mak et al-2012-alimentary pharmacology & therapeutics

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INTRODUCTION

Dyspepsia is a common gastrointestinal condition that is

characterised by chronic recurrent epigastric symptoms

such as pain, burning and postprandial symptoms. Dys-

pepsia is associated with signicant functional impair-

ment and burden on healthcare resources.1 Estimates of

community prevalence of dyspepsia have varied widely

from 5% to 40%2 depending on criteria used. Yet,

community prevalence measured using strictly applied

Rome III criteria,3 which are more precise and restrictive

than their predecessors, remains sparse.4

It has been reported that comorbid psychiatric disor-

ders are common in patients with dyspepsia. Generalised

anxiety disorder (GAD) and Major depressive episodes

(MDE), in particular, have been most extensively related

to dyspepsia. These three disorders share several

commonalities. Similar to functional dyspepsia, both

GAD and MDE are typically chronic and relapsing, more

common in female, with onset and exacerbation oftenassociated with psychosocial stress.5, 6 Moreover, visceral

hypersensitivity and somatisation have been associated

with all three conditions.4, 7 – 10

Studies have found increased anxiety and depressive

symptoms on rating scales,11 and poorer psychological

wellbeing 12 in organic and functional dyspepsia. How-

ever, their relevance to how specic comorbid mental

disorders may contribute to the clinical and societal

burden of dyspeptic symptoms12 remains unclear. As

effective interventions exist for mental disorders,

their treatment may benet the clinical outcome of dyspepsia.13

To date, most studies on psychiatric correlates in dys-

peptic patients came from referral centres and clinics.4

Selection bias may distort any association of psychiatric

morbidity and dyspepsia found in these samples, because

only 25 – 42%14 of dyspepsia sufferers in the community

seek medical care. It is unclear whether psychological

distress may motivate or hinder patients in seeking care

for dyspeptic symptoms. The recent community-based

Kalixanda study 15 evaluated the relationship between

anxiety, depression and functional dyspepsia. It foundanxiety, but not depression, to be associated with func-

tional and organic dyspepsia. However, the Rome III

criteria used in this study were post hoc rated from a

Rome II questionnaire with the Rome III 6-month onset

criterion discarded. Meanwhile, HADS, as with most

psychiatric symptom scales, captured symptoms as a

dimensional score, and did not meet the duration

and impairment requirements for diagnosis of GAD

and MDE as mental disorders dened by the American

Psychiatric Associations’ Diagnostic and Statistical

Manual of Mental Disorders, Fourth Edition- Text

Revision (DSM-IV-TR)16 (Tables 2 and 3). Using the

Structured Clinical Interview for DSM-IV Axis-I

Disorder (SCID-I),17 we found 38.2% and 16.4% of

Chinese patients in a tertiary gastroenterology clinic with

functional dyspepsia to have an anxiety disorder and

depressive disorder respectively.18

We therefore set out to conduct a community survey

to examine the current community prevalence of strin-

gently dened Rome III Dyspepsia (Table 1), as well as

the 12-month prevalence of GAD and MDE using

DSM-IV-TR. We also evaluated the association between

dyspepsia, GAD and MDE and the chronological

relationship of their onsets. Although rarely examined

in previous studies, the latter may shed light on

whether these illnesses may be causally related to each

other.19

METHODS

A random community-based telephone survey of the

general population in the age range of 15 – 65 years was

conducted from 22nd April to 13th May, 2009. The

study was approved by the research ethics committee of

The Chinese University of Hong Kong. The Hong Kong

Institute of Asia-Pacic Studies of the Chinese University

of Hong Kong, an independent survey research organisa-

tion, was commissioned to conduct the survey. Inter-

viewers were university students with 1 – 3 years of

part-time experience in telephone interviews. A brieng session was held by the investigators (AM, JW, YC) for

training of administration of the questionnaire and

explaining skills involved in eliciting symptoms of dys-

pepsia, GAD and MDE. Respondents were invited to

take part in a telephone survey of ‘digestive problems

and emotional health’. Interviews proceeded only after

verbal consent was sought. The interviews were

conducted in Cantonese dialect, the predominant spoken

Table 1 | Rome III symptomatic criteria for functionaldyspepsia

3

Must include

One or more of

a Bothersome postprandial fullness

b Early satiation

c Epigastric pain

d Epigastric burning

Criteria fullled for the last 3 months with symptom onset at

least 6 months before diagnosis.

Aliment Pharmacol Ther 2012; 36: 800-810 801ª 2012 Blackwell Publishing Ltd

Community study on dyspepsia, depression and anxiety


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MDE (Tables 2 and 3) based on DSM-IV-TR Criteria

and healthcare utilisation.

