Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders (FGIDs) and comprises various symptoms that appear in the upper abdomen, including epigastric pain, epigastric bloating, early fullness, fullness, nausea, vomiting, and burping. Particularly, FD is a group of heterogenous symptoms involving various pathophysiologies, and the reported prevalence to date is 5%–15% [1]. In terms of diagnosis, it is defined as a syndrome, in which gastrointestinal symptoms appear repeatedly in the absence of organic abnormalities in endoscopic, radiological, and pathological examinations. Especially, since the diagnosis is based on “symptoms,” the ambiguity of the scope has been pointed out [2].

Since the pathophysiology of FD has not been identified to date, the diagnostic criteria for the group with a relatively uniform pathophysiology have been revised several times. Based on the evidence-based guidelines, the 1988 Rome criteria were enacted and have been amended to Rome IV criteria in 2016. To establish a systematic foundation for the diagnosis and treatment of FD, the Rome III criteria has classified FD into two sub-types, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), depending on the primary symptoms. This was maintained in Rome IV criteria [3].

As the sub-types of FD, PDS, and EPS are assumed to have different pathophysiologies and mechanisms according to different symptoms, there may be differences in the therapeutic approach. Their pathophysiologies have been studied in terms of dysaccommodation, delayed gastric emptying, and visceral hypersensitivity but these studies failed to identify the pathophysiological mechanisms. Therefore, a multifactorial model, which states that emotional, cognitive, and behavioral factors influence in addition to physiological factors, has garnered considerable attention [4]. Consequently, the theory based on brain-gut interaction has been highlighted in recent years, and the Rome IV criteria also underscores the importance of the biopsychosocial model.

According to the brain-gut interaction, environmental stress factors, changes in cognition following changes in the mood, and the descending brain signal generated by the changing moods may cause gastrointestinal symptoms through the 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptors. Thus, several studies have been conducted on the association between FD and psychological symptoms [5]. In the systemic literature review conducted by Esterita et al. [6], patients with FD demonstrated a significantly higher level of depression and anxiety compared to those in the control group, and a lower response to treatment was associated with a higher severity of psychological symptoms. Childhood traumas, such as sexual and physical abuse, have been known to be negatively correlated with the symptoms in patients with FGID including FD [7], whereas social support and resilience are known to have a positive correlation with FD. Lackner et al. [8] argued that those with a higher level of social support exhibited improved gastrointestinal symptoms, such as abdominal discomfort, while a lower level of social support was associated with worsening symptoms.

Quality of life (QoL) refers to the state of physical health, functioning, psychological state and well-being, social interaction, economic and occupational status, or religious or spiritual state as perceived by the individual in their life concerning their goals, expectations, standards, and interests amid the culture and value system to which the individual belongs [9]. Previous reports have stated that the QoL in patients with FGIDs, including FD, is lower in comparison to that of healthy individuals [10]. It is well established that psychosocial factors, such as depression and anxiety, significantly influence the symptoms of FD and the QoL of patients with FD [11,12].

Although psychosocial factors are critical in understanding FD, only a few studies have examined them in association with FD. To the best of our knowledge, no study to date compared the psychosocial characteristics of the two subgroups, EPS and PDS. Therefore, we aim to examine the psychosocial characteristics of patients with FD by classifying them into two subgroups, EPS and PDS, as well as identify the factors that influence the QoL in these patients. We would like to see an overall hypothesis about the relationship between higher depression and anxiety in FD patients (and the differences, if any, between subgroups) and variables such as childhood trauma history, social support, resilience, and QoL.

In this study, we aimed to examine the differences in the psychosocial characteristics of FD by classifying the sub-types into EPS and PDS and identifying the effects of those psychosocial factors on the QoL in patients with FD.

