INTRODUCTION

Esophageal achalasia (EA) is a rare disease with esophageal dysmotility, characterized by the inability of the lower esophageal sphincter to relax in the setting of absent peristalsis (1). Patients present with symptoms of severe dysphagia, regurgitation, chest pain, and subsequent weight loss.

Living with this chronic, progressive physical disease could be mentally challenging. The health-related and gastrointestinal (GI)-related quality of life has been reported to be significantly diminished for patients with EA (2,3). However, a systematic evaluation of the psychological state has not yet been conducted. Research concerning psychological status in other chronic GI diseases, such as intestinal bowel disease or irritable bowel syndrome, had revealed that patients with intestinal bowel disease or irritable bowel syndrome experienced higher depression and anxiety than healthy controls, especially when disease relapsed (4). In addition, patients with severe psychological distress tended to suffer more aggressive symptoms (5). The corresponding antidepressant or psychological therapy was believed to relieve the symptoms (6), making it a desirable alternative to the existing myotomy treatment of EA.

Therefore, we aim (i) to assess psychological well-being of patients with EA systematically throughout their clinical course and (ii) to determine the relationship between psychological distress and EA symptoms.

METHODS Study design and population

From December 2019 to April 2020, we conducted a single-center, observational, and prospective study involving 70 pairs of age and gender-matched consecutive patients diagnosed with EA and healthy controls in the endoscopy center at our hospital (Figure 1).

Figure 1.:

The filter of patients. A total of 70 consecutive patients diagnosed with EA and 70 healthy control individuals were finally involved in the study. EA, esophageal achalasia; LES, Life Events Scale; PSS-14, Perceived Stress Scale-14; SCL-90R, Symptom Checklist-90 Revised.

The diagnosis of EA was established by typical results of high-resolution manometry, esophagram with a barium swallow, endoscopy, and Eckardt score higher than 4 (7). Healthy controls were included during routine gastroscopy examination without any complaints and positive findings. The Symptom Checklist-90 Revised (SCL-90R), Perceived Stress Scale-14 (PSS-14), and Life Events Scale (LES) in Chinese versions were completed by the 2 groups who spoke Chinese fluently. For patients with EA, per oral endoscopic myotomy (POEM) was scheduled as indicated, and the questionnaires were completed before and 3 months after POEM. A flowchart is shown in Figure 1. Patient recruitment followed scientific and ethical approval from the Ethics Committee of Zhongshan Hospital in accordance with the Declaration of Helsinki. Every patient provided their written consent.

Symptom severity Eckardt score

Eckardt score is used to assess the severity of achalasia symptoms, consisting of 4 significant symptoms (dysphagia, regurgitations, chest pain, and weight loss). 0 to 3 points were assigned according to symptom severity. The total score consisted of the following: grade 0, 0–1 point; grade I, 2–3 points; grade II, 4–6 points; and grade III, more than 6 points (8).

Psychosocial measurements SCL-90R

The severity of psychological distress was assessed on a 5-point scale from 1 to 5 by the SCL-90R that includes 90 items and contains 9 subscales: Somatization, Obsessive-compulsive, Interpersonal sensibility, Depression, Anxiety, Anger hostility, Phobic anxiety, Paranoid ideation, and Psychoticism. Seven additional items explore disturbances in appetite and sleep. Three global indexes of distress can measure distress well, which are the Global Severity Index (GSI), Positive Symptoms Total (PST), and Positive Symptom Distress Index. The GSI is the average of all ratings while the PST is used to report the overall number of positive symptoms, and the Positive Symptom Distress Index indicates the average intensity of positive symptoms.

PSS-14

The PSS-14 is a 14-item questionnaire used as a tool to examine the role of stress in disease (9). Each item is rated on a Likert scale ranging from 0 (never) to 4 (very often). Items 4, 5, 6, 7, 9, 10, 12, and 13 are the positively stated items, points of which should be reversed by the initial rated score. The PSS-14 has a possible range of scores from 0 to 56, and higher scores indicate higher levels of perceived stress.

LES

The LES modified for Chinese covered 48 stressful life events that mainly contain 3 categories: (i) Family/Home, 28 items; (ii) Work/Study, 13 items; and (iii) Social intercourse and others, 7 items. Each item was recorded for 4 questions: (i) the date it happened, measured by never occurs, in 1 month, in 1 year, or long term; (ii) whether it was positive or negative for the target person; (iii) the impact on mental health, measured by a 5-point scale from no impact to very severe impact; and (iv) the duration of the event, measured by a 4-point scale from 3 months, 6 months, ≤1 year, or longer. The intensity of each life event is calculated by the impact multiplied by the duration and then by the number of times it happened. Positive intensity, negative intensity, and total intensity were calculated.

