Örebro University School of Medical Sciences Degree Project, 30 ECTS 3th of January 2018

Psychological Profile in Patients with Pathologic Gastroscopic Findings and Functional Dyspepsia:

A Pilot Study Version 2  

Author: Otilia Siversten, Bachelor of Medicine Supervisor: Michiel van Nieuwenhoven, Consultant, Associate Professor in Medicine and

Gastroenterology

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Abstract

Introduction: Quality of life (QoL) has been reported to be lower in patients with functional dyspepsia

(FD). Psychological and psychiatric factors have been shown important, however, on the contribution of

personality factors, little research has been performed.

Aim: To compare symptom burden, features of anxiety/depression and personality traits between patients

with FD and patients with pathologic gastroscopic findings, in order to increase our understanding of FD.

Material and Methods: This pilot study was conducted at Örebro University Hospital, Sweden, in

September to December 2017. Questionnaires on symptoms and QoL, personality traits and features of

anxiety and depression were given to patients undergoing gastroscopy.

Results: The functional group (n=31) experienced nausea, belching, discomfort and pain in the upper

abdomen more frequently, as well as QoL being lower than the organic group (n=60). The functional

group also had significantly elevated levels of depression and anxiety, and significantly higher scores on

neuroticism as well as lower scores on conscientiousness.

Conclusion: The functional group had a higher frequency of dyspeptic symptoms and lower QoL, as well

as higher levels of anxiety, depression and neuroticism. These factors affect health care seeking and

patient outcome. This study can contribute to understanding dyspepsia pathology and to reduce the

burden on patients, as well as society, via a better way of managing these patients in the future. This pilot

study is also an important contribution for designing larger studies yet to come in this field.

Key words: Dyspepsia, Functional Dyspepsia, Depression, Anxiety, Personality Traits, Neuroticism,

Conscientiousness, Quality of life, Gastroscopy, Endoscopy.

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Abbreviations

ASA

BFI

DSM

FD

FGIDs

Acetylsalicylic acid

Big Five Inventory

Diagnostic and Statistical Manual of Mental Disorders

Functional dyspepsia

Functional gastrointestinal disorders

GERD

GI

Gastroesophageal reflux disease

Gastrointestinal

HADS

HCs

Hospital Anxiety and Depression Scale

Healthy controls

NSAID

OG

PHQ-9

PPI

PUD

Non-steroidal anti-inflammatory drugs

Organic group

Patient Health Questionnaire-9

Proton pump inhibitor

Peptic ulcer disease

QoL Quality of life

SERT protein

SSRI

SF-NDI

TCAs

Serotonin plasma membrane transport protein

Selective serotonin reuptake inhibitor

Short Form Nepean Dyspepsia Index

Tricyclic antidepressants

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Introduction Dyspepsia is defined as symptoms originating from the upper abdomen, such as pain/discomfort, a

burning sensation, postprandial fullness or early satiety [1]. Dyspepsia is common and the incidence in

Sweden has been observed being 15.3 per 1000 and the prevalence 25% [2–9]. It can have organic causes,

such as esophagitis or peptic ulcer, or the cause can be functional, which means that standard

investigations cannot identify an organic cause [1–5,8–15]. The prevalence of functional dyspepsia (FD)

is approximately 5-25% [6,7,9,10,16–18].

The aetiology of FD and other functional gastrointestinal disorders (FGIDs) such as Irritable

Bowel Syndrome comprises disturbances in the brain-gut-axis [4,11]. This represents a bidirectional

communication between the brain and the enteric nervous system [4]. Studies on brain function in FD

observed differences mainly around the limbic system and homeostatic afferent processing network,

showing correlations with dyspeptic symptoms and quality of life (QoL) [19–23]. On the gut level,

studies on FD have shown a few microscopical changes, such as neural aberrations [24].

Because of the brain-gut-axis, underlying mood- and anxiety disorders can affect visceral

perception from the gastrointestinal (GI) tract, as well as GI symptoms can affect mood and behaviour

[11]. Psychological factors are therefore considered important regarding symptom severity, i.e. stress

worsens symptoms in FD patients and 46% of subjects with FD were reported to be treated for

psychological or psychiatric disorders [3,4,7]. In longitudinal studies, anxiety and depression has been

shown to be higher in FD-patients, but is also associated with the development of FD [16,18]. However,

little research has been performed to investigate the relationship between personality traits and dyspepsia,

but one study by Filipović et al revealed higher levels of neuroticism among FD-patients in comparison to

patients with peptic ulcer disease (PUD) and healthy controls (HCs) [25].  

FD is often recurrent and pharmacotherapy is ineffective [1–3,9,10,19]. It is associated with

work absenteeism, higher rates of unemployment and functional impairment [15,26,27]. QoL has also

been shown to be lower in persons suffering from dyspepsia, FD in particular. Disease duration is not

related to symptoms, QoL, or anxiety/depression [19,28]. Lower QoL, worries for illness and other

psychological factors, as well as psychiatric illness are factors that affect health care seeking [4,9,12]. FD

implies a high burden on health care resources [26]. In Sweden, costs related to dyspepsia have been

calculated to be 4 billions Swedish crowns/year [4].

Aim The aim of this study is to compare symptom burden, features of anxiety/depression and personality traits

between FD patients and patients with pathological findings on gastroscopy, in order to increase our

understanding of FD. This may lead to a better treatment of FD patients.

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Material and Methods Study design: This pilot study was conducted at the Department of Gastroenterology at the Örebro

University Hospital, Sweden. Data were collected from September to December 2017. Standardized and

validated questionnaires, a medication record form and an informational letter with inquiry of

participation were sent to patients who were planned for a gastroscopy, as well as handed out at the

endoscopy registration office. Exclusion criteria comprised: not filling out the forms correctly, previous

surgery affecting the stomach, adenomatous polyposis, pregnancy or a symptom free patient without

pathological findings (i.e. investigation of anemia). Endoscopic outcomes were screened for gastroscopic

findings. Sex, age and current use of medications were recorded as well. Based on gastroscopy findings,

patients were divided into two groups; 1: the Organic Group (OG) if they had pathologic findings, or 2:

the FD group if no pathology could be found with gastroscopy.

