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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 41  |  Issue : 1  |  Page : 9-16

Association of gastroesophageal reflux disease with anxiety, depression, and sleep disorders


1 Department of Pharmacology, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India
2 Department of Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India
3 Department of Pharmacy Practice, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India

Date of Submission09-Mar-2020
Date of Decision12-Apr-2020
Date of Acceptance03-Jun-2020
Date of Web Publication25-Jul-2020

Correspondence Address:
Dr. S Shanmugapriya
Department of Pharmacology, PSG Institute of Medical Sciences and Research, Off Avinashi Road, Peelamedu, Coimbatore - 641 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmedsci.jmedsci_51_20

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  Abstract 


Background: Gastroesophageal reflux disease (GERD) is commonly associated with impaired quality of life. Chronic symptoms in this highly prevalent disorder could potentially lead to psychological manifestations such as anxiety, depression, and sleep disorders. Aim: The purpose of the study was to evaluate the magnitude of association of GERD symptoms based on health-related quality of life (GERD-HRQL) with anxiety, depression, and sleep quality using Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI). Methods: This was a cross-sectional study done at a tertiary care hospital in 241 participants. Cases were patients diagnosed with GERD, and the control group was participants who did not have GERD, devoid of all gastrointestinal symptoms according to GERD-HRQL. Data on age, gender, body weight, smoking/alcohol intake, and medication history were obtained from 98 cases and 143 matched control subjects. The three questionnaires, namely, GERD-HRQL, HADS, and PSQI questionnaires were administered by a trained blinded interviewer. Results: There was a statistically significant difference (P < 0.001) in the mean score of cases in the HADS depression scale (7.35 ± 3.65); the HADS anxiety scale (9.33 ± 4.51) and the mean global PSQI sleep score (4.62 ± 1.96) compared to the controls. Using Pearson's correlation, heart burn (P = 0.036), and regurgitation scores (P = 0.026), including the global quality of life score (P = 0.003), correlated significantly with the anxiety score. We found a statistically significant correlation between heart burn and poor sleep (P = 0.012) but not for regurgitation (P = 0.772). Conclusions: This study highlights the increased risk of anxiety, depression, sleep disorder in GERD, and the significant correlation between HRQL, especially heartburn with anxiety and poor sleep quality. This enlightens that specific screening and treatment strategies targeting such psychological manifestations are imperative for overall improved quality of life in GERD patients.

Keywords: Mood disorders, sleep quality, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, gastroesophageal reflux disease-health related quality of life


How to cite this article:
Shanmugapriya S, Saravanan A, Shuruthi S, Dharsini J S, Saravanan T. Association of gastroesophageal reflux disease with anxiety, depression, and sleep disorders. J Med Sci 2021;41:9-16

How to cite this URL:
Shanmugapriya S, Saravanan A, Shuruthi S, Dharsini J S, Saravanan T. Association of gastroesophageal reflux disease with anxiety, depression, and sleep disorders. J Med Sci [serial online] 2021 [cited 2021 Feb 28];41:9-16. Available from: https://www.jmedscindmc.com/text.asp?2021/41/1/9/290728




  Introduction Top


Gastroesophageal reflux disease (GERD) is a chronic disorder characterized by reflux of the stomach contents, which can give rise to symptoms and complications. Typical GERD symptoms affect patients' quality of life and overall work productivity.[1] In addition, it also contributes to enormous health-care costs. It is a highly prevalent disorder, and a recent systematic review showed that the prevalence of GERD is 18.1%–27.8% in North America, 8.8%–25.9% in Europe, 2.5%–7.8% in East Asia, 8.7%–33.1% in the Middle East, 11.6% in Australia, and 23.0% in South America.[2] Although conventionally considered as a disease affecting middle age and the older population, recent studies have shown that there is a significant increase in the proportion of the disease in the younger age group. 3]