POEM

Patients diagnosed with EA underwent POEM as previously reported (10).

Follow-up

Patients were scheduled to follow up at the center 1 month, 3 months, 6 months, and 1 year after operation and yearly afterward, during which symptom assessment, physical examination, and objective tests including esophagogastroduodenoscopy and barium esophagram were performed. High-resolution manometry was recommended to be performed at least once postoperatively.

If patients visited the hospital with the suspicion of recurrence, overall assessment would be performed as listed above to confirm or rule out recurrence.

In the third month after POEM, the 3 psychological scales were sent to patients with EA by phone to update the psychological status after POEM.

Statistical analysis

Quantitative variables were presented as mean ± SD, N ∼ (µ, σ2), or median (range), and categorical variables were demonstrated as numbers with percentages. The Student t test, paired t test, χ2 test, Fisher exact test, Mann-Whitney test, Kruskal-Wallis test, and Spearman rank correlation test were used in the study, and P < 0.05 was considered statistically significant. Calculations were performed with SPSS statistical software version 26.0 and R version 4.0.2.

RESULTS Cohort characteristics

Ultimately, the study comprised 70 patients with EA and 70 healthy persons. They were matched by sex and age. The average ages of the patients and healthy individuals were 37.54 ± 12.12 and 37.87 ± 12.13 years, respectively (P = 0.875). Female predominance accounted for 48.6% both in the EA and control groups.

The Chicago categorization of achalasia identified 70 people with 5 type I, 63 type II, and 2 type III cases. The mean course and Eckardt score of patients with EA were 4.26 ± 5.11 years and 6.63 ± 2.21, respectively. The Eckardt scores contributed similarly among three subtypes (see Supplementary Table 1, Supplementary Digital Content 1, https://links.lww.com/CTG/A980). All the patients in the EA group underwent POEM after completion of questionnaires. Time interval between completion of the questionnaire and POEM was 10.52 ± 13.74 days. The postoperative Eckardt score for the EA group was significantly lower than the preoperative score (P < 0.001). The clinical data of patients with EA are presented in Table 1.

Table 1. - Clinical data of the patients with EA Patients with EA Female, n (%) 34 (48.6) Age, yr, mean ± SD 37.54 ± 12.12 Time interval, d, mean ± SD 10.52 ± 13.74 Disease course, yr, mean ± SD 4.26 ± 5.11 Chicago classification, n (%)  Type I achalasia 5 (7.1%)  Type II achalasia 63 (90.0%)  Type III achalasia 2 (2.9%) Preoperative Eckardt score, mean ± SD 6.63 ± 2.21  Weight loss 1.54 ± 1.16  Dysphagia 2.60 ± 0.73  Retrosternal pain 0.89 ± 0.73  Regurgitation 1.60 ± 0.86 Postoperative Eckardt score, mean ± SD 2.04 ± 2.07  Weight loss 0.13 ± 0.46  Dysphagia 0.93 ± 0.93  Retrosternal pain 0.40 ± 0.65  Regurgitation 0.58 ± 0.84 Previous treatment, n (%) 9 (12.9) Sigmoid esophagus, n (%) 4 (5.7) Mucosal edema, n (%) 2 (2.9) Other cardiac lesions, n (%) 1 (1.4) Mucosa damage, n (%) 5 (7.1) Submucous fibrosis, n (%) 3 (4.3) Full-thickness myotomy, n (%) 27 (38.6) Myotomy length, cm, mean ± SD 10.57 ± 1.14 Perioperative side effects, n (%) 3 (4.3) Surgery time, min, mean ± SD 57.64 ± 23.67 Postoperative reflux, n (%) 3 (4.3)

EA, esophageal achalasia.

Psychosocial parameters

The psychosocial parameter data are provided in Table 2. As expressed by GSI and PST (Figure 2a and b), the degree of psychological distress was significantly greater in the EA group than the control (P = 0.039 and 0.041, respectively). Four subscales of SCL-90R, including somatization (P < 0.001), anxiety (P = 0.021), anger-hostility (P = 0.009), and others (appetite and sleep, P = 0.010), showed significant difference in the 2 groups. The average scores for the 4 subscales of patients with EA were much higher than that for the healthy control individuals (Figure 2d). The total scores of PSS-14 were similar in the 2 groups (P = 0.501). The positive intensity of LES in patients with EA was lower than the controls (P = 0.011) (Figure 2c).