Questionnaires: The Short Form Nepean Dyspepsia Index (SF-NDI) is a validated dyspepsia-specific

symptom- and QoL instrument [13]. It consists of a self-reported Symptom Checklist, covering 15

symptoms over the past 2 weeks, as well as 10 items in 5 subscales of QoL; tension, interference of daily

activities, disruption to regular eating/drinking, knowledge/control over disease symptoms and

interference with work/study. The answers are rated on a Likert scale, with higher scores indicating more

impact.

The 14-item Hospital Anxiety and Depression Scale (HADS) is a validated and widely used

self-report questionnaire, investigating states and severity of anxiety and depression during the last week

[29]. There are 7 questions in each subscale (anxiety and depression), with the possibility of scoring 0-21

points on each of them. In comparison to other psychological measures, HADS does not include questions

that can be signs of physical illness (i.e dizziness or headache), which makes it suitable in this setting

[16,29]. In this study, a cut-off score of 11 or more was used to denote elevated levels of anxiety [29].

The Patient Health Questionnaire-9 (PHQ-9) is a reliable and validated, widely used, self-

administered instrument of 9 items that evaluates depression severity [30]. It comprises how often the

individual suffered from depressive symptoms in the prior 2 weeks, including information on impairment

of normal life due to symptom manifestation, with respect to the Diagnostic and Statistical Manual of

Mental Disorders (DSM) IV criteria for depression disorders. Scoring can range from 0 to 27, where a

score of 5-9 represents mild depression, 10-14 moderate, 15-19 moderately severe, and 20 or more severe

depression [30].

The Big Five Inventory (BFI) is a self-report instrument investigating personality traits [31].

It consists of 44 items covering the five dimensions of personality (extraversion, agreeableness,

conscientiousness, neuroticism and openness), where answers are rated on a Likert scale from 1 to 5 [31].

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Gastroscopy: Gastroscopy was performed by an experienced endoscopist using a Pentax gastroscope. The

endoscopists were not aware of questionnaire results. If biopsies were taken, those were incorporated in

the assessment. In some cases, however, the PAD did not arrive in time so that we could not consider

them. In the OG, endoscopic findings were classified into: gastritis, esophagitis, portal hypertension,

hiatal hernia, ulcus ventriculi, ulcus duodeni, stomach cancer, duodenal cancer, achalasia, duodenitis,

peptic stenosis/stricture, Barrett changes, duodenal polyps, villous atrophy or intestinal bleeding.

Statistical analysis: The data were processed using Microsoft Excelâ and IBM SPSS Statistics for

Windows, version 23. Descriptive statistics were used, and since Kolmogorov-Smirnov test showed that

the data were not normally distributed, the non-parametric Mann-Whitney test was used to compare the

differences between the two groups. A p-value of <0.05 was considered significant.

Ethical considerations: According to the Helsinki declaration [32], all information was solely handled by

the research group and data were presented anonymously. Written informed consent was obtained in most

cases, in others we referred to quality examination.

Results In total, 91 patients were included in the study; 31 FD-patients (females 61.3%) and 60 patients in the OG

(females 60.0%). Median age in the FD group was 44 (range 18-88), and 62 (range 25-86) in the OG,

with the difference being statistically significant (p=0.005). The most common diagnosis in the OG was

hiatal hernia (43.3%), followed by gastritis (38.3%), esophagitis (23.3%) and ulcus ventriculi (13.3%),

see Figure 1. Use of medications in both groups are displayed in table 1.

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Figure 1. Pathological findings on gastroscopy in the OG (in percent). Other include intestinal bleeding,

cancer in ventricle or duodenum, Barrett changes, esophageal stricture/Schatzki ring, duodenal polyp and

achalasia. OG, organic group.

Table 1. Use of medications in the FD group and OG.

Antacids

PPI

NSAID

ASA

Antidepres-

sants

Anxiolytics

None of

the

previous

FD

n=31

2

(6.5%)

13

(41.9%)

2

(6.5%)

6

(19.4%)

2

(6.5%)

3

(9.7%)

11

(35.5%)

OG

n=60

3

(5.0%)

21

(35.0%)

6

(10.0%)

8

(13.3%)

8

(13.3%)

2

(3.3%)

21

(35.0%)

PPI, protonpumpinhibitor; NSAID, non-steroidal anti-inflammatory drugs; ASA, acetylsalicylic acid; FD, functional

dyspepsia; OG, organic group.

Symptoms that differed significantly were frequency of nausea (p=0.020), belching (p=0.038), discomfort

(p=0.032) and pain (p=0.031) in the upper abdomen; the FD-group experienced these symptoms more

frequently. Regarding QoL, the subscales of tension (p=0.015), knowledge/control over disease

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Perc

enta

ge

Pathological findings on gastroscopy

Pathological Findings on Gastroscopy in the Organic group

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symptoms (p=0.032), interference of daily activities (p=0.002) and work/studies (p=0.006), as well as the

subscale mean (p=0.009) were higher in the FD group.

The distribution of depression severity is displayed in table 2. The median scores on

symptoms as well as impairment caused by symptoms was higher on PHQ-9 in the FD group, and this

was statistically significant (p=0.033 and p=0.002, respectively). Elevated levels of depression on HADS

were seen in 13.8% in the FD group and 3.4% in the OG, the median score was significantly higher in the

FD group (p=0.024). Elevated levels of anxiety were seen in 37.9% in the FD group and 15.8% in the

OG. Median score on anxiety was significantly higher in the FD group (p=0.006).

Table 2. Severity of depression across the FD group and OG according to the PHQ-9 results.

No

depression

Mild Moderate Moderately

severe

Severe

FD

n=29

7

(24.1%)

10

(34.5%)

7

(24.2%)

3

(10.3%)

2

(6.9%)

OG

n=53

23

(43.3%)

17

(32.1%)

9

(17.0%)

4

(7.5%)

0

(0%) FD, functional dyspepsia; OG, organic group.

FD patients had significantly higher scores on neuroticism (p=0.021) and lower scores on

conscientiousness (p=0.018). In the FD group, 70.4% had scores above the 50th percentile for neuroticism,

compared to 49.1% in the organic group. The differences for scores on extraversion, agreeableness and

openness were not statistically significant.