Patient's quality of life is increasingly being considered as a medical outcome index in the evaluation of the impact of GERD symptoms on patients' health status. The impact of GERD on quality of life can be evaluated by a detailed symptom analysis which typically includes heartburn, acid regurgitation and epigastric pain in the majority of the patients using GERD health-related quality of life (HRQL) questionnaire.[4]

Studies have shown that chronic conditions like GERD could secondarily result in psychological manifestations of anxiety, depression, and insomnia. Few studies have also demonstrated that anxiety and depression could decrease the threshold for perception of visceral stimuli, thereby exacerbating the risk of developing functional gastrointestinal (GI) disorders, thus elucidating a bidirectional cause and effect relationship.[5],[6],[7] The current research focuses on the interplay between the psychological manifestations of anxiety, depression, altered sleep, and the symptomatology of GERD with the objective to evaluate the magnitude of the correlation between the quality of life and the psychological status of patients.

Literature evidence reveals that there is a paucity of studies evaluating psychosocial impairment due to GERD symptoms in the Indian population. Hence, this study was aimed to evaluate the magnitude of association of GERD symptoms with anxiety, depression and sleep quality by assessing the correlation of the GERD-HRQL scores with that of anxiety, depression and sleep quality using the respective Hospital Anxiety and Depression scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) scale in Indian patients with GERD. In addition, the study was also designed to analyze whether anxiety, depression, and sleep scores were affected by comorbidities in GERD patients.


  Methods Top


This was a hospital-based cross-sectional questionnaire study done at tertiary care teaching hospital after the approval by PSG Institute of Medical Sciences and Research-Institutional Human Ethics Committee (Approval no: 16/435 dated January 10, 2017). Patients attending Gastroenterology and Medicine outpatient department and diagnosed with GERD were included for the study after obtaining written informed consent. GERD was diagnosed based on the presence of the typical clinical presentation along with the endoscopic features of GERD. The control group were subjects who did not have GERD and were devoid of all GI symptoms, according to GERD-HRQL. GERD-HRQL questionnaire, a disease-specific tool, was used to measure the symptomatic outcomes and therapeutic effects in patients with GERD. The scale had 16 items that focused on heartburn symptoms, dysphagia, medication effects, and the patient's present health condition. Each item was scored from 0 to 5, with a higher score indicating a better quality of life. Two scores, namely heartburn score and regurgitation score, were obtained by the summation of the scores for questions 1–6 and 10–15 respectively in addition to the total score derived by summing all the 15 score values. The 16th question was a patient's satisfaction question based on a 3 point scale.

Velanovich et al. had examined the psychometric properties of the GERD-HRQL in GERD patients and reported that the Cronbach's α coefficient for each subscale ranged from 0.89 to 0.94 demonstrating a high test– retest reliability and internal consistency.[4]

The presence of anxiety and depression levels was assessed using the Anxiety and Depression Scale. The HADS, a widely used scale that had been designed for detecting depression and anxiety in out-patient clinic setting, was used to measure symptoms of anxiety and depression and consisted of 14 items, seven items for the anxiety subscale, and seven for the depression subscale. HADS Anxiety (HADS A) focused on the symptoms of generalized anxiety disorder, and HADS depression (HADS D) was focused on anhedonia, the main symptom of depression. Each item was scored on a response-scale with four alternatives ranging between 0 and 3. The overall score value 8 or higher was considered the cutoff value for the existence of anxiety and depression.[8]

The PSQI, an effective instrument was used for measuring the quality and patterns of sleep based on examination of seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the past month. Scoring of responses ranged from 0 to 3, and all the seven components were summed together with scores of 5 or greater indicating poor sleep quality.[9]

The subjects included in this study were >20 years of age, either newly diagnosed or on proton-pump inhibitor (PPI) therapy. Patients who had concomitant diabetes, hypertension, liver, pancreatic, or chronic renal disease were also included in the study. The participants included were either non-smokers or those who were current or ex-smokers with a smoking index <100 and also non-alcoholic. However, patients who had serious comorbidities such as liver failure, renal failure, morbid obesity, patients with heart disease on antiplatelet therapy, osteoporosis patients and those on long-term nonsteroidal anti-inflammatory drugs (NSAIDs) or other chronic medications which cause gastric reflux and those with documented history of psychiatric illnesses including anxiety disorders, depression or bipolar illness and sleep disorders were excluded. Subjects aged <20 years, pregnant and lactating women were also excluded from the study.

