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication use where possible and lifestyle factors were documented.


Current psychological symptomatology and mood disorder were associated with increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD-related symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0).


These results indicate that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and treatment, and opens new questions as to the pathways and mechanisms of the association.
Mood disorder; Anxiety disorder; Gastro-oesophageal reflux disease (GORD); Psychological symptoms; Comorbidity; Depression; Gastrointestinal tract; Somatic; Comorbidity


Researchers have repeatedly hypothesized that psychopathology plays a role in reflux pathogenesis and vice versa [1-4]. Gastro-oesophageal reflux disease (GORD) is a common condition due to stomach content flowing back through the lower oesophageal sphincter (LOS), causing bothersome symptomatology characterized by acid regurgitation and heartburn [5]. Prevalence figures vary from 20% of the general population in the United States and the United Kingdom to 5% in China, with Australian studies reporting a prevalence of 9.2% [6,7].
While there is an extensive evidence base suggesting an association between irritable bowel syndrome and psychiatric disorders [8], associations with GORD are relatively poorly researched. GORD and mental well-being have been examined in both gastrointestinal and psychiatric-based clinical care settings with reports of increased likelihood of GORD amongst depressed individuals[9,10] and increased risk of mental illness including depression and anxiety [11], neuroticism [12] and psychological distress [2,3,13] amongst GORD sufferers. Furthermore, frequency and duration of GORD symptoms [2] and a poorer response to treatment including surgical intervention [14] and proton pump inhibitor therapy [4,5], have also been linked to mental well-being. On the other hand, Kamolz and colleagues demonstrated improvements in mental health related quality of life following surgery for GORD [15].
Few population-based studies have investigated the association between GORD-related symptoms and psychopathology [16]. Those that have, report increased odds of reflux in people suffering anxiety and depression, although most utilising self-report symptom scales [1,17,18] and one study using data from medical records [10]. We have previously described increased odds of GORD-related symptoms in men with mood and anxiety disorders in the Geelong Osteoporosis Study (GOS) male cohort, using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP) [19], thus providing a rationale for this study. Encouraged by the need for population-based evidence, we aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women.



The Geelong Osteoporosis Study (GOS) is an age-stratified random population-based sample of women recruited from the Commonwealth of Australia electoral rolls [20]. Participants were recruited from the Barwon Statistical Division between 1994 and 1997, with an additional sample of 20–29 year olds recruited between 2004 and 2008, allowing for continuing investigation of the full adult age range. From a pool of 1127 women who participated in the GOS 10 year follow-up assessment, 32 who did not undergo the psychiatric assessment and 11 who did complete the medical history section were excluded from the current analyses, resulting in a final sample of 1,084 women aged 20-93 yr. Written informed consent was obtained from all participants and the study was approved by the Barwon Health Human Research Ethics Committee.


Data from the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP) [21] was used to determine the age of onset of mood and anxiety disorders. All psychiatric interviews were conducted by trained personnel with qualifications in psychology. Major depressive disorder, bipolar disorder (types I and II), dysthymia, minor depression, mood disorder due to medical condition and substance induced mood disorder were collectively termed mood disorder. Anxiety disorder was defined as the presence of panic disorder, agoraphobia, social phobia, specific phobia, obsessive compulsive disorder, generalised anxiety disorder, anxiety disorder due to a medical condition, substance-induced anxiety disorder or anxiety disorder not otherwise specified.
Psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12)[22], a validated screening tool designed to detect non-psychotic psychiatric disorders in community settings, based on assessment of current state. Binary scoring was used for the 12 items, yielding total scores ranging from 0 to 12, and a cut-off of >3 was applied to define caseness indicative of mental health dysfunction [22,23].
Current medication use was documented. The presence of GORD was self-reported and/or identified by use of medication taken daily for hyperacidity, reflux or ulcers. From a list of common medical conditions, participants were asked, at interview, if they had ever experienced GORD or GORD-related symptoms (lifetime yes/no) and whether the condition had been present during the previous 12 months (current yes/no). Height was measured to the nearest 0.1 cm and body weight to the nearest 0.1 kg. Body mass index (BMI) was calculated as weight/height2 (kg/m2[24]. Alcohol consumption (average grams consumed daily over a 12 month period) was estimated using a validated food frequency questionnaire [25]. Women were classed as active if they participated in light to vigorous activity on a regular basis. Tobacco smoking was classified as current or not. Socio-economic status (SES) was determined using Socio-Economic Index For Areas (SEIFA) scores based on the 2006 Australian Bureau of Statistics Census data [26]. These values were used to derive an Index of Relative Socioeconomic Advantage/Disadvantage (IRSAD), which accounts for high and low income, educational attainment, type of occupation, and other measures of wealth (such as owning a car, or number of bedrooms in a dwelling) and then divided into quintiles.