Table 2. - Psychosocial parameters of the patients with EA and healthy individuals Patients with EA (N = 70) Healthy individuals (N = 70) P value SCL-90R  Total score 144.94 ± 44.73 130.31 ± 37.94 0.039  GSI 1.61 ± 0.50 1.45 ± 0.42 0.039  PST 35.06 ± 22.70 27.03 ± 23.31 0.041  NST 54.94 ± 22.70 62.97 ± 23.31 0.041  PSDI 2.47 ± 0.35 2.43 ± 0.48 0.582  Somatization 1.68 ± 0.54 1.33 ± 0.42 0.000  Obsessive-compulsive 1.80 ± 0.59 1.72 ± 0.66 0.454  Interpersonal sensibility 1.65 ± 0.62 1.51 ± 0.50 0.146  Depression 1.69 ± 0.67 1.56 ± 0.61 0.215  Anxiety 1.59 ± 0.55 1.40 ± 0.43 0.021  Anger-hostility 1.73 ± 0.68 1.47 ± 0.48 0.009  Phobic anxiety 1.27 ± 0.35 1.20 ± 0.33 0.260  Paranoid ideation 1.45 ± 0.56 1.40 ± 0.45 0.542  Psychoticism 1.39 ± 0.53 1.32 ± 0.38 0.384  Others (appetite and sleep) 1.73 ± 0.57 1.49 ± 0.50 0.010 PSS-14  Total score 38.09 ± 6.94 37.20 ± 8.51 0.501 LES  Positive intensity 14.23 ± 23.87 28.63 ± 40.30 0.011  Negative intensity 39.00 ± 73.73 29.17 ± 60.00 0.389  Total intensity 53.23 ± 85.59 57.80 ± 87.26 0.755

Values in bold are statistically significant. The results of the scales (SCL-90R, PSS-14, LES) were presented as means ± SD.

EA, esophageal achalasia; GSI, Global Severity Index; LES, Life Events Scale; NST, Negative Symptoms Total; PSDI, Positive Symptom Distress Index; PSS-14, Perceived Stress Scale-14; PST, Positive Symptoms Total; SCL-90R, Symptom Checklist-90 Revised.

Figure 2.:

Psychosocial parameters of patients with EA and healthy individuals. (a) GSI for SCL-90R; (b) PST for SCL-90R; (c) positive intensity for LES; (d) somatization, anxiety, anger-hostility, and others (appetite and sleep) for SCL-90R. EA, esophageal achalasia; GSI, Global Severity Index; LES, Life Events Scale; PST, Positive Symptoms Total; SCL-90R, Symptom Checklist-90 Revised.

The psychological parameters were comparable between 3 subtypes of achalasia (Table 3). We also compared the psychological profiles by Eckardt score and no significant difference was observed (see Supplementary Table 2, Supplementary Digital Content 1, https://links.lww.com/CTG/A980).

Table 3. - Psychosocial parameters of the patients with EA between subtypes by the Chicago classification Type I achalasia (N = 5) Type II achalasia (N = 63) Type III achalasia (N = 2) P value SCL-90R  Total score 112 (101–263) 132 (90–325) 146.5 (90–203) 0.861  GSI 1.24 (1.12–2.92) 1.47 (1.00–3.61) 1.63 (1.00–2.26) 0.861  PST 15 (8–88) 33 (0–86) 28.5 (0–57) 0.644  NST 75 (2–82) 57 (4–90) 61.5 (33–90) 0.644  PSDI 2.69 (2.07–3.13) 2.41 (0–4.05) 1.49 (0–2.98) 0.454  Somatization 1.42 (1.08–2.75) 1.58 (1.00–2.92) 1.92 (1.00–2.83) 0.935  Obsessive-compulsive 1.4 (1.10–3.00) 1.70 (1.00–3.50) 1.70 (1.00–2.40) 0.778  Interpersonal sensibility 1.22 (1.00–3.56) 1.56 (1.00–4.33) 1.67 (1.00–2.33) 0.850  Depression 1.23 (1.08–2.69) 1.54 (1.00–4.46) 1.77 (1.00–2.54) 0.834  Anxiety 1.20 (1.20–2.80) 1.40 (1.00–3.70) 1.50 (1.00–2.00) 0.749  Anger-hostility 1.50 (1.00–3.00) 1.50 (1.00–4.33) 1.84 (1.00–2.67) 0.975  Phobic anxiety 1.14 (1.00–2.29) 1.14 (1.00–2.29) 1.43 (1.00–1.86) 0.948  Paranoid ideation 1.00 (1.00–3.33) 1.33 (1.00–3.83) 1.09 (1.00–1.17) 0.239  Psychoticism 1.10 (1.00–3.40) 1.20 (1.00–3.90) 1.40 (1.00–1.80) 0.701  Others (appetite and sleep) 1.86 (1.00–2.57) 1.71 (1.00–3.57) 1.72 (1.00–2.43) 0.941 PSS-14  Total score 35 (33–44) 39 (18–53) 40 (34–46) 0.784 LES  Positive intensity 0 (0–11) 2 (0–106) 25 (0–50) 0.561  Negative intensity 0 (0–51) 9 (0–308) 48.5 (0–97) 0.824  Total intensity 0 (0–62) 19 (0–412) 73.5 (0–147) 0.574