Discussion Our patients characteristics are in line with similar studies, showing women having a higher prevalence of

dyspepsia and FD, as well as FD being more common in younger adults compared to organic dyspepsia

[3–6,9,13,15,24,26,27,33,34]. Mean age in other studies was approximately 36-56 years in dyspepsia in

general, 65 years in organic dyspepsia and 40-43 years in FD patients [13,15,24,26,27,33–35]. In our

population, the age differences can also be attributed to the fact that gastroscopy is offered more liberally

to older patients because of the higher risk for organic pathology, according to current guidelines [36].

Dyspepsia was shown to have an organic cause in approximately 15-25% of gastroscopies

in Sweden, and in studies from other countries this number has varied from 22 to 43% [9,13–15,35]. In

our study, 66% had pathological findings on gastroscopy. This high number is probably because of the

fact that we, in contrast to other studies, regarded hiatal hernia (our most prevalent finding) as organic

pathology because this can contribute to dyspeptic symptoms. Since the organic group did not entirely

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consist of patients with dyspeptic symptoms, but also other diseases that required a gastroscopy, previous

numbers may not be entirely translatable to our results.

The OG had demonstrated anxiety- and depression levels which were comparable to the

general population [37,38], and the increase in FD patients was significant. Previous studies have

demonstrated varied associations between dyspepsia and anxiety/depression. Some have not shown an

association between lifestyle and psychosocial factors and dyspepsia, (with the exception of smoking

being a risk factor for ulcers [1,3]). However, most studies demonstrated higher depression- and anxiety

scores in FD-patients, not only compared to HCs but also to organic diseases such as PUD [19–

23,25,27,28,39,40]. Dyspepsia symptoms were positively correlated with depression scores and

associated with anxiety and sleep disorder [12,34].

The SF-NDI demonstrated FD patients to have not only more frequent dyspeptic symptoms,

but also a lower QoL than the OG. Several studies showed that FD-patients have a lower QoL compared

to HCs and organic dyspepsia [13,19,20,22,27]. Shetty et al showed a lower self-rated health in the

domains of pain, usual activities and anxiety/depression in FD [15]. Filipović et al showed that FD-

patients had more problems with emotional distress but not with psychosocial functioning or vitality,

compared to HCs and PUD patients [25]. Ebling et al reported a dependence between dyspeptic

symptoms and the feeling of tension and pain interfering with normal activities, as well as with the

feeling of hopelessness, miserableness and being suicidal [7].

All of the above-mentioned factors are likely to be complexly intertwined. For example,

Nan et al showed that dyspeptic symptom scores were correlated to scores of QoL, anxiety and depression

[19,21], and Dibaise et al reported that FD symptom severity was negatively affecting QoL, including a

significant influence of psychosocial variables (such as depression) on this relationship [12].

We found that FD-patients had significantly higher scores on neuroticism while scores on

agreeableness and extraversion did not differ, similar to previous research [25]. This previous study also

found neuroticism to have mutual concordance with anxiety [25]. Interestingly, conscientiousness was

lower in FD-patients in our study. Since we did not adjust for age, this might be a confounder that needs

to be investigated further.

Serotonin (5-HT) is involved in the regulation of mood and psychological states, as well as

in the sensorimotor function of the GI tract [39]. The serotonin plasma membrane transport protein

(SERT protein) is located on the presynaptic membrane and terminates the serotonergic

neurotransmission by the process of reuptake of 5-HT. Tominaga et al showed an increased density of

SERT in the midbrain and thalamus in FD-patients compared to HCs, and this showed a positive

correlation with GI symptom scoring [39]. The SERT-density in hippocampus did also correlate to GI

symptom- and anxiety scoring in all subjects, and there was a tendency towards significance between

SERT-density in the thalamus and depression scores [39]. This might be a part of visceral sensory/pain

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processing, and Tominaga et al suggest a relation between central SERT disorders and both dyspeptic-

and psychological symptoms in FD-patients, and discuss that anxiety can amplify pain [39].

In this respect, it is interesting that the selective serotonin reuptake inhibitor (SSRI)

escitalopram has no effect on FD symptoms [1], which is remarkable because the mechanism of actions

of SSRIs’ is to block the effect of SERT. In contrast, tricyclic antidepressants (TCAs) also block SERT,

as well as the noradrenalin transporter (NET), which results in an elevation of the synaptic concentrations

of these neurotransmitters, and therefore an enhancement of neurotransmission. TCAs have been shown

to have significant effects on both pain and motor activity in the GI-tract, and they are used to treat FD

[1,2,4,9]. Psycho- and hypnotherapy has also shown positive effects on FD [4].

It might not be surprising that FD-patients have lower QoL and more symptoms of anxiety

and depression, since these patients are more often not responding to treatment, have protracting and

recurrent symptoms and work absenteeism, which of course can lead to worrying, anxiousness or feeling

hopelessness, as well as an increased vigilance to symptoms, affecting QoL. It may be suggested that

neuroticism contributes to these tendencies. Neuroticism may lead to more care-seeking behaviour, and

dissatisfaction regarding the information that is provided to the patient. Worrying may lead to stress,

which can lead to an increase in symptom burden.

The Rome criteria for FD comprise criteria for symptom duration, which we did not

consider in this study. In Örebro, patients can book a gastroscopy themselves, hence the duration of

symptoms plays a less important role in this clinical setting. However, Dibaise et al showed patients that

FD patients not fulfilling the duration criterion had equal or results closer to normal than FD-patients

fulfilling this, both regarding QoL, GI symptoms and psychological ones [12]. In Dibaises’ study, patient

characteristics such as sex, age and sociodemographics were similar between those two groups as well

[12].

Because most patients are candidate for a patient-booked gastroscopy, we acknowledge that

this study includes potential confounders, such as comorbidities, sociodemographics etc., but we decided

not to adjust for such factors in this pilot study. However, studies have shown that sociodemographic

factors are not significantly associated with FD, and no differences in sociodemographic factors were

seen between FD patients and patients who underwent a gastroscopy for iron deficiency and suspected

celiac disease [17,41]. Furthermore, because of the small study sample, further statistics (i.e. subanalysis)

were not applicable. We did not perform a Bonferroni correction, but are aware of the fact that

performing multiple analyses could lead to false positive results.