A total of 98 cases by consecutive sampling were recruited from January 2018 to May 2018. Data on age, gender, body weight, alcohol intake, smoking, NSAID intake, concomitant GI medications other than PPI, including their daily dose were obtained. Similarly, data were also obtained from 143 control subjects who were matched so that they represented the same proportion of subjects with age, sex, and smoking status as in the case group. The three questionnaires, namely, GERD-HRQL, HADS, PSQI questionnaires, were administered by a trained interviewer blinded to the group to which the participant belongs.

Statistical analysis

All data were entered in excel, and the statistical analyses were performed using SPSS version 24 (IBM Corporation, United states). The mean HADS and PSQI scores of patients and controls were compared using an independent sample t-test to detect statistical significance. Similarly, Student's t-test was also used to analyze if the mean difference in the scores of the patients with and without comorbidities were significant. In addition, the correlation of the GERD-HRQL scores with anxiety, depression, and sleep quality scores in patients with GERD was performed using Pearson's correlation.


  Results Top


We recruited a total of 241 participants after obtaining written informed consent, among which 98 subjects were GERD patients and recruited to the case group, while the remaining 143 participants were the non-GERD control population. A total of 84 cases were on proton-pump inhibitor therapy, accounting for a percentage of 85.71%. The mean age of the cases was 46 years, whereas the mean age in the control group was 50 years. Among the cases, 55.10% were <50 years of age and 44.90% were in the age group of 50 years and above. Also, 67.35% cases were males and the rest were females with male: female ratio approximating 2:1. The analysis revealed that there was no difference in the mean scores between the cases in the age group <50 years and those who were aged 50 years and above. Among the cases, an independent sample t-test demonstrated that the mean score for anxiety was significantly higher in the female population compared to the males among the cases, but no such significant difference was evident for the depression or the sleep score [Table 1].
Table 1: Comparison of scores across age and gender groups using independent sample t-test

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The mean score of the cases in the HADS D scale (7.35 ± 3.65) was significantly higher (P < 0.001) compared to the mean score of the control population (4.60 ± 3.34) using independent sample t-test. Likewise, the mean anxiety score of the cases (9.33 ± 4.51) was greater in comparison to the mean score of the controls (6.35 ± 3.74) using HADS A, and this difference was also statistically significant (P < 0.001). A similar significance in the PSQI sleep score between cases and controls was also obtained using Student's t-test [Table 2] and [Figure 1]. A Chi-square test revealed that the proportion of cases found to have depression (50%); anxiety (66.32%), and sleep disorder (45.91%) were significantly higher compared to the control population [Table 3].
Figure 1: Chart representing mean ± standard deviation of the scores between cases and controls. The error bars represent standard deviation

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Table 2: Comparison of depression, anxiety, and sleep quality scores between cases and controls using independent sample t-test

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Table 3: Comparison of the proportion of cases and control with and without depression, anxiety and sleep disturbances using Chi-square test

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Analysis of the GERD-HRQL scores revealed that among the 98 cases in the study population, 35 patients (35.7%) had symptomatic heartburn, whereas 45 patients (45.9%) were symptomatic for regurgitation. On the satisfaction scale, 66.35% were satisfied with their present condition and 26.50% recorded a neutral response, while 7.15% were found to be dissatisfied with their current clinical status [Figure 2]. A comparative analysis of whether the mean scores vary significantly among the patients with asymptomatic (scores of ≤12 with each individual question not exceeding 2 for questions 1–6 of the GERD-HRQL indicate heartburn elimination) and symptomatic heartburn with scores of >12, it was found that the though the mean depression and anxiety scores were higher in the symptomatic patients, there was no statistical significance between the mean difference in the scores detectable. However, patients with symptomatic heartburn had a statistically significant higher mean score for sleep disturbance (P = 0.034) compared to the asymptomatic group. However, when a similar analysis was performed for the regurgitation, there was no significant mean difference between those with scores >12 and those with lower scores in all the three scales [Table 4].
Figure 2: Chart representing satisfaction score in Gastroesophageal Reflux Disease-Health Related Quality of life Scale