Values in bold are statistically significant. The results of the scales (SCL-90R, PSS-14, LES) were presented as median (range).

EA, esophageal achalasia; GSI, Global Severity Index; LES, Life Events Scale; NST, Negative Symptoms Total; PSDI, Positive Symptom Distress Index; PSS-14, Perceived Stress Scale-14; PST, Positive Symptoms Total; SCL-90R, Symptom Checklist-90 Revised.

Correlation of psychological distress with achalasia symptoms

When the relationship between achalasia symptoms and psychometric parameters was analyzed, only the somatization score showed positive correlation with chest pain (r = 0.240, P = 0.045, Table 4).

Table 4. - Correlation of psychological distress with achalasia symptoms Eckardt Score Retrosternal pain Regurgitation Dysphagia Weight loss SCL90  GSI    r −0.053 0.133 −0.033 −0.193 −0.04    P 0.662 0.271 0.788 0.109 0.744  PST    r −0.024 0.121 −0.005 −0.127 −0.038    P 0.846 0.317 0.969 0.294 0.755  Somatization    r 0.007 0.240 −0.057 −0.182 0.018    P 0.957 0.045 0.638 0.131 0.883  Anxiety    r −0.03 0.076 −0.023 −0.174 0.021    P 0.805 0.53 0.852 0.15 0.864  Anger-hostility    r −0.131 0.068 −0.018 −0.257 −0.117    P 0.279 0.577 0.882 0.032 0.334  Others    r −0.054 0.094 −0.051 −0.101 −0.061    P 0.657 0.438 0.674 0.405 0.618 LES  Positive intensity    r 0.036 0.096 0.055 −0.129 0.048    P 0.769 0.43 0.648 0.286 0.695

Values in bold are statistically significant.

GSI, Global Severity Index; LES, Life Events Scale; PST, Positive Symptoms Total; SCL-90R, Symptom Checklist-90 Revised.

Psychosocial parameters after POEM and correlation with recurrence

Seventy patients with EA were all got in touch by phone with the psychological scales subsequently sent to them. Thirty-eight patients failed to finish the scale although they agreed to cooperate with the investigation by phone. For 32 patients who submitted the scales back, psychological status was drastically improved as compared with that before POEM, as given in Table 5. Specifically speaking, the total score (P = 0.009), GSI (P = 0.009), and PST (P = 0.002) of SCL-90R were significantly lower after POEM with higher Negative Symptoms Total scores (P = 0.002). In particular (Figure 3), the degree of somatization (P = 0.029), obsessive-compulsive (P = 0.023), interpersonal sensibility (P = 0.001), anxiety (P = 0.002), anger-hostility (P = 0.007), and paranoid ideation (P = 0.042) accounted for the most difference. Besides, the total score of PSS-14 was drastically diminished (P < 0.0001) as compared with that before POEM. Negative intensity and total intensity of LES remained similar after POEM while positive intensity was significantly higher (P = 0.004).

