A total of 279 consecutive patients with typical symptoms of heartburn or regurgitation from the Division of Gastroenterology (Union Hospital, Tongji Medical College) and 100 healthy controls selected among the staff of Union Hospital and medical students of Tongji Medical College were enrolled in this study.

All subjects agreed to participate and signed an informed consent form. Subsequently, subjects underwent gastroendoscopy to evaluate for the presence of esophageal mucosal lesions. Based on the results of the gastroendoscopy, the patients were divided into two major groups: RE (including Barrett’s esophagus; males = 71; females = 63) and NERD (males = 66; females = 79). GERD was diagnosed according to the previously proposed Rome III criteria. Patients were excluded for the following reasons: use of prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin; previous treatment with a proton pump inhibitor (patients who were treated with H2-blockers were allowed to participate if the treatment had been discontinued 14 d prior to the initial evaluation); incidence of a peptic stricture or duodenal and/or gastric ulcer visible on upper endoscopy; a history of upper gastrointestinal surgery; comorbidities, such as scleroderma, diabetes mellitus, autonomic or peripheral neuropathy, myopathy, functional bowel disorder or any underlying disease (or medication) that might affect the lower esophageal sphincter pressure or increase the acid clearance time; inability or unwillingness to fully complete all stages of the study; and inability or unwillingness to provide informed consent. This protocol was approved by the Ethics Committee of Tongji Medical College (No. 104).

The Zung Self-Rating Anxiety Scale (ZSAS) was designed by William WK Zung to evaluate the level of anxiety in patients who experience anxiety-related symptoms[9]. The ZSAS contains 20 questions. Each question is scored on a scale of 1-4 (never, some of the time, relatively often, most of the time). Fifteen questions involve the assessment of increasing anxiety levels, and five questions involve decreasing anxiety levels. The ZSAS scores were used to define four categories of anxiety severity: within normal range or no significant psychopathology (20-44 points); presence of mild to moderate anxiety levels (45-59 points); severe anxiety levels (60-74 points); and presence of extreme depression (75-80 points).

Similarly, the Zung Self-Rating Depression Scale (ZSDS) was used to assess the severity of depression in the patients[10]. The ZSDS includes 10 positively worded items and 10 negatively worded items that assess symptoms of depression. Item responses are ranked from 1 to 4, and higher scores correspond to more frequent symptoms. Therefore, for each item, patients give a score according to whether the item has occurred: 1 = never/very rarely/rarely; 2 = once in a while/some of the time/occasionally; 3 = relatively often/very often/often; 4 = most of the time/always/almost always. The ZSDS scores were used to define four categories of depression severity: within normal range or no significant psychopathology (below 40 points); presence of minimal to mild depression (40-47 points); presence of moderate to marked depression (48-55 points); and presence of severe to extreme depression (56 points and above). Total scores on the ZSDS do not correspond with a clinical diagnosis of depression but rather indicate the level of depressive symptoms that may be clinically relevant.

The 36-item Short-Form Health Survey (SF-36) is a commonly used generic questionnaire that includes 36 items clustered into eight dimensions (bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality)[11]. The item scores for each dimension are coded, summed and transformed to a scale from 0 (worst possible health status) to 100 (best possible health status). The SF-36 is well-documented in terms of reliability and validity in all available language versions. Each raw scale score is linearly transformed to t scores. The transformed scores range from 0 to 100; higher scores indicate a better health-related QoL. These physical and mental summary scores served as the dependent variables in our analysis. We performed a separate analysis for each score.

The statistical analyses were performed using SPSS software (SPSS, Version 18; Chicago, IL, United States). For all continuous variables, the mean and standard deviation are presented. One-way analysis of variance was used to compare the parametric quantitative variables, followed by LSD or Tamhane’s T2 test for a post-hoc analysis to further examine the differences among the groups. A χ² test or Fisher’s exact test was used to compare the proportions. All P-values were two-tailed, and the level of significance was defined at 0.05.

A total of 279 patients and 100 healthy controls were included in this study. Patient demographics and clinical characteristics are shown in Table 1. No significant differences were observed with respect to sex or age among the three groups.

A total of 379 people completed the ZSAS questionnaire. The characteristics of the anxiety symptoms according to the ZSAS are detailed in Table 2. The results of the χ² test revealed a significant difference in the constituent ratio of the three groups (P < 0.001). Compared with healthy controls, the constituent ratios of both the NERD group and the RE group presented a significant difference (P < 0.001). The incidence of anxiety was significantly higher in the NERD group than in the RE group (Fisher’s exact test, P = 0.050). As shown in Figure 1, the mean scores of the ZSAS in the NERD group (48.27 ± 10.34) and in the RE group (45.38 ± 10.27) were significantly higher than that of the healthy control group (34.70 ± 8.00) (P < 0.001). Moreover, the mean score of the NERD group was significantly higher than that of the RE group (P = 0.01), suggesting that patients with NERD experienced more severe anxiety than did patients with RE, despite the fact that patients with NERD lacked esophageal erosions.

