Gastroenterology
Volume 137, Issue 1 , Pages 23-26, July 2009

New Epidemiologic Evidence on Functional Dyspepsia Subgroups and Their Relationship to Psychosocial Dysfunction

  • Lukas Van Oudenhove

      Affiliations

    • Translational Research Center for Gastrointestinal Diseases (TARGID), Gastroenterology Section, Department of Pathophysiology and Psychiatry Division, Department of Neurosciences, University of Leuven, Leuven, Belgium
    • ,
  • Jan Tack

      Affiliations

    • Translational Research Center for Gastrointestinal Diseases (TARGID), Gastroenterology Section, Department of Pathophysiology, University of Leuven, Leuven, Belgium
    • Corresponding Author InformationReprint requests Address requests for reprints to: Prof Dr Jan Tack, Translational Research Center for Gastrointestinal Diseases (TARGID), University Hospital Gasthuisberg, Onderwijs & Navorsing I, Herestraat 49, B-3000 Leuven, Belgium

published online 01 June 2009.

Article Outline

 

See “Anxiety is associated with uninvestigated and functional dyspepsia (Rome III Criteria) in a Swedish Population-Based study,” Aro P, Talley NJ, Ronkainen J, et al, on page 94.

Functional dyspepsia (FD) is a highly prevalent condition, characterized by symptoms suggested to be of gastroduodenal origin, in the absence of an organic cause that is likely to explain them.1, 2 Most studies used the Rome II criteria, which defined FD as the presence of pain or discomfort in the epigastrium in the absence of underlying organic disease.1 In this approach, discomfort refers to a group of symptoms that includes postprandial fullness, early satiation, epigastric burning, belching, nausea, upper abdominal bloating, and vomiting. More recently, the Rome III committee proposed to consider two distinct syndromes, namely postprandial distress syndrome (PDS or meal-related FD, characterized by unexplained postprandial fullness or early satiation) and epigastric pain syndrome (EPS or meal-unrelated FD, characterized by unexplained epigastric pain or epigastric burning).2 However, this major change in defining FD was based on expert opinion and especially on the post hoc interpretation of pathophysiologic and epidemiologic studies that used the Rome II definition.2, 3, 4, 5 It remains to be established whether prospective empirical studies would in fact support this subdivision.

Since then, conflicting data on the validity of the subdivision between EPS and PDS have been emerging. So far, prospectively collected data are lacking, but a number of studies have interpreted existing datasets according to this new subdivision. A population-based study in Olmsted County found support of the existence of both EPS and PDS-like symptom groupings in the population, with the overlap between both less than expected.6 By contrast, major overlap (26%) between EPS and PDS was found in patients referred for open access endoscopy, and several patients with dyspeptic symptoms were not classifiable.7

In the present issue of Gastroenterology, Aro et al8 present results from a large, population-based study on associations between Rome III FD and, among others, anxiety and depression. Although the study confirms that some overlap between both groups exists, it provides evidence for differential association of PDS or EPS with putative pathophysiologic factors. The authors found anxiety to be a significant and independent predictor of uninvestigated and functional dyspepsia, whereas depression was not. Moreover, anxiety was associated with PDS, but not EPS.

A potential causal link between psychiatric disorders and functional gastrointestinal disorders (FGID); has been a matter of ongoing controversy. Evidence in favor of such a link has increased over the past 10 years, although the direction and mechanisms of this putative relationship remain unclear. Probably the most compelling evidence in favor of an association so far comes from a large meta-analysis study by Henningsen et al,9 confirming a highly significant link between FD and the irritable bowel syndrome (IBS) on the 1 hand, and anxiety as well as depression on the other. Although this study included FGID patient samples varying from population level to tertiary care, it showed that the level of depression levels did not differ between consulters (those with dyspepsia who had seen a physician for their symptoms) and nonconsulters, whereas anxiety levels were slightly higher in consulters. These observations argue against the hypothesis that psychiatric disorders merely influence health care seeking in FGID patients rather than being more directly linked to FGID.

Unfortunately, studies on the relationship between FD and anxiety or depression have yielded divergent results. In one of the initial population-based studies, symptom severity and duration, but not psychological comorbidity, predicted health care seeking in patients with dyspepsia.10 Koloski et al11 found anxiety to be a significant and independent predictor of FGID, whereas depression was only significant in univariate analysis. Anxiety was also significantly and independently associated with health care seeking in the whole FGID cohort, but the model only explained a very small part of the variance. The same Australian group reported that general psychological distress was associated with having persistent gastrointestinal (GI) symptoms and with frequent health care seeking.12 In the United States, Locke et al13 demonstrated that IBS and FD, both as a group and separately, were associated with higher scores on virtually all psychopathological domains of the SCL-90, independently of consulting behavior. In a study of 400 primary care dyspeptic patients undergoing endoscopy, the risk of having “mental distress” (measured by the General Health Questionnaire, mostly identifying anxiety and depression) was 4 times higher in dyspeptic patients compared with the Finnish control population, but no difference was found between organic and functional dyspepsia.14 The same group confirmed this finding in a prospective study. At follow-up, dyspeptic symptoms, but not psychological symptoms, were higher in the FD group and psychological changes at follow-up were related to dyspepsia symptom changes, reaching significance in the organic dyspepsia group only.15 Li et al16 found significantly higher anxiety and depression rates in FD compared with controls and organic disorders, including organic dyspepsia, with depression independently associated with FD. A Swedish study observed a significant bidirectional link between psychiatric disorders and FGID, regardless of consulting behaviour.17 Haug et al18 showed a significant link between anxiety/depression and 4 GI symptoms in a large population cohort from Norway. Castillo et al19 demonstrated an association between community dyspepsia and general severity of psychopathology on the SCL-90. Another, although smaller, body of literature reports on the same relationship in the opposite direction, namely comorbidity of FGID in patients primarily presenting with mood and anxiety disorders. These studies, which are mostly not community based, show fairly consistent associations of FGID comorbidity with psychiatric disorders.20 Several studies reported increased prevalences of IBS in depressed patients compared to nondepressed controls or patients with recurrent depression in remission.21, 22 Increased prevalence of both IBS and FD was found in patients with panic disorder.23, 24