Table 5. - Psychosocial parameters of the patients with EA before and after POEM Before POEM (N = 32) After POEM (N = 32) P value SCL-90R  Total score 148.59 ± 41.02 129.72 ± 39.63 0.009  GSI 1.65 ± 0.46 1.44 ± 0.44 0.009  PST 40.00 ± 22.83 26.56 ± 22.10 0.002  NST 50.00 ± 22.83 63.44 ± 22.10 0.002  PSDI 2.39 ± 0.28 2.36 ± 0.28 0.785  Somatization 1.70 ± 0.53 1.52 ± 0.47 0.029  Obsessive-compulsive 1.83 ± 0.57 1.57 ± 0.50 0.023  Interpersonal sensibility 1.79 ± 0.57 1.44 ± 0.56 0.001  Depression 1.72 ± 0.54 1.52 ± 0.54 0.067  Anxiety 1.63 ± 0.48 1.37 ± 0.51 0.002  Anger-hostility 1.76 ± 0.69 1.45 ± 0.54 0.007  Phobic anxiety 1.30 ± 0.39 1.21 ± 0.33 0.114  Paranoid ideation 1.49 ± 0.50 1.31 ± 0.46 0.042  Psychoticism 1.43 ± 0.49 1.33 ± 0.42 0.243  Others (appetite and sleep) 1.75 ± 0.48 1.57 ± 0.59 0.083 PSS-14  Total score 38.22 ± 7.50 28.91 ± 6.50 <0.0001 LES  Positive intensity 14.38 ± 25.83 31.69 ± 34.2 0.004  Negative intensity 45.69 ± 81.02 31.41 ± 35.47 0.312  Total intensity 60.06 ± 94.14 63.09 ± 55.88 0.861

Values in bold are statistically significant. The results of the scales (SCL-90R, PSS-14, LES) were presented as means ± SD.

EA, esophageal achalasia; GSI, Global Severity Index; LES, Life Events Scale; NST, Negative Symptoms Total; POEM, per oral endoscopic myotomy; PSDI, Positive Symptom Distress Index; PSS-14, Perceived Stress Scale-14; PST, Positive Symptoms Total; SCL-90R, Symptom Checklist-90 Revised.

Figure 3.:

Psychosocial parameters of the patients with EA before and after POEM. EA, esophageal achalasia; GSI, Global Severity Index; LES, Life Events Scale; POEM, per oral endoscopic myotomy; PSS-14, Perceived Stress Scale-14; PST, Positive Symptoms Total; SCL-90R, Symptom Checklist-90 Revised.

With a median follow-up of 19.2 (range 14.6–40) months, 2 patients had recurrence after 13.6 and 22.1 months, respectively, among the 70 patients with EA. However, no correlation was found between recurrence and psychological distress (see Supplementary Table 3, Supplementary Digital Content 1, https://links.lww.com/CTG/A980).

DISCUSSION

The major findings of our study demonstrated that patients with EA had altered psychological status as compared with controls. Patients with EA presented with higher GSI and PST in SCL-90R and LES than healthy controls. Especially for 4 subscales (somatization, anxiety, anger-hostility, and others) of SCL-90R, the degree of psychological distress was significantly greater in patients with EA.

As far as we know, this is the first study to evaluate psychological status comprehensively in comparison with healthy controls with considerable sample size. Song et al (11) reported a similar level of psychometric profiles for depression, anxiety, and somatization in patients with EA as compared with normal controls. Because there were only 7 patients with EA included in the data, it was plausible that the insignificant difference could result from coincidence. Lossen et al (12) reported a higher incidence of depression within 1 year after diagnosis of achalasia. Taft et al recently validated a self-reported measure named Esophageal Hypervigilance and Anxiety Scale and its short form to evaluate esophageal hypervigilance and anxiety in patients with esophageal diseases, including gastroesophageal reflux disease, achalasia, and so on. It was based on their presumption that cognitive-effective processes, hypervigilance and anxiety in particular, compound neuronal hypersensitivity in the digestive tract and centrally mediated pain processing in the brain (13,14). Our findings also supported the notion that patients with achalasia were more likely to experience somatization and anxiety than healthy controls. Therefore, it is important to consider psychological well-being of these patients, and a brief psychological assessment like the Esophageal Hypervigilance and Anxiety Scale or its short form might be incorporated into the clinical course. We noted that the difference in the present study was not drastic. One explanation might be the disease duration. The patients with EA in this study had, on average, been diagnosed for at least 4 years, whereas increased psychological distress was often observed to be most noticeable around the time of diagnosis and within the first 1–2 years in chronic GI diseases (15). As a result, we advise an early psychological evaluation for achalasia patients' mental health.

In this study, we also made efforts to tell whether disturbed psychological status was associated with symptom severity. The somatization score showed positive correlation with chest pain. It has been illustrated that esophageal hypervigilance and visceral anxiety were contributors to symptom severity among patients evaluated with high-resolution esophageal manometry (16). Similarly, somatization was a psychological stress characterized by a propensity to experience and communicate somatic distress in resp