Prevalence of medication was self-reported and if not so, chart information was used, with a

risk of being outdated and missing non-prescription drugs. Medication can bias findings; i.e. anxiolytics

and antidepressants can decrease symptoms of anxiety and depression, and PPIs are not recommended

immediately before gastroscopy [1,9].

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It has been shown that up to 10% of ulcers are overlooked by endoscopists [1,3,10], making

this a random error. Important to note is also that not all OG patients had dyspeptic symptoms, and could

be asymptomatic. Future studies may match FD-patients with patients with organic pathology of same

symptom burden. At the same time, ulcus disease, gastroesophageal reflux disease (GERD) or gastritis do

not necessarily have to be the cause of symptoms [4,11,42], and caution should be taken because FGIDs

can coexist with organic disease. For example, reflux and dyspepsia can coexist and be hard to

differentiate [1,2,4,14,18]. Future studies may implement the use of pH-measurements, since patients may

suffer from non-erosive gastroesophageal reflux which does not result in macroscopically visible findings

on endoscopy.

Today, FD-patients are provided with information [1–4,9–11] and ineffective

pharmacotherapy such as PPIs, TCAs’ and prokinetics. However, the impact of psychological factors

affects QoL, health care utilization, work absenteeism, compliance, outcome of treatment and therefore

lead to more burden for both the patient and the health care system. It is unclear whether psychological

distress motivates or hinder patients to seek health care, but excessive health care utilisation should alert

clinicians to risk for psychiatric comorbidity [6]. A large proportion of anxiety- and depression symptoms

never catches the gastroenterologists attention [28]. Hence it is important to assess these patients

adequately with the right approach, and new insights may contribute to a more effective and holistic one,

preferable in a multidisciplinary setting. Therapy focusing on psychological factors may be appropriate

for at least a subset of patients, and by learning more we will hopefully be able to identify those patients

that may benefit from this.

Conclusion In this study, the functional dyspepsia group had a higher frequency of dyspeptic symptoms and lower

QoL, as well as higher levels of anxiety, depression and neuroticism, compared to patients with

pathologic gastroscopic findings. These factors are likely to be complexly intertwined, affecting health

care seeking and patient outcome. Our study contributes to understanding dyspepsia pathology, and can

contribute to reduce the burden on patients, as well as society, via a better way of managing these patients

in the future. This pilot study is also an important contribution for designing larger studies yet to come in

this field.

12  

References 1. Agréus MS Lars. Sjukdomar i matstrupe, magsäck och tolvfingertarm | Läkemedelsboken [Internet].

[cited 2017 Oct 3]. Available from: https://lakemedelsboken.se/kapitel/mage-tarm/sjukdomar_i_matstrupe_magsack_och_tolvfingertarm.html?id=b1_4#b1_4

2. Lindgren S, Engström-Laurent A, Karason K, Tiensuu Janson E. Medicin. Lund: Studentlitteratur; 2017.

3. Hultcrantz R, Bergquist A, Lindgren S, Simrén M, Stål P, Suhr OB. Gastroenterologi och hepatologi. Stockholm: Liber; 2011.

4. Nyhlin H, Ahlman B. Medicinska mag- och tarmsjukdomar [Internet]. Lund: Studentlitteratur; 2008 [cited 2017 Oct 3]. Available from: http://www.studentlitteratur.se/cache/ttf/0111a50620116ef7c1.gif

5. Ayuo PO, Some FF, Kiplagat J. Upper Gastrointestinal Endoscopy Findings in Patients Referred With Upper Gastrointestinal Symptoms in Eldoret, Kenya: A Retrospective Review. East Afr Med J. 2014;91(8):267–273.

6. Mak ADP, Wu JCY, Chan Y, Chan FKL, Sung JJY, Lee S. Dyspepsia is strongly associated with major depression and generalised anxiety disorder - a community study. Aliment Pharmacol Ther. 2012 Oct;36(8):800–10.

7. Ebling B, Jurcic D, Barac KM, Bilic A, Bajic I, Martinac M, et al. Influence of various factors on functional dyspepsia. Wien Klin Wochenschr. 2016 Jan;128(1–2):34–41.

8. Gyedu A, Yorke J. Upper gastrointestinal endoscopy in the patient population of Kumasi, Ghana: Indications and findings. Pan Afr Med J [Internet]. 2014 [cited 2017 Nov 20];18. Available from: http://www.panafrican-med-journal.com/content/article/18/327/full/

9. Dahlström U, Kechagias S, Stenke L. Internmedicin. Stockholm: Liber; 2011.

10. Lindberg G, Nyhlin H. Gastroenterologi och hepatologi. Lund: Studentlitteratur; 2016.

11. Kumar PJ, Clark ML. Kumar & Clark’s clinical medicine. Edinburgh: Elsevier; 2016.

12. Dibaise JK, Islam RS, Dueck AC, Roarke MC, Crowell MD. Psychological distress in Rome III functional dyspepsia patients presenting for testing of gastric emptying. Neurogastroenterol Motil. 2016 Feb;28(2):196–205.

13. Mahadeva S, Wee H-L, Goh K-L, Thumboo J. Quality of life in South East Asian patients who consult for dyspepsia: Validation of the short form Nepean Dyspepsia Index. Health Qual Life Outcomes. 2009;7(1):45.

14. Irvine AJ, Pinto-Sanchez MI, Bercik P, Moayyedi P, Ford AC. Minimal differences in prevalence and spectrum of organic disease at upper gastrointestinal endoscopy between selected secondary care patients with symptoms of gastro-oesophageal reflux or dyspepsia. Scand J Gastroenterol. 2017 Apr 3;52(4):396–402.

15. Shetty AJ, Balaraju G, Shetty S, Pai CG. Quality of life in dyspepsia and its subgroups using EQ-5D (EuroQol) questionnaire. Saudi J Gastroenterol Off J Saudi Gastroenterol Assoc. 2017;23(2):112.

