Severe Gastro-oesophageal Reflux Symptoms in Relation to Anxiety, Depression and Coping in a Population-Based Study

C. Jansson; H. Nordenstedt; M.-A. Wallander; S. Johansson; R. Johnsen; K. Hveem; J. Lagergren


Aliment Pharmacol Ther. 2007;26(5):683-691. 

In This Article


This study provides evidence of a strong dose-response association between anxiety and depression and an increased risk of reflux symptoms, while no consistent association was observed between covert coping and reflux symptoms.

The population-based design and the high participation rates, acting against selection bias, the large sample size and the ability to adjust for many potential confounders are among the strengths of our study. Weaknesses include the cross-sectional study design, as the analyses were based on prevalent, not incident, reflux cases, although the assessment referred to reflux symptoms experienced during the last year. Thus, the temporal, and hence causal, association between the studied psychiatric factors and reflux symptoms is not possible to establish. Yet, the data regarding anxiety and depression were collected at two points in time. The assessment of reflux symptoms was self-reported and misclassification of the outcome might have been introduced. Moreover, as this population-based study did not include endoscopy data, we could not examine separate associations regarding erosive oesophagitis, non-erosive reflux disease or functional heartburn. However, heartburn and acid regurgitation, the symptoms used for case classification, are regarded as the hallmark symptoms of reflux and the use of questionnaires to assess these symptoms is a well-validated measure of the true occurrence of reflux.[5,36,37] Moreover, in our validation study we found a very high specificity for reflux symptoms in the HUNT questionnaire compared to a more extensive questionnaire.[12] Another weakness is the lack of data regarding current antireflux treatment. However, it is unlikely that study participants having severe enough reflux symptoms to be on regular antireflux treatment would report lack of reflux symptoms during an entire 1-year period. This is supported by our validation study and our previous study using a reflux questionnaire, where we found that a majority of individuals who used antireflux medication still reported severe reflux symptoms.[7,12] There might be a risk of biased selection of functional reflux, but our strict definition of case subjects as only those with severe and specific symptoms of heartburn or acid regurgitation should act against such bias. Exposure misclassification is another potential limitation of our study, but the assessment of self-reported anxiety and depression was based on well-validated measures[28] and the assessment of coping has been employed in other studies.[25] However, chronic anxiety and depression could not be measured in this study as only the study participant's feelings during the last week or month were assessed. Possible differential reporting among cases and controls might have been introduced if reflux cases over reported symptoms of anxiety and depression. However, the study participants were unaware of reflux symptoms as a specific outcome in this large health study, and of our hypotheses regarding reflux symptoms and psychiatric factors. Thus, any potential misclassification is likely to be non-differential, and should not explain our positive findings, but rather dilute the effects as it introduces bias towards the null.[38]

Our finding of positive associations between anxiety and depression and increased risks of reflux symptoms is consistent with some previous cross-sectional population-based studies of smaller sample sizes[2,39,40] and with hospital-based studies.[19,21]Furthermore, in a previous study based on HUNT data where mild and severe reflux symptoms were combined, positive, although weaker, associations between anxiety, depression and reflux symptoms were observed.[23] Our finding of stronger associations is probably due to the strict definition of reflux used in our study. However, in both studies the association between anxiety and reflux symptoms was the strongest.

As the pattern of causality is difficult to assess in this cross-sectional case-control study, there are several potential explanations for a link between psychiatric disorders and reflux symptoms. One explanation is that reflux symptoms may result in anxiety and depression,[19,23,39,40] as a consequence of worry over and being bothered by reflux symptoms over time.[22,23] Furthermore, psychological and psychiatric factors may influence an individual's perception of reflux symptoms,[19] and result in a lower threshold for bodily sensation[21] and alter the way oesophageal stimuli are perceived and reported.[41] Thus, anxiety and depression may exacerbate the sensation of reflux symptoms.[19] Hence, subjects with anxiety and depression may be more likely to report reflux symptoms or seek medical consultation,[23,40] However, in a previous population-based study, the increased prevalence of anxiety and depression was similar between reflux patients who sought medical consultation and those who did not.[40] Finally, psychiatric and psychological factors may truly increase the risk of reflux symptoms.[21,23,40] This is supported by our consistent finding of strong dose-response associations regarding both HUNT 1 and HUNT 2 data, which provides some evidence against reversed causality or co-existing morbidity. Psychologically adverse factors may promote reflux symptoms by decreasing the pressure of the lower oesophageal sphincter,[19] changing the oesophageal motility,[19] increasing the secretion of gastric acid[41] or delaying the clearance of acid from the oesophagus.[41] Moreover, psychiatric disorders may indirectly influence the oesophagus through the effect of different psychiatric medications.[21] A common side-effect of such medications, notably selective serotonin re-uptake inhibitors, is gastrointestinal symptoms[23] and impairment of oesophageal motility.[21] Furthermore, benzodiazepines can lower pain threshold and may alter perception of reflux symptoms. Therefore, a weakness of our study is that no information regarding specific psychiatric medications was available. However, in a previous study, no association between psychiatric medications and reflux symptoms was observed[21] and prior studies indicate that a majority of individuals affected by depression and anxiety do not seek medical care and therefore are untreated.[17] Hence, clinical samples of subjects with depression or anxiety disorders are likely to include more severely ill subjects who use psychiatric medications to a greater extent than subjects with these disorders in population-based samples.[17] Another potential explanation for anxiety and depression increasing the risk of reflux symptoms is a self-abusive lifestyle, as psychiatric disorders may be associated with adverse lifestyle factors such as smoking or obesity.[21] In this study, the associations between anxiety and depression and reflux symptoms were not influenced by such known risk factors for reflux, however. Hence, there seems to be a complex interplay between anxiety and depression and reflux symptoms,[19,40] and the link between psychiatric factors and gastro-oesophageal reflux may be bidirectional.

The findings in our study may be of clinical relevance, as among a subgroup of patients reflux treatment may also improve a subject's psychology.[19] It has been shown that surgical correction for reflux symptoms also improved mental health in reflux patients.[19]

In conclusion, this large population-based study reveals a strong link between anxiety and depression and reflux symptoms, which is not explained by other factors associated with reflux symptoms such as tobacco smoking or obesity.

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