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Figure 1 Comparison of the Zung self-rating anxiety scale scores in the three groups. RE: Reflux esophagitis; NERD: Non-erosive reflux disease.

A significant difference was observed in the constituent ratios of the three groups (P < 0.001). The SDS scores were significantly higher in patients with NERD (49.65 ± 11.09, P < 0.001) and in patients with RE (46.76 ± 11.83, P < 0.001) compared with those of healthy controls (37.61 ± 8.44) (Figure 2). However, the constituent ratios between patients with NERD and patients with RE were not significantly different (χ² = 6.556, P = 0.085) (Table 3). In addition, the incidence of depression in patients with NERD was higher than that in patients with RE (Fisher’s exact test, P = 0.020).

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Figure 2 Comparison of Zung self-rating depression scale scores in the three groups. RE: Reflux esophagitis; NERD: Non-erosive reflux disease.

The standardized component scales of the SF36 are reported in this text as summary information on QoL shown in Figure 3. Compared with the healthy controls, all of the dimensions had statistically lower scores in the NERD and RE groups (P < 0.05), indicating that the QoL of patients with both NERD and RE was inferior to that of the healthy controls. In the NERD group, the scores of vitality and mental health were statistically lower than those of RE patients, which means that part dimensions of QoL in NERD patients were more decreased than those of RE patients (P < 0.05).

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Figure 3 Comparison of the quality of life in the three groups. ^aP < 0.05, ^bP < 0.01. RE: Reflux esophagitis; NERD: Non-erosive reflux disease.

Correlations between the scores of SAS and SF-36 are shown in Figure 4. All of the dimensions of the SF-36 survey were significantly negatively correlated with the SAS anxiety scores in patients with NERD and RE, which means that QoL of patients with GERD was decreased by anxiety. At the same time, general health and mental health of patients with NERD seemed to decrease more readily due to anxiety symptoms compared with these same dimensions in patients with RE (P < 0.05). The correlation coefficients between the ZSAS scores and the other dimensions of the SF-36 survey, such as physical function, role-physical, role-emotional, and social functioning, were similar in both groups.

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Figure 4 Negative correlations between the Zung self-rating anxiety scale scores and the SF-36 survey. All items of the SF-36 were significantly negatively correlated with the SAS anxiety scores in NERD and RE group (P < 0.05). RE: Reflux esophagitis; NERD: Non-erosive reflux disease.

Correlations between the scores of SDS and SF-36 are shown in Figure 5. All of the dimensions of the SF-36 form were significantly negatively correlated with the SDS scores. As a result of the negative correlation between the ZSAS and the SF-36 form, vitality, mental health and social functioning were significantly correlated with depressive symptoms in both groups. Although bodily pain was significantly correlated with symptoms of depression in both groups, it appeared that patients with RE were more easily troubled by depression. However, the general health dimension was more likely to be lowered by symptoms of depression in patients with NERD (P < 0.05). The correlation coefficients between the ZSDS scores and the other dimensions of the SF-36 form, such as physical function, role-physical, and role-emotional, were similar in both groups.

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Figure 5 Negative correlations between the Zung self-rating depression scale scores and the SF-36 survey. All items of the SF-36 were significantly negatively correlated with the SDS depression scores in NERD and RE group (P < 0.05). RE: Reflux esophagitis; NERD: Non-erosive reflux disease.

Gastroesophageal reflux disease (GERD) has been shown to have a significant negative impact on the quality of life (QoL) of affected patients and may even disrupt their daily activities. The etiology of GERD is multifactorial. Common risk factors for GERD including the absence of a hiatus hernia, a low BMI and the presence of Helicobacter pylori, indicate that this condition is a milder form of disease within the GERD spectrum. The majority of patients with GERD use antacid drugs to control their symptoms. However, the symptoms of GERD are sometimes impossible to control, and these patients tend to have a lower response rate, even to the most potent proton-pump inhibitors (PPIs). According to clinical data, apart from the common risk factors listed above, psychological factors, including anxiety and depression, can also develop in patients with GERD. So, this study investigated the role of anxiety and depression in GERD and their effect on quality of life.

Functional gastrointestinal disease is always concerned with psychological factors. The quality of life of patients is often reduced. As for GERD, PPIs are not always effective. So, it is necessary to explore the course of GERD and its correlation with psychological factors.

Anxiety and depression were concerned with incidence of functional gastrointestinal disease. Our study results indicated the incidence and degree of anxiety in the NERD group were significantly higher than those in the reflux esophagitis (RE) group. As for depression in the NERD group, the results were the same. SF36 was employed to evaluate the quality of life, and the results indicated that QoL of patients with both NERD and RE was inferior to that of the healthy controls. The QoL of NERD and RE patients was significantly correlated with anxiety and depression.

This study may help gastroenterologist to understand the role of psychological factors in GERD. The results may help them to focus on other pathogenic factors for GERD, and try new therapy.

In this study, anxiety and depression scores of patients with NERD and RE were higher than those of healthy controls. The QoL of NERD and RE patients was significantly decreased, especially for NERD ones. The QoL was negatively correlated with anxiety and depression significantly.