13  

16. Koloski NA, Jones M, Talley NJ. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study. Aliment Pharmacol Ther. 2016 Sep;44(6):592–600.

17. Lee YY, Wahab N, Mustaffa N, Daud N, Noor NM, Shaaban J, et al. A Rome III survey of functional dyspepsia among the ethnic Malays in a primary care setting. BMC Gastroenterol. 2013;13(1):84.

18. Aro P, Talley NJ, Johansson S-E, Agréus L, Ronkainen J. Anxiety Is Linked to New-Onset Dyspepsia in the Swedish Population: A 10-Year Follow-up Study. Gastroenterology. 2015 May;148(5):928–37.

19. Nan J, Liu J, Li G, Xiong S, Yan X, Yin Q, et al. Whole-Brain Functional Connectivity Identification of Functional Dyspepsia. Zuo X-N, editor. PLoS ONE. 2013 Jun 17;8(6):e65870.

20. Liu P, Zeng F, Zhou G, Wang J, Wen H, von Deneen KM, et al. Alterations of the default mode network in functional dyspepsia patients: a resting-state fmri study. Neurogastroenterol Motil. 2013 Jun;25(6):e382–8.

21. Nan J, Liu J, Zhang D, Yang Y, Yan X, Yin Q, et al. Altered intrinsic regional activity and corresponding brain pathways reflect the symptom severity of functional dyspepsia. Neurogastroenterol Motil. 2014 May;26(5):660–9.

22. Liu P, Qin W, Wang J, Zeng F, Zhou G, Wen H, et al. Identifying Neural Patterns of Functional Dyspepsia Using Multivariate Pattern Analysis: A Resting-State fMRI Study. Zang Y-F, editor. PLoS ONE. 2013 Jul 12;8(7):e68205.

23. Zeng F, Qin W, Yang Y, Zhang D, Liu J, Zhou G, et al. Regional Brain Structural Abnormality in Meal-Related Functional Dyspepsia Patients: A Voxel-Based Morphometry Study. Paul F, editor. PLoS ONE. 2013 Jul 2;8(7):e68383.

24. Cirillo C, Bessissow T, Desmet A-S, Vanheel H, Tack J, Vanden Berghe P. Evidence for neuronal and structural changes in submucous ganglia of patients with functional dyspepsia. Am J Gastroenterol. 2015 Aug;110(8):1205–15.

25. Filipović BF, Randjelovic T, Ille T, Markovic O, Milovanović B, Kovacevic N, et al. Anxiety, personality traits and quality of life in functional dyspepsia-­‐suffering patients. Eur J Intern Med. 2013 Jan;24(1):83–6.

26. Jamil O, Sarwar S, Hussain Z, Fiaz RO, Chaudary RD. Association Between Functional Dyspepsia and Severity of Depression. J Coll Physicians Surg--Pak JCPSP. 2016 Jun;26(6):513–6.

27. Jiang S-M. Incidence and psychological-behavioral characteristics of refractory functional dyspepsia: A large, multi-center, prospective investigation from China. World J Gastroenterol. 2015;21(6):1932.

28. Pinto-Sanchez MI, Ford AC, Avila CA, Verdu EF, Collins SM, Morgan D, et al. Anxiety and depression increase in a stepwise manner in parallel with multiple FGIDs and symptom severity and frequency. Am J Gastroenterol. 2015;110(7):1038.

29. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–70.

14  

30. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606–13.

31. John OP, Robins RW, Pervin LA. Handbook of Personality  : theory and research. New York, NY: Guilford Press; 2010.

32. Masic I, Hodzic A, Mulic S. Ethics in medical research and publication. Int J Prev Med. 2014;5(9):1073.

33. Coskun A, Yukselen V, Meteoglu I, Ergin F, Kadikoylu G, Yasa MH, et al. H. pylori positivity and various pathological, endoscopic and clinical features correlated with each other. J Pak Med Assoc. 2015;65:1305–1309.

34. Yu J. Gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia. World J Gastroenterol. 2013;19(32):5357.

35. Cardin F, Andreotti A, Zorzi M, Terranova C, Martella B, Amato B, et al. Usefulness of a fast track list for anxious patients in a upper GI endoscopy. BMC Surg. 2012;12(Suppl 1):S11.

36. Agréus L, Simrén M. Nya riktlinjer för handläggning av dyspepsi, H pylori och mags\a ar. Lakartidningen. 2017;114.

37. von Knorring L, Hedin K, von Knorring A-L. \AAngest och oro| Läkemedelsboken. 2015;

38. Socialstyrelsen. Depression [Internet]. Kunskapsguiden.se. 2016 [cited 2018 Jan 3]. Available from: http://www.kunskapsguiden.se/psykiatri/Teman/Depression/Sidor/default.aspx

39. Tominaga K, Tsumoto C, Ataka S, Mizuno K, Takahashi K, Yamagami H, et al. Regional brain disorders of serotonin neurotransmission are associated with functional dyspepsia. Life Sci. 2015 Sep;137:150–7.

40. Vanheel H, Vicario M, Vanuytsel T, Van Oudenhove L, Martinez C, Keita ÅV, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut. 2014 Feb;63(2):262–71.

41. Walker MM, Aggarwal KR, Shim LS, Bassan M, Kalantar JS, Weltman MD, et al. Duodenal eosinophilia and early satiety in functional dyspepsia: Confirmation of a positive association in an Australian cohort: Duodenal eosinophilia and dyspepsia. J Gastroenterol Hepatol. 2014 Mar;29(3):474–9.

42. Vasiliou C, Xiromeritou V, Kafiri G, Papatheodoridis G. Endoscopic and Histological Findings and Helicobacter pylori Status in Patients With Reflux and/or Dyspeptic Symptoms: A Recent Greek Cohort Study. Gastroenterol Nurs. 2014;37(6):431–8.

