Sleep disturbance and psychological distress are associated with functional dyspepsia based on Rome III criteria

Adult outpatients from the digestive and psychological departments of First Affiliated Hospital of Nanjing Medical University meeting ROME III criteria for FD between July 2015 and May 2016 were recruited for this study. The included patients have undergone an upper endoscopic test to exclude organic digestive diseases that might have explained the observed symptoms. Local adult volunteers without known gastrointestinal or psychological disorders, who underwent gastric endoscopy as regular medical examination, were recruited as healthy controls. All patients and controls underwent detailed history taking. All subjects with the following conditions were excluded: (a) a history of upper gastrointestinal tract surgery, (b) a history of ulcerative disease or malignancy, (c) current treatment with non-steroidal anti-inflammatory drugs (NSAIDs), (d) use of monoamine oxidase inhibitors or selective serotonin reuptake inhibitors, (e) pregnancy for women, (f) pancreatitis or hepatobiliary disorders, and (g) physical or psychological impairments that prevented from completing the questionnaires. Patients with concomitant irritable bowel syndrome (IBS) symptoms but not meeting the ROME III criteria for IBS were not excluded.

FD was defined as the presence of postprandial fullness/early satiation or pain/burning more than once per week, in the last 3 months according to the Rome III criteria. To diagnose FD and evaluate the severity of dyspepsia related symptoms, the original Rome III functional dyspepsia module [1] was translated into Chinese, confirmed by two digestive disease experts, and scrutinized by two native Chinese speakers without medical background to ensure that the text was easily understandable. The severity of major dyspeptic symptoms (postprandial abdominal fullness or discomfort, early satiety, epigastric pain, and epigastric burning) was rated on a 7-point Likert scale (0, absent; 1, hardly any; 2, mild; 3, moderate; 4, moderately severe; 5, severe; 6, very severe).

A Chinese version of the PSQI questionnaire was used to assess the patient’s recent history of sleep quality. The PSQI questionnaire consisted of 19 self-rating items that can be categorized into seven components, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. The score of each component score was rated from 0 to 3. The sum of these seven component scores provided a global PSQI score, which ranged from 0 to 21. Higher scores indicate poorer sleep. The Chinese Version of PSQI was translated and validated by Liu et al. [7]. In that study, the internal consistency Cronbach’s α was 0.84, the split-half reliability was 0.87, and the 2-week test-retest reliability was 0.81.

Psychiatric distress was estimated using the Chinese version of SCL-90R [8]. The SCL-90R is a self-reporting, clinical symptom rating scale consisting of 90 items. Responses indicate symptoms associated with 9 symptom dimensions, which included somatization (distress arising from perceptions of bodily dysfunction), obsessive-compulsive (thoughts, impulses and actions that are experienced as irresistible and unremitting), interpersonal sensitivity (feelings of inferiority or inadequacy), depression, anxiety, hostility (thoughts, feelings and actions that are characteristic of the negative affect state of anger), phobic anxiety (irrational fear of specific situations or persons), paranoid ideation (paranoid behavior as fundamentally a disordered mode of thinking), and psychoticism [9]. Additionally, a global symptom score is calculated. The Chinese-version SCL-90R questionnaire [8] with established reliability and validity is widely used in measuring psychological distress in Chinese clinical practice and research. In a recent study carried out in patients with alopecia areata, the internal consistency Cronbach’s α was 0.98 and split-half coefficient was 0.95 [10]. Demographic data and lifestyle factors (including age, gender, marital status, body mass index (BMI), education level, smoking, and consumption of alcohol were recorded in all patients and controls). Tobacco and alcohol use was divided into never/rare and regular use (more than once a week). Each questionnaire was completed individually and independently by the participant.