Statistical analysis

Statistical analyses were performed using Minitab (version 16; Minitab, State College, PA). Values of p < 0.05 were accepted as significant. Differences in characteristics between the groups were compared using chi-square analyses and Mann–Whitney. Binary logistic regression techniques were used to evaluate the relationship between current GORD-related symptoms and current mood/anxiety disorders and psychological symptomatology, and lifetime GORD-related symptoms and lifetime mood/anxiety disorders. Models were adjusted for age, alcohol consumption, BMI, SES, physical activity and smoking status where appropriate and interactions between exposure variables were examined.


Characteristics of the whole group (n = 1084) are shown in Table 1. Of this group, 311 women (28.7%) had a lifetime history of mood disorder [major depressive disorder - 244 (78.5%), dysthymia - 19 (6.1%), minor depression - 31 (10.1%) and bipolar disorder - 23 (7.4%)] and 91 were identified with current mood disorder [major depressive disorder - 48 (52.7%), dysthymia - 19 (20.8%), minor depression - 13 (14.3%) and bipolar disorder - 14 (15.4%)]. A total of 144 participants (13.3%) had a lifetime history of anxiety disorder [generalised anxiety disorder – 10 (6.9%), panic disorder - 59 (41.0%), agoraphobia – 8 (5.6%), social phobia - 23 (16.0%), specific phobia - 36 (25.0%), obsessive compulsive disorder 14 (9.7%), anxiety due to a general medical condition - 2 (1.4%), substance-induced anxiety disorder - 3 (2.1%) and anxiety disorder not otherwise specified - 17 (11.8%)] and 83 were identified with current anxiety [generalised anxiety disorder – 10 (12.0%), panic disorder - 14 (16.9%), agoraphobia – 6 (7.2%), social phobia - 10 (12.0%), specific phobia - 32 (38.6%), obsessive compulsive disorder 6 (7.2%), anxiety due to a general medical condition - 1 (1.2%), substance-induced anxiety disorder - 2 (2.4%) and anxiety disorder not otherwise specified - 12 (14.5%)].
Table 1. Characteristics for the whole group and women with or without current and lifetime GORD
Women with current GORD-related symptoms were older, had a higher BMI, were less likely to be physically active and were more likely to report psychological symptomatology and have a current mood disorder; otherwise the groups were similar (Table 1). Age- (model I) and age- and BMI- adjusted (model II) odds ratios for women with current GORD-related symptoms and mood/anxiety disorders/symptomatology is shown in Table 2. Those with current psychological symptomatology had increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, p = 0.005). Current mood disorders were associated with a 3-fold increased odds of current GORD-related symptoms (adjusted OR 3.0, 95% CI 1.7-5.6, p < 0.001) and current anxiety disorder tended to be associated (adjusted OR 1.8, 95% CI 0.9-3.8, p = 0.10).
Table 2. Age-adjusted (model I) and age- and BMI- adjusted (model II) odds ratios for GORD in women with mood and anxiety disorders and symptomatology
Those with a past history of GORD-related symptoms were older, had a higher BMI, consumed less alcohol and were less likely to be physically active than those with no past history; otherwise the groups were similar (Table 1). A lifetime history of mood disorders was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4, p = 0.03; Table 2). BMI was an effect modifier in the relationship between lifetime anxiety disorders and lifetime GORD-related symptoms. Among obese women, lifetime anxiety disorders were associated with a 4-fold increased odds of lifetime GORD-related symptoms (age-adjusted OR 4.0, 95% CI 1.8-9.0, p = 0.001). There was no association between lifetime anxiety disorders and GORD-related symptoms in non-obese women.