Taken together, several of the studies summarized reported associations of FD, or FGID, with anxiety as well as with depression. The Kalixanda study,8 which recruited subjects from the general population and included endoscopy, adds significantly to the existing body of evidence. In this study population, anxiety rather than depression is associated with both uninvestigated and functional dyspepsia, and the association is only significant for PDS. The strengths of the study are the inclusion of a large, representative, population-based cohort with a high response rate; the fact that a large subsample underwent endoscopy and had a complete medical history, allowing reliable exclusion of organic dyspepsia; and finally, the application (although post hoc using a non-Rome III questionnaire) of the recent Rome III criteria diagnostic criteria. In addition, there are also associations with use of anti-secretory drugs or nonsteroidal antiflogistics (Figure 1).

  • View full-size image.
  • Figure 1. 

    Subject selection and prevalence of dyspepsia and functional dyspepsia (subgroups) according to the Rome III classification in the Kalixanda study. The graph illustrates the selection of subjects for endoscopy and the prevalence of dyspeptic symptoms and of functional dyspepsia subgroups according to the Rome III definitions of PDS and EPS. Associations of PDS and EPS with putative pathophysiologic relevance are shown at the bottom of the figure.

The study and its interpretation also have certain limitations. First, as the authors state correctly, this cross-sectional study only allows conclusions about associations, not about directionality, causality, or timing of the relationships studied. Second, the GI symptoms questionnaire used assesses symptoms during the past three months, while the Hospital Anxiety and Depression Scale (HADS) in its standard version measures psychiatric symptoms over the past week; this different time frame may have influenced the associations. Third, the anxiety and depression scores have been dichotomized. Although this has been done using well-established cutoffs for the HADS, it still results in substantial variability in anxiety and depression scores being lost. There is increasing tendency to regard anxiety and depression as continuous, dimensional rather than purely categorical phenomena.25 It would, therefore, be interesting to test the hypothesis of a putative linear relationship between continuous anxiety and depression scores (including their “subsyndromal ranges”) and the odds of having FD. Fourth, it is unclear how much of variance is explained by the final multiple logistic regression model; it remains unclear also how selection of variables has been exactly performed. Moreover, no univariate associations with dyspepsia status are reported. This may be especially important for the (lack of) association between depression and FD in the logistic regression model, which may at least partly be because of its likely association with anxiety; it is well-established that comorbidity between anxiety and depression is highly prevalent.26

Thus, the association between depression and FD still deserves further clarification. In a tertiary care cohort of FD patients, depression was 1 of the determinants of symptom severity, beside somatization.27 Similarly, the failure of venlafaxine therapy in FD that was recently reported28 does not exclude a role for depression as several factors concerning study design and choice of drug may have contributed to the negative outcome.29 The association of anxiety with FD and with PDS in particular also deserves further studies, because causality remains to be established. Moreover, it has been shown that symptom-specific anxiety may be more strongly linked with IBS status and symptom levels than more general forms of anxiety (as measured in this study by a broad screening tool such as the HADS).30 In support of a potential causal relation, we demonstrated previously that experimentally induced anxiety decreases gastric compliance and accommodation to a meal and increases epigastric symptom scores during a standard nutrient challenge.31 It is conceivable that similar mechanisms may contribute to symptom generation in FD, and this may impact on choices of therapeutic agents in subsets of FD patients. By contrast, in a patient cohort, associations between gastric sensorimotor function seemed to be present in a subset of patients.32 The latter observation illustrates what is probably the most important limitation in unraveling the pathophysiology of FD: Despite the more restrictive Rome III definitions, FD is most likely a heterogeneous condition, where different factors and their interactions contribute to the symptom complex in each individual patient.3, 32

A real breakthrough in this area is likely to come from longitudinal studies, because they may shed light on the relative timing of the onset of psychosocial dysfunction and FD symptoms. Besides anxiety and depression, future pathophysiology studies will need to take into account numerous additional variables, including gastric sensorimotor function, “somatization,” and genetic factors, among others.

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References 

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 Conflicts of interest The authors disclose no conflicts of interest.

PII: S0016-5085(09)00777-X

doi:10.1053/j.gastro.2009.05.012

Refers to article:

  • Editorial Accompanies Article Anxiety Is Associated With Uninvestigated and Functional Dyspepsia (Rome III Criteria) in a Swedish Population-Based Study , 31 March 2009

    Pertti Aro, Nicholas J. Talley, Jukka Ronkainen, Tom Storskrubb, Michael Vieth, Sven–Erik Johansson, Elisabeth Bolling–Sternevald, Lars Agréus
    Gastroenterology July 2009 (Vol. 137, Issue 1, Pages 94-100)

Gastroenterology
Volume 137, Issue 1 , Pages 23-26, July 2009

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