Demographic factors did not show a significant difference between EPS and PDS. Previous studies have reported a higher prevalence of FGIDs in women, which may be interpreted as the differences in genetic, physiological, and biochemical responses, resulting in the corresponding differences in hormones, visceral hypersensitivity, cytokines, and brain functioning [21]. Porcelli et al. [22] reported that patients with FGIDs with high levels of education tend to accurately perceive and express emotions whereas those with low levels of education may exhibit maladaptive disease behavior. Regarding age, the incidences of functional esophageal disorders and dyspepsia decrease with increasing age, while reports are stating that the incidence of irritable bowel syndrome (IBS) also typically decreases with increasing age owing to the changes in pain perception, although some studies have reported an increase in incidence, from 8% for ages of 65 and 74 years to 12% in individuals aged ≥85 years [23-25]. Unfortunately, there have been no reports on the differences in the demographic characteristics of FD, specifically between patients with EPS and PDS. However, in the intervention for FD, it would be important to understand through this study that the effect of a single demographic factor on the sub-symptoms of FD is limited while understanding the psychological characteristics represented by these factors.

In this study, both anxiety and depression were found to be high in patients with DPS and PDS compared to healthy controls. Many existing studies have reported the correlation between FD and depression and anxiety [26-29]. Such correlation can be explained by the fact that the cytokines secreted as a result of low-grade gut inflammation change the function of the central nervous system [30]. In addition, it can also be explained by the fact that the increase in the secretion of corticotropin-releasing hormone caused by anxiety results in FD by promoting eosinophils degranulation and increasing the amount of cytokines, such as tumor necrosis factor-alpha [31]. Specifically, in this study, among the sub-factors of depression, emotional and cognitive depression was higher in EPS compared to PDS. In general, depression is explained by cognitive-affective and somatic dimensions [32]. Cognitive-affective dimension includes negative mood and negative affect whereas the somatic dimension includes fatigue or loss of energy [33]. In this study, the differences in emotional and cognitive depression seem to have been caused by pain acting as the major factor. In the case of IBS, a representative FGID syndrome, repetitive pain is known to be the major cause of damaging functionality in the patient [34]. Emotional depression is important in understanding pain because emotional depression causes an individual to constantly reflect on the physical challenges faced in situations of external stress or internal conflict [35]. Consequently, the individual is more focused on the pain, leading to a persistent experience of pain [36]. Moreover, the catastrophizing effect shown in emotional and cognitive depression magnifies the negative aspects of pain, resulting in feelings of despair and difficulty in coping with pain [37]. In a study conducted on patients with fibromyalgia, the patients who tended to catastrophize showed neural activation in the affective regions as well as the secondary somatosensory cortex of the brain in response to a pain stimulus. This can be interpreted as a demonstration of the correlation between catastrophizing and negative affect [38]. Thus, the difference between EPS and PDS for emotional and depression unlike somatic depression may suggest a correlation with pain typically accompanied in EPS in comparison to PDS. In anxiety, there was no significant difference between PDS and EPS. In the tripartite model for depression and anxiety that includes positive affect (PA), negative affect (NA), and physiological hyperarousal (PH), depression has low PA and high NA whereas anxiety has high NA and high PH. Further, in terms of the psychopathological aspect, depression is a more severe type of psychopathology that is above the level of anxiety [39]. In a study by Lee et al. [40], the impact of anxiety was significant in the comparison of healthy controls and the FGIDs group (odds ratio [OR], 10.21; 95% confidence interval [CI], 2.49–41.76), but when the number of visits to the medical institutions was compared among those with FGIDs, the group that visited medical institutions (exhibiting severe symptoms) showed a high risk of depression (OR, 5.554; 95% CI, 2.06–14.97). As this study included patients who visited medical institutions with symptoms of FD, the effects of anxiety were relatively small and the difference between PDS and EPS may have not been significant because of this issue.