This cross-sectional, population-based study showed a strong association between psychological symptoms, mood disorders and GORD-related symptoms in adult women. The relationship between anxiety disorders and GORD-related symptoms was not as consistent; a positive trend was observed when comparing current anxiety disorders and current GORD-related symptoms, however an association between lifetime anxiety and GORD-related symptoms was only evident among obese women.
Our findings are consistent with previously reported community-based studies demonstrating a relationship between GORD and psychological symptomatology and mood/anxiety disorders[1,10,17,18]. In a Norwegian study (HUNT 2) of over 40,500 participants, those diagnosed with reflux, defined by the presence of either severe symptoms of recurrent heartburn or acid regurgitation, showed an increased likelihood of anxiety and depressive symptoms, as measured by the Hospital Anxiety and Depression Scale, compare to those without reflux [1]. Similarly, another large-scale study [10] demonstrated a 72% increase odds of GORD amongst those with depression in a sample of over 40,000 individuals.
Among women with a lifetime history of anxiety disorder in our sample, only participants affected by obesity were at increased risk of GORD-related symptoms. Findings from Wiklund et al. [4] may help explain these results; BMI was shown to be associated with endoscopy-negative reflux and patients affected by this type of reflux (functional heartburn) were more likely to have anxiety than those with endoscopy-positive acid reflux-symptoms [5]. Thus our positive association between anxiety and self-reported GORD-related symptoms in participants with obesity may be due to them suffering from functional heartburn, rather than GORD. The self-reported diagnosis of GORD-related symptoms in our sample does not allow clarification of this issue.
There are many possible explanations for the association between psychopathology and GORD-related symptoms. As suggested by Kamolz and Velonovich [16], the relationship may be attributed to changes in oesophageal motility and LOS function in response to stressors. In addition, visceral hypersensitivity, which would also explain the frequent overlap between heartburn and irritable bowel syndrome [27] may be caused by psychological factors influencing stimuli processing in the central nervous system (CNS) [28]. Although little is known about the morphological organization of serotonergic neurons in the oesophagus, laboratory and clinical investigations have indicated that serotonin, the main target of both depression and anxiety treatment, plays a role in oesophageal motility [29,30], leading to neurohormonal interaction between the CNS and the gastrointestinal system. On the other hand, it is plausible that the presence of GORD-related symptoms can evoke feelings of depression or anxiety [16] or that there are a subset of patients with co-occurring vulnerability to both mood/anxiety and reflux symptoms [3]. Lastly, there is no evidence, endoscopic or otherwise, that identifies which factors of reflux are significantly related to mental illness [2]. Therefore, future research should focus on factors that mediate the relationship between psychological conditions and GORD, helping to pinpoint the mechanism of action.
The comorbidity between psychological illness and GORD has been shown to be clinically relevant, in that the response to GORD treatment, both pharmacological [5] and surgical [14], is lower amongst patients with psychopathology, and certain antidepressants, especially tricyclics, appear to aggravate GORD symptoms [10]. On the other hand, studies have shown the efficacy of medications used to treat depression and anxiety, such as trazodone [31] and citalopram [32], in improving oesophageal symptoms. Thus, recognising the common comorbidity amongst GORD and mood/anxiety disorders may facilitate recognition, and aid treatment choices. Furthermore, Nunez-Rodriguez [2] reported that GORD was associated with other psychological symptom patterns according to the Symptom CheckList-90-R, suggesting the relationship between psychological factors and reflux may extend beyond mood and anxiety disorders.
Methodological limitations of the current study include the cross-sectional design, which precludes temporal and causal speculation, self-reported GORD diagnosis and the lack of severity evaluation of GORD-related symptoms. Current diagnostic criteria for heartburn, based on endoscopic and pH-metric findings, symptomatology and response to proton pump inhibitor therapy, distinguish between erosive reflux disease, non-erosive reflux disease and functional heartburn. Despite this differentiation, Lee and colleagues [5] found depression not to differentiate in prevalence among the three groups, whilst anxiety tended to be more prevalent in the functional heartburn group. Furthermore, the confounding role of somatisation, frequently associated to depression and anxiety, and previously shown to be related to heartburn symptomatology [2] was not examined. It is also possible that GORD-related symptoms experienced during pregnancy may have been included in the lifetime history. However, as participants were not assessed during pregnancy, it is unlikely that current GORD-symptoms were pregnancy-related. Strengths of the current study include the population-based design and combination of the two types of psychological assessment; a reference standardized semi-structured diagnostic assessment (SCID-I/NP) and a self-report questionnaire (GHQ-12). Most of the literature is based only on self-report questionnaire [4,16], with findings being extrapolated to reflect psychiatric diagnoses, whereas we were able to investigate sub-threshold psychopathology as well as diagnosed psychiatric disorders.