Appendix Informational letter with inquiry of participation and medication record form

Förfrågan om deltagande i studie

Skriftlig information till deltagare Personlighet och psykiskt mående har betydelse för vårt generella välbefinnande, inte minst gäller detta besvär i magtarmkanalen. Vi genomför just nu en studie vid Medicinska kliniken (avdelning Gastroenterologi) på Universitetssjukhuset i Örebro och vid Örebro Universitet. Denna studie undersöker sambandet mellan symtom från magtarmkanalen (såsom smärta, obehag, brännande känsla, tidig mättnadskänsla och ”uppkördhet” efter måltid) och personlighetstyp, psykiskt mående och fynd på gastroskopiundersökning. Vi vänder oss till Dig för att tillfråga dig om deltagande i studien, då Du stått med på väntelista till gastroskopi på Medicinska kliniken. Studien innefattar 4 korta enkäter och ett blad där du får skriva ner vilka läkemedel du tar. Vi vill be dig att fylla i enkäterna och listan över läkemedel hemma och ta med dem ifyllda till Endoskopimottagningen. Gastroskopiundersökningen kommer att utföras på sedvanligt sätt och innebär inte något extra ingrepp. Endast de personer som arbetar med studien kommer ha tillgång till Dina uppgifter och inga obehöriga kommer kunna ta del av dem. Alla Dina uppgifter hanteras enligt Personuppgiftslagen och Patientdatalagen, och kommer presenteras utan namn eller personnummer så att de inte ska kunna knytas till Dig. Deltagandet i studien är helt frivilligt. Om Du väljer att inte delta kommer detta inte påverka vilket omhändertagande du får i fortsättningen. Om Du är intresserad kan Du vid studiens slut ta del av dess resultat genom att kontakta ansvariga. Tack på förhand för ditt samarbete Om du har några frågor kan du höra av dig till: Otilia Siversten, Läkarkandidat, mejl: otisiv131@studentmail.oru.se M. A. Van Nieuwenhoven, Överläkare, Docent Invärtesmedicin och Gastroenterologi

Samtycke till deltagande i studie

Informerat samtycke Jag har tagit del av information kring studien och fått svar på de eventuella frågor jag haft. Jag samtycker härmed till deltagandet i studien och att mina uppgifter används i den: � (Sätt kryss i rutan) --------------------------------------------- Underskrift --------------------------------------------- Namnförtydligande --------------------------------------------- Ort och datum

Läkemedelslista Var vänlig och skriv ner de läkemedel du tar, alternativt ta med en giltig läkemedelslista som innehåller alla de läkemedel du tar, både stående och tillfällig medicinering ska stå med.

PREPARATNAMN STYRKA DOSERING SEDAN HUR LÄNGE HAR DU

TAGIT LÄKEMEDLET?

 

Short Form Nepean Dyspepsia Index (Swedish)

NEPEAN DYSPEPSI FRÅGEFORMULÄR - KORTVERSION

SF-NDIâ

Tack för att du hjälper oss med den här undersökningen. Det här frågeformuläret innehåller detaljerade

frågor om dina magbesvär och hur de påverkar dig och ditt liv.

En del av frågorna är ganska personliga, men informationen som du lämnar kommer att behandlas med

sekretess och känslighet.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

SF-NDIÓ Nicholas J Talley, 1998

Detta är den ÖVRE DELEN AV BUKEN (magen)  

Naveln  

 

Nepean  dyspepsi  frågeformulär  -­  kortversion  (SF-­NDI)©    Var  vänlig  SKRIV  SIFFROR  i  tabellen  nedan  för  att  ange  hur  ofta  du  har  haft  magbesvär  under  de  senaste  14  DAGARNA  och  hur  intensiva  och  besvärande  de  har  varit.  Illustrationen  på  framsidan  visar  den  ”ÖVRE  DELEN  AV  BUKEN”  –  var  vänlig  titta  på  illustrationen  när  du  svarar  på  frågor  om  besvär  i  den  ”ÖVRE  DELEN  AV  BUKEN”.  

 Under  de  senaste    

14  dagarna,  hade  du  något  av  följande  MAGBESVÄR?  

Hur  MÅNGA  DAGAR  hade  du  

det?  0  =  Inga  alls  1  =  En  till  fyra  dagar  2  =  Fem  till  åtta  dagar  3  =  Nio  till  tolv  dagar  4  =  Varje  dag/nästan  

varje  dag  

Om  du  upplevde  detta  symptom,    

hur  INTENSIVT  var  det  vanligtvis?  0  =  Inte  alls  1  =  Väldig  svagt  2  =  Svagt  3  =  Måttligt  4  =  Kraftigt  5  =  Väldigt  kraftigt  

Om  du  upplevde  detta  symptom,    

hur  BESVÄRANDE  var  det?  

0  =  Inte  alls  1  =  Lite  grann  2  =  Måttligt  3  =  Mycket  4  =  Extremt  mycket  

Smärta  eller  värk  i  den  övre  delen  av  buken  (magen)  

     

Obehag  i  den  övre  delen  av  buken  (magen)        

Brännande  känsla  i  den  övre  delen  av  buken  (magen)  

     

Brännande  känsla  i  bröstet  (halsbränna)        

Kramper  i  den  övre  delen  av  buken  (magen)        

Smärta  eller  värk  i  bröstet,  ovanför  magen        

Oförmåga  att  avsluta  en  vanlig  måltid        

Bitter/sur  vätska  som  kommer  upp  i  din  mun  eller  hals  

     

Tidig  mättnadskänsla  vid  måltid  eller  långsam  matsmältning  

     

Tryck  i  den  övre  delen  av  buken  (magen)        

Känsla  av  uppsvälldhet  i  magen        

Illamående        

Rapningar        

Kräkningar        

Dålig  andedräkt        

Spänningar    1.   Har  ditt  ALLMÄNNA  KÄNSLOMÄSSIGA  VÄLBEFINNANDE  blivit  stört  av  dina  

magbesvär  under  de  senaste  14  dagarna?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket  

 2.   Har  du  varit  LÄTTRETLIG,  SPÄND  eller  FRUSTRERAD  under  de  senaste    

14  dagarna  på  grund  av  dina  magbesvär?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket  

   Störning  av  dagliga  aktiviteter  

   

3.   Har  din  FÖRMÅGA  att  engagera  dig  i  saker  som  du  vanligtvis  gör  som  FRITIDSAKTIVITET  (som  rekreation,  uteliv,  hobbies,  sport  mm)  blivit  störd  av  dina  magbesvär  under  de  senaste  14  dagarna?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket    