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Table 4: Comparison of depression, anxiety, and sleep quality scores with gastroesophageal reflux disease-health related quality of life scores of the cases

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Comparison of the mean scores of the cases with and without comorbidities, there was no statistical significance in the mean scores obtained for those with and without diabetes, hypertensive and normotensive patients, those with other comorbidities such as liver disease, pancreatic, or chronic renal disease [Table 5].
Table 5: Comparison of depression, anxiety, and sleep quality scores of cases with and without comorbidities

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Analyzing the correlation of heartburn, regurgitation and satisfaction components of the quality of life scores with the depression, anxiety and sleep quality scores, it was found that neither the heartburn nor the regurgitation score correlated with depression score whilst there was a correlation of the patient satisfaction with the depression score. However, both the heartburn and the regurgitation scores correlated with the anxiety score, including the global quality of life score. Interestingly, we found that there was a statistically significant correlation between heartburn and poor sleep, which was not detectable for regurgitation. In addition, it was found that the patients unsatisfied with their present clinical status were more likely to have depression and poor sleep quality rather than anxiety [Table 6] and [Figure 3].
Figure 3: Chart representing the correlation of Gastroesophageal Reflux Disease-Health Related Quality of Life score with depression, anxiety, and sleep quality scores of cases. *Correlation coefficient r value is significant

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Table 6: Correlation between gastroesophageal reflux disease-health related quality of life score with depression, anxiety, and sleep quality scores of cases

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  Discussion Top


A statistically higher mean score for all the three clinical conditions, namely depression, anxiety, and sleep disturbance was demonstrable in the GERD cases compared to the control group indicating a high risk of these psychological manifestations in patients with reflux disease. Conceivably, impairment in quality of life was also elicited in the cases compared to the control population using GERD-HRQL.

Our study is one of the few studies evaluating the interplay between the HRQL changes in GERD with the various psychological manifestations such as anxiety, depression, and sleep manifestations in a South Indian population. Considering the cut off value of 8 for the diagnosis of anxiety and depression using the respective components of the HADS questionnaire, the study has effectively demonstrated that a high probability of anxiety disorder existed in the GERD population with a mean anxiety score of 9.33 ± 3.51 unlike with respect to depression wherein the mean score was marginally below the cut off value. A similar result was also obtained in another study done in 225 patients by Kessing et al.[10] However, our result was in contrast to a previous study in which depression was found to be one of the most prevalent comorbidities in patients with GERD.[11] Our research revealed that a high proportion of cases (71.42%) had comorbidities amongst which concomitance of liver diseases recorded the highest. However, none of the comorbidities were significantly associated with the HADS or the sleep scores.

Although the literature evidence strongly supports the association of sleep disorder manifestations with GERD[7],[12] the mean global PSQI score of cases in our study did not achieve the significant cut-off level of 5 indicative of poor quality sleep despite the mean score being significantly higher than the control population. This could be potentially because a large majority of patients (85.71%) were on treatment with PPI. A systematic review has delineated that a statistically significant improvement in sleep quality occurred after initiation of PPI therapy in GERD patients though it may not be completely successful in normalizing the sleep quality to achieve a global PSQI score that is not statistically different from the control population.[13] The large proportion of cases on PPI therapy precluded a between-group analysis of the depression, anxiety, and sleep scores with the patients not on PPI in our research. Symptomatic relief with PPI therapy can consequentially alleviate the psychological manifestations in GERD though evidences support that persistent symptoms despite PPI treatment is quite common which can impede the improvement in severity of the psychological parameters.