Psychological trauma such as abuse or neglect experienced during childhood affects the expression and worsening of FGID symptoms [41,42]. The known causes include the following points: 1) accompanying or experiencing severe psychological distress and complaints of frequent physical symptoms [43,44], 2) maladaptive coping mechanisms [45], 3) dysfunction in interpersonal relationships in adulthood [46], 4) reduction in the threshold of receiving afferent gastrointestinal signals from the central nerve, and 5) the increase in autonomic nervous system activity and gastrointestinal motility due to hyperarousal [47]. However, in this study, there was no difference in K-CTQ between PDS and EPS. In older adult individuals, assessment of retrospective self-reported childhood trauma can be easily influenced by recall and selection biases [48]. Considering that the subjects of this study were older adults, it is highly likely that the recall bias influenced the data on childhood trauma, which led to under-reporting. Thus, in the psychological approach for FD, it is important to focus on the current psychological symptoms based on past distress and develop suitable intervention strategies.

There was no difference between EPS and PDS in the context of social support. Patients with FGIDs are often overlooked by clinicians without receiving proper support or education on the disease despite the discomfort due to symptoms and functional decline [49]. Social support is defined as the resources or interaction provided by others who can help individuals cope with difficulties [50]. The role of social support can be divided into the following two categories: The first category represents the scenario in which the support helps the individuals concerned to continuously have positive experiences to create stable, socially rewarding roles [51]. Through this, it plays an instrumental role in encouraging the patients to maintain specific health-protective behaviors, such as adhering to medical recommendations, exercising, eating nutritional food, and quitting smoking. The second category represents social support that acts as a buffer or attenuates the effects of stress [52]. Previous studies have reported that when a member of a social network provides individuals with proper support, the individuals demonstrated improved health by responding to stressful life events [53]. Thus, adequate education and support on the disease provided by medical staff in a clinical setting would be particularly important in FD cases.

Resilience is the dynamic process of showing positive adaptive skills by an individual who experienced significant adversity or trauma and represents the ability to respond to stress [54]. Highly resilient, individuals not only show psychological and physical health states but also have the comprehensive ability to appropriately respond to various work and social situations [55]. In long-term FGID cases, patients ultimately experience psychological symptoms, such as depression and anxiety, and the important factor in overcoming these psychological symptoms is resilience [56]. In this study, there was no difference among EPS and PDS cases. However, it was significantly lower when compared to healthy controls. Thus, it is evident that meditation utilizing psychotherapy or mindfulness that can amplify the internal resilience of patients with FD would be effective in the treatment of FD.

QoL is a concept that encompasses overall physical, emotional, and spiritual well-being. While depression, anxiety, or distress are factors that reduce the QoL, social support or resilience are known to be the protective factors of QoL [9]. Patients with FGIDs report a QoL that is significantly lower than that of healthy individuals [10]. In a stepwise regression analysis conducted to identify the factors that affect QoL in patients with FD, significant factors included resilience (β=0.328, p<0.001), depression (β=-0.330, p<0.001), and social support (β=0.244, p<0.001), as they accounted for 46.6% of the total explanatory variance for QoL. Thus, attention is required for various psychosocial and psychological factors, including depression in clinical settings, to improve the symptoms of FD and QoL.

This study had several limitations. First, as a cross-sectional study, this study had a limitation in identifying the causal relationship between each variable. Second, the reliability of the study results was limited owing to the possibility of recall bias and under-reporting inherent in retrospective data collection based on self-reported questionnaires. Third, the effects of regional characteristics and treatment environment could not be ruled out as the population was restricted to patients who visited a university hospital in an arbitrary area. Fourth, there was a lack of collected information from young patients as the mean age of the participants was the late 50s. Fifth, covariate factors were not specified during the analysis. Further explanation is needed on this matter.

Despite these limitations, this study had high reliability and was scientifically designed as it assessed psychological symptoms since a psychiatrist conducted psychiatric interviews with patients who were diagnosed with FD after undergoing a physiological test by a gastroenterologist. Moreover, the effects of psychological factors were greater in patients with EPS than in PDS; such results suggest a theoretical basis for empirical understanding that tricyclic antidepressant that control symptoms by acting on pain pathway is mostly used for EPS in clinical settings, while selective serotonin reuptake inhibitor and psychological interventions, such as psychiatric treatment and cognitive-behavioral therapy, are effective for PDS. Therefore, various psychological approaches suitable for the symptoms of each patient should be incorporated into the treatment of patients with FD in the future.