4.   Har  din  GLÄDJE  av  det  du  vanligtvis  gör  som  FRITIDSAKTIVITET  (som  rekreation,  uteliv,  hobbies,  sport  mm)  blivit  störd  av  dina  magbesvär  under  de  senaste  14  dagarna?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket  6   Ej  tillämpligt   (Jag  har  inte  kunnat  göra  någon  av  dessa  saker  under  de  

senaste  14  dagarna,  på  grund  av  mina  magbesvär)  

Att  äta/dricka      

5.   Har  din  FÖRMÅGA  att  ÄTA  eller  DRICKA  (inklusive  när,  vad  och  hur  mycket)  blivit  störd  av  dina  magbesvär  under  de  senaste  14  dagarna?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket    

6.   Har  din  GLÄDJE  av  att  ÄTA  och/eller  DRICKA  störts  av  dina  magbesvär  under  de  senaste  14  dagarna?  (Inkludera  din  aptit  och  hur  du  mår  efter  mat  eller  dryck).    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket  

   Kunskap  om/kontroll  över  magbesvären      7.   Under  de  senaste  14  dagarna,  har  du  UNDRAT  om  du  ALLTID  kommer  att  ha  de  

här  magbesvären?    1   Nästan  aldrig  2   Ibland  3   Ofta  4   Väldigt  ofta  5   Ständigt  

 8.   Under  de  senaste  14  dagarna,  har  du  UNDRAT  om  dina  magbesvär  kan  bero  på  en  

mycket  ALLVARLIG  sjukdom  (såsom  cancer  eller  hjärtproblem)?    1   Nästan  aldrig  2   Ibland  3   Ofta  4   Väldigt  ofta  5   Ständigt  

Arbete/hushållsarbete/studier      9.   Har  din  FÖRMÅGA  att  ARBETA,  STUDERA  eller  göra  HUSHÅLLSARBETE  störts  av  

dina  magbesvär  under  de  senaste  14  dagarna?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket  6   Ej  tillämpligt   (Jag  har  inte  arbetat,  studerat  eller  gjort  hushållsarbete  

under  de  senaste  14  dagarna,  på  grund  av  mina  magbesvär)      10.   Har  din  GLÄDJE  av  att  ARBETA,  STUDERA  eller  göra  HUSHÅLLSARBETE  störts  av  

dina  magbesvär  under  de  senaste  14  dagarna?    1   Inte  alls  2   Lite  grann  3   Måttligt  4   Mycket  5   Extremt  mycket  6   Ej  tillämpligt   (Jag  har  inte  arbetat,  studerat  eller  gjort  hushållsarbete  

under  de  senaste  14  dagarna,  på  grund  av  mina  magbesvär)      Poängräkning:  Summera  poängen  för  vart  och  ett  av  de  fem  områdena  (varje  område  kan  få  2-­‐10  poäng).  

Patient Health Questionnaire-9 (Swedish)

F O R M U L Ä R F Ö R P A T I E N T H Ä L S A - 9 ( P H Q - 9 )

Under de senaste 2 veckorna, hur ofta har du besvärats av något/några av följande problem? (Sätt en bock “✔” bredvid ditt svar) Inte alls

Flera dagar

Mer än hälften

av dagarna

Nästan varje dag

1. Lite intresse eller glädje av att göra saker 0 1 2 3

2. Känt dig nedstämd, deprimerad eller upplevt känsla av hopplöshet 0 1 2 3

3. Svårigheter att somna eller få en sammanhängande sömn, eller sovit för mycket 0 1 2 3

4. Känt dig trött eller haft för lite energi 0 1 2 3

5. Dålig aptit eller ätit för mycket 0 1 2 3

6. Tycker illa om dig själv – eller att du känt dig misslyckad eller att du svikit dig själv eller din familj 0 1 2 3

7. Svårigheter att koncentrera dig på saker, till exempel att läsa tidningen eller att titta på TV 0 1 2 3

8. Att du rört dig eller talat så långsamt att andra människor märkt det? Eller motsatsen – att du varit så nervös eller rastlös att du rört dig mer än vanligt

0 1 2 3

9. Tankar att det skulle vara bättre om du var död eller att du skulle skada dig på något sätt 0 1 2 3

FOR OFFICE CODING 0 + ______ + ______ + ______

=Total Score: ______

Om du svarat att du haft något av dessa problem, hur svårt har dessa problem gjort det för dig att utföra ditt arbete, ta hand om saker hemma, eller att komma överens med andra människor?

Inte alls svårt �

Lite svårt �

Mycket svårt �

Extremt svårt �

Framtagen av läkarna Robert L. Spitzer, Janet B.W. Williams, Kurt Kroenke och kollegor, med ett utvecklingsanslag från Pfizer Inc. Ingen tillåtelse krävs för att reproducera, översätta, visa eller distribuera.

Hospital Anxiety and Depression Scale (Swedish)

Hospital Acquired Depression Scale

Fyll i det alternativ som stämmer bäst in på Dig! Jag känner mig spänd eller nervös: Allting känns trögt: ( ) Mestadels ( ) Nästan alltid ( ) Ofta ( ) Ofta ( ) Av och till ( ) Ibland ( ) Inte alls ( ) Aldrig Jag uppskattar fortfarande saker jag Jag känner mig orolig, som om jag har tidigare uppskattat: ”fjärilar” i magen: ( ) Definitivt lika mycket ( ) Aldrig ( ) Inte lika mycket ( ) Ibland ( ) Endast delvis ( ) Ganska ofta ( ) Nästan inte alls ( ) Väldigt ofta Jag har en känsla av att något hemskt Jag har tappat intresset för hur jag ser kommer att hända: ut: ( ) Mycket klart och obehagligt ( ) Fullständigt ( ) Inte så starkt nu ( ) Till stor del ( ) Betydligt svagare nu ( ) Delvis ( ) Inte alls ( ) Inte alls Jag kan skratta och se det roliga i saker Jag känner mig rastlös: och ting: ( ) Väldigt ofta ( ) Lika ofta som tidigare ( ) Ganska ofta ( ) Inte lika ofta nu ( ) Sällan ( ) Betydligt mer sällan nu ( ) Inte alls ( ) Aldrig Jag ser med glädje fram emot saker och Jag bekymrar mig över saker: ting: ( ) Mestadels ( ) Lika mycket som tidigare ( ) Ganska ofta ( ) Mindre än tidigare ( ) Av och till ( ) Mycket mindre än tidigare ( ) Någon enstaka gång ( ) Knappast alls Jag känner mig på gott humör: Jag får plötsliga panikkänslor: ( ) Aldrig ( ) Väldigt ofta ( ) Sällan ( ) Ganska ofta ( ) Ibland ( ) Sällan ( ) Mestadels ( ) Aldrig Jag kan sitta stilla och känna mig Jag kan uppskatta en god bok, eller ett avslappnad: TV- eller radioprogram ( ) Definitivt ( ) Ofta ( ) Vanligtvis ( ) Ibland ( ) Sällan ( ) Sällan ( ) Aldrig ( ) Mycket sällan