These results provide population-based evidence that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Further research dissecting the pathways and mechanisms of this association is warranted. In the meantime, taking a holistic approach to treatment of these conditions is likely to improve symptoms, treatment choices and prove cost-effective.


BMI: Body mass index; CNS: Central nervous system; CI: Confidence Intervals; GORD: Gastro oesophageal reflux disease; GOS: Geelong Osteoporosis Study; GHQ-12: General Health Questionnaire; IRSAD: Index of relative socioeconomic advantage/disadvantage; IQR: Interquartile range; LOS: Lower oesophageal sphincter; OR: Odds ratio; SEIFA: Socio-economic index for areas; SES: Socio-economic status; SCID-I/NP: Structured clinical interview for DSM-IV-TR research version, non-patient edition; DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision.

Competing interests

Livia Sanna, Amanda L Stuart and Mark A Kotowicz have no conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
Paolo Girardi has in the past three years received research support from Lilly and Janssen, participated in advisory boards for Lilly, Organon, Pfizer, and Schering, and received honoraria from Lilly and Organon.
Julie A Pasco has received speaker fees from Amgen, Eli Lilly and Sanofi-Aventis and funding from the Geelong Region Medical Research Foundation, Barwon Health, Perpetual Trustees, the Dairy Research and Development Corporation, The University of Melbourne, the Ronald Geoffrey Arnott Foundation, ANZ Charitable Trust, the American Society for Bone and Mineral Research, Amgen (Europe) GmBH and the NHMRC.
Michael Berk has received Grant/Research Support from the NIH, Simons Foundation, CRC for Mental Health, Stanley Medical Research Institute, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, Servier and Astra Zeneca. He has been a paid consultant for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck and Pfizer and a paid speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, Sanofi Synthelabo, Solvay and Wyeth.
Lana J Williams has received Grant/Research support from Eli Lilly, Pfizer, The University of Melbourne, Deakin University and the NHMRC.

Authors’ contributions

LS and ALS took part in the conception and design of the study, acquisition of the data, data cleaning and statistical analysis, interpretation of the analysis and took primary responsibility for writing the manuscript. MB, JAP and MAK took part in the conception and design of the study, interpretation of the analysis and critically revised the manuscript. PG took part in the interpretation of data and critically revised the manuscript. LJW took part in the conception and design of the study, interpretation of the analysis, critically revised and supervised the writing of the manuscript. All authors read and approved the final manuscript.


The study was funded by the National Health and Medical Research Council (NHMRC) of Australia. The funding providers played no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or in preparation, review, or approval of the manuscript.
The authors wish to acknowledge the women who participated in the study.


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