Data were assessed with Statistical Package for the Social Sciences (SPSS) for Windows, version 13.0. Measurement data are mean ± standard deviation (SD). Student t test and one way analysis of variance (ANOVA) were used to statistically assess demographic variables such as weight, height, and BMI. Various sleep disorder parameters and psychological factors between FD patients and healthy controls were also assessed by Student t test. The association of total PSQI score and FD symptom severity score was assessed by Spearman correlation analysis. Risk factors for dyspepsia were initially explored by univariate analysis. Those with P < 0.05 were then entered into a multivariate analysis. Independent risk factors for dyspepsia were subsequently determined by backward elimination logistic regression. Data were expressed as odds ratio (OR) with 95% confidence interval (95% CI). P < 0.05 was considered statistically significant.

Of the 263 subjects eligible for inclusion, a total of 224 (85.1%) individuals agreed to participate in the study. However, 109 individuals did not complete the questionnaires because of low education level or desire to withdraw. Therefore, a total of 115 FD outpatients completed questionnaires, yielding a response rate of 43.7%. Meanwhile, 61 healthy controls were enrolled. The mean age of the control population was 41.36 ± 12.32 years; 80.3% of control individuals were female.

Table 1 describes the basic demography of the study population. The mean age of interviewees was 41.72 ± 12.22 years, ranging from 17 to 61 years. A total of 143 (81.3%) adults were female. There were no significant differences between the two groups in terms of age, gender, marital status, regular tobacco use, and regular alcohol intake. FD patients had lower BMI and level of education compared with the control group.

Mean duration of FD symptoms was 52 ± 50 months, and the patients reported that FD symptoms were present 4.1 ± 2.3 days per week. Among the 115 FD participants, 87 (75.7%) had symptoms consistent with EPS (including 61 individuals with pure EPS symptoms) and 54 (47.0%) conformed to PDS (including 28 with pure PDS symptoms); 26 patients (22.6%) reported dyspeptic symptoms compatible with both EPS and PDS.

Average sleep durations in FD patients and healthy controls were 6.24 ± 1.37 and 6.87 ± 1.05 h, respectively (P < 0.05). Occasional sleep problems were common in both FD and control groups; indeed, 67.2 and 58.6% of FD patients and control participants, respectively, reported having sleep abnormality 1 to 3 days a month. Significantly higher PSQI scores were found in FD patients compared with controls (10.49 ± 3.38 vs 6.77 ± 2.77, respectively; P < 0.01). In addition, as shown in Table 2, six parameters, including subjective sleep quality, sleep latency, sleep duration, sleep disturbance, use of sleeping medication, and daytime dysfunction showed remarkably higher scores in FD patients compared with controls.

To further investigate the association between overall sleep score and FD symptom score, we applied a Spearman regression analysis within patients with FD. There was a significant correlation between total PSQI sleep score and overall FD symptom score (r _p  = 0.63, P < 0.01). A total of 61 FD patients had a score above 11, with 5 having values > 15, which reflects severe sleep disturbance in all domains. Moreover, there was a consistent, stepwise increase of FD symptom scores with increasing sleep scores (Fig. 1).

To assess the associations of various psychological factors with FD development, we first compared ten symptomatic dimensions as well as total SCL-90R scores between FD patients and healthy controls. Interestingly, somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, psychoticism, additional items, and total score showed markedly higher levels in the FD group than in controls (Table 3).

To further identify which psychological factors were independent risk factors for FD, a multivariate logistic regression model was employed (Table 4). Hostility (OR = 4.29, 95%CI 1.12–16.47, P < 0.05) and phobic anxiety (OR = 6.41, 95%CI = 1.40–29.43, P < 0.05) were independent risk factors for dyspepsia. However, no significant associations of symptomatic dimension scores with the FD symptom score were found.

Besides hostility and phobic anxiety, lower BMI (OR = 0.75; 95%CI 0.62–0.91; P < 0.05), lower education levels (OR = 0.77; 95%CI 0.67–0.89; P < 0.001), and higher PSQI score (OR = 1.55; 95%CI 1.30–1.84; P < 0.001) were also independent risk factors for FD (Table 4).

To assess the associations of each FD subgroup with psychiatric distress and sleep disorder, subgroup analysis was performed. EPS was independently associated with somatization, hostility and additional symptoms, while PDS was independently associated with hostility. Both subgroups were independently associated with lower BMI, lower education level, and higher PSQI score (Table 5).