The Big Five Inventory (Swedish)

COVER LETTER Journal of xxxxx

2nd of January 2017 Dear Editor, Please consider publishing the enclosed manuscript entitled “Psychological Profile in Patients with Pathologic Gastroscopic Findings and Functional Dyspepsia: A Pilot Study” in Your Journal. We think that this could be of interest to readers because of the following reasons:

•   This is one of few studies investigating the association between functional dyspepsia and not only features of anxiety and depression, but also personality traits, compared to patients with pathologic gastroscopic findings.

•   To our knowledge, this is the first study on gastroscopy patients using the validated Big Five Inventory-Questionnaire to assess personality traits. This showed higher levels of neuroticism in functional dyspeptics.

•   Comparing functional dyspeptics to patients with pathologic gastroscopic findings, the functional group had a higher frequency of dyspeptic symptoms, lower quality of life and higher levels of anxiety and depression (while the group with pathologic gastroscopic findings were more in line with population norms).

•   The study was done with respect to the common population in everyday clinical work, so results are generalizable to many clinics around the world.

•   Our study contributes to understanding dyspepsia pathology, and can contribute to reduce the burden on patients, as well as society, via a better way of managing these patients in the future.

•   This pilot study is an important contribution for designing larger studies yet to come in this field.

The authors declare no conflicts of interest. This manuscript has not been published, nor is it for consideration elsewhere. Yours sincerely, Otilia Siversten Örebro Sweden  

POPULÄRVETENSKAPLIG SAMMANFATTNING Dyspepsi innebär symtom från övre magen, såsom smärta, obehag, brännande

känsla, uppkördhet och tidig mättnadskänsla. Dyspepsi är vanligt och kan bero på sjukdom i övre magen eller att man inte hittar någon orsak, så kallad funktionell dyspepsi. Det finns ingen bra behandling för funktionell dyspepsi, som ofta ger långdragna problem. Forskning har visat att patienter med funktionell dyspepsi har lägre livskvalitet samt att sjukdomen har ett samband med psykologiska och psykiatriska faktorer, såsom ångest och depression. Detta ger lidande och hög sjukfrånvaro, och vidare höga kostnader för samhället. För att minska detta ville vi genomföra en studie som kunde bidra till förståelse för sjukdomen. I forskningsstudien delades enkäter ut till patienter som skulle genomföra gastroskopi. Det visade sig att patienter med funktionell dyspepsi oftare hade

dyspepsisymtom samt lägre livskvalitet jämfört med gruppen med sjukdomsfynd (via gastroskopi). Patienterna med funktionell dyspepsi hade också mer symtom på ångest och depression, och mer neurotiska personlighetsdrag. Alla ovanstående komponenter samspelar troligen i ett komplicerat samband mellan hjärna och mage. Med varje studie lär vi oss mer om hur detta fungerar och kan förhoppningsvis använda detta till bättre bemötande och behandling för patienterna.

Magsårssjukdom; ett exempel på sjukdom i övre magen som kan ses med hjälp av gastroskopi.

ETISK REFLEKTION Etik är en av grundstenarna för att modern forskning ska vara tillämpbar i vårt samhälle, något nuvarande regler/lagar och Helsingforsdeklarationen bidrar till. I forskning innefattande forskningspersoner är det till exempel viktigt med information om projektet (vem, vad, var, hur, varför) samt en otvingad förfrågan om deltagande (vilket ska vara frivilligt). Det är också av vikt att forskningspersonen vet att information behandlas med sekretess och presenteras avidentifierat, och att hen kan dra sig ur utan att detta påverkar framtida vård. Om personen i fråga har frågor måste det finnas utrymme för sådana. Transparens är oumbärlig för att forskningspersonen ska kunna ta ett välgrundat beslut om deltagande, och är en indikation på att forskningen sker på ett tillförlitligt och professionellt sätt.

För- och nackdelar är likaså viktiga för forskningspersonens beslut, och ska alltid vägas samman av forskare och etiknämnd för att avgöra om forskningsprojektet är genomförbart. I just vår studie var nackdelarna inte särskilt påtagliga, gastroskopiundersökningen (som utfördes på sedvanligt sätt) utgjorde inte något extra ingrepp. Fördelarna var däremot ett bidrag till utvidgning av kunskapsbasen kring forskningsämnet, för att hitta ett bättre förhållningssätt och framtida behandling.

Forskning kring psykisk hälsa kan vara känsligt och det är därför extra viktigt med ovanstående punkter. Ett exempel är hur man hanterar forskningspersoner med ångest/depression. Kanske ska man erbjuda hjälp, men samtidigt ska uppgifterna avidentifieras, och i vår studie fanns ingen psykiatrisk intervention. Man kan också argumentera att uppsökande av vård sker när patienten känner sig redo för det, kanske bidrar till exempel enkäter till sjukdomsinsikt.    

Gastroskopi: Gastroskopi innebär att man tittar

ner i magsäcken och första delen av tunntarmen med en liten kamera,

för att se om det finns någon sjukdom eller avvikelse där. Om

man inte hittar någon sådan hos en patient med dyspepsi blir diagnosen

”Funktionell dyspepsi”.