Studies have supported that chronic and mild inflammation in the GI tract due to GERD could result in up-regulation of the central nervous system (CNS) cytokine production which in turn can affect the CNS functions, ultimately resulting in psychiatric manifestations such as depressive and anxiety disorders.[14],[15],[16] Studies in animal models have also demonstrated that chronic peripheral inflammation induces central pro-inflammatory markers like interleukin IL-1β as well as tumor necrosis factor alpha-α;[17] the long term elevation of which significantly correlate with the occurrence of psychological manifestations supporting the hypothesis.[18]

In addition, the symptom complex of GERD enables envisioning the intertwined and bidirectional nature of the relationship between sleep disorders and GERD. GERD results in heartburn, acid reflux, sinusitis or sinus problems, and frequent dry cough necessitating throat-clearing that awakens the patient during sleep. Frequent arousal during sleep activates neuroendocrine systems, including the vagal nerve and triggers bronchoconstriction. Frequent bronchoconstriction narrows the diameter of the respiratory tract and arouses patients from sleep, intensifying sleep disorders.[19],[20],[21] Furthermore, GERD-related micro-aspirations inducing bronchial exudative mucosal reaction also adds to the narrowing in diameter of the respiratory tract, accelerating sleep disorder.[22] The flip side of the coin is that for several reasons, GERD symptoms aggravate during sleep. Anti-reflux mechanisms such as swallowing rate, upper and lower esophageal sphincter pressure, gastric emptying, and the awareness of heartburn have all been found to be depressed during sleep. Also, while recumbent, the force of gravity encourages the flow of gastric content towards the esophagus. Thus, current literature supports the fact that sleep disorder has a dual cause and effect relationship with GERD.[13],[23]

A differential effect of the two predominant symptoms, namely heartburn and regurgitation analyzed using GERD-HRQL, illustrated that heartburn patients had a significantly lower mean PSQI score and a positive correlation with anxiety and poor sleep quality whilst regurgitation only correlated with anxiety score. A similar result has been documented by Lee et al. whose study disclosed that patients with heartburn had more severely impaired daily activity, including sleep interruption compared to those with a predominant regurgitation.[24] Likewise, increased anxiety level has been found to be associated with greater heartburn but not regurgitation.[10] This discrepancy perhaps stems from the differences in physico-pathological mechanism underlying the key clinical presentations of GERD. Reflux episodes inducing regurgitation has been shown to have a higher proximal extent of the liquid component, but less esophageal pH drop, than episodes inducing heartburn.[25]

In the current study, a significant positive correlation between the GERD-HRQL and anxiety was demonstrable but not for depression and sleep derangements. A similar study using a different scale for evaluating depression, anxiety and HRQL was able to prove that there existed a significant correlation of the quality of life with both anxiety and depression.[26] The difference in results could be attributed to the fact that our study was done in a smaller subset of patients with GERD and that most patients were on treatment which also precluded a between-group analysis of untreated patients with those on treatment. Furthermore, the categorization of cases into the erosive and nonerosive disease was not done, and these were our study limitations.

However, the study has clearly brought out the need to understand the increased risk of psychological manifestations including depression, anxiety, and sleep disorders in GERD patients including those on treatment, which necessitates addressal by periodic assessments and redressal by specific planned psychiatric interventions, both pharmacological and behavioral, as a part of the comprehensive treatment plan.


  Conclusions Top


The study highlights that GERD patients constitute a vulnerable population for psychological disturbances such as anxiety, depression, and sleep disorder, which may not be completely eliminated by the treatment of the underlying reflux disease. Hence, periodic evaluation and specific treatment strategies for such manifestations would be beneficial in improving the quality of life in these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: A systematic review. Gut 2014;63:871-80.  Back to cited text no. 2
    
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Regenbogen E, Helkin A, Georgopoulos R, Vasu T, Shroyer AL. Esophageal reflux disease proton pump inhibitor therapy impact on sleep disturbance: A systematic review. Otolaryngol Head Neck Surg 2012;146:524-32.  Back to cited text no. 13
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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