The same questionnaire for GAD and MDE diagnoses

had been used in previous series of telephone surveys

that found 12-month prevalence of GAD to be 4.1%22

and 8.4% for major depressive episode (MDE).23 Clinical

re-appraisal for diagnoses of MDE and GAD using the

gold standard of psychiatric diagnosis in research, the

Table 3 | Survey questions pertaining to the DSM IV-TR symptoms of major depressive episode

DSM – IV criteria Questions in the telephone survey

Required response for

diagnosis

FIVE or more of the following in the same

2 week period, representing a change from

previous functioning. At least ONE should

be either (1) or (2)1. Depressed mood most of the day, nearly

every day (reported or observed)

2. Markedly diminished interest or pleasure

in (almost) all activities most of the day,

nearly every day (reported or observed)

3. Signicant weight loss

4. Insomnia or hypersomnia nearly every

day

5. Psychomotor agitation or retardation

nearly every day (observed + subjective)

6. Fatigue or loss of energy nearly every day

7. Feelings of worthlessness or excessive or

inappropriate guilt nearly every day (not

merely self-reproach or guilt about beingsick)

8. Diminished ability to think or

concentrate, or indecisiveness, nearly

every day (subjective or objective)

9. Recurrent thoughts of death (not just fear

of dying), recurrent suicidal ideation

without a specic plan, or a suicide

attempt or a specic plan for committing

suicide.

A1. In the past year, have you had 2 weeks

or longer when you had depressed mood

most of the day, nearly every day?

A2. In the past year, have you had 2 weeksor longer when you had markedly reduced

interest or pleasure in almost all activities

most of the time, nearly every day?

‘Yes’ in A1 or A2

B. During the period when you had

(depressed mood) (reduced interest or

pleasure), did you often have

a Poor appetite or lost weight

b Slept less than usual

c Observable slowing of speech or actions

d Fatigue or loss of energy

e Difculty to concentrate or make

decisions

f Observable restlessness and agitation

g Increased appetite or body weight

h Slept more than usual

i Felt worthless

j Thoughts of death or suicide

a and g counted as 1

item

b and h counted as 1

item

c and f counted as 1

item

‘Yes’ in at least FIVE

items in sections A and

B, including at least one

item in A.

D. Clinically signicant distress or

impairment in social, occupational/other

important areas of functioning

D1. Did the above experiences cause you

signicant distress? AND/OR

‘Very distressed’ or

‘Quite distressed’ AND/

OR

D. Clinically signicant distress orimpairment in social, occupational/other

important areas of functioning

D2. Did the above experiences signicantlyimpair your daily life (e.g. study/work,

social & family life?

‘Very impaired’ or ‘Quiteimpaired’




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Structured Clinical Interview for DSM-IV Axis-I Disor-

ders (SCID-I) yielded good agreement.24, 25 The same

series of telephone survey had assessed prevalence of Rome III Irritable Bowel Syndrome in Hong Kong to be

5.4%, comparable while conservative, with overseas esti-

mates.26

We also asked ‘how much did you spend over the past

5 years on investigations for your gastrointestinal

problems?’ to assess investigation expenditure and ‘how

frequently did you see a doctor for your health problems’

to assess frequency of consultations. Subjects were also

asked for each disorder their respective ages when the

disorder rst came on in their lives so as to estimate

chronological association of the disorders.

Study power

Power calculation was performed post hoc based on the

sample collected to estimate the size of odds ratio that

can be detected in the whole sample and the dyspepsia

subgroup. With an overall sample (n = 2011), a logistic

regression of binary response variable of dyspepsia

(n = 142, 7% dyspepsia without MDE) on the binary

independent variable of GAD (n = 77, 3.8%), to

achieve 80% power at a signicance level of 0.05, will

have a minimum detectable odds ratio of 2.60. For

the dyspepsia-only subgroup (n = 161), for logistic

regression of binary response variable of GAD (n = 4,

4% GAD without MDE) on the binary independent vari-

able of MDE (n = 53, 33%), the minimum detectable

odds ratio would be 5.24, to achieve 80% power at a sig-

nicance level of 0.05.27

Analysis

The current prevalence of dyspepsia and 12-month prev-

alence of generalised anxiety disorder and major depres-

sive episode were presented as percentages. The study

sample was weighted (Appendix S1) according to age and

sex distribution of the Hong Kong general population

based on the 2008 Census data (Table 4). To identify

Phone calls made withvalid telephone numbers

(n = 6378)

No suitable respondent(n = 720)

n = 3793

Interview refused by otherfamily members (n = 931)

n = 2862

n = 2142

Hung up immediately(n = 2585)

n = 2093

Failure to contactsuitable respondent (n = 49)

Successfully interviewedrespondents n = 2011

Refused by suitablerespondent (n = 82)

Figure 1 | Flow diagram depicting various reasons for

and number of subjects who did not participate in the

study.

Table 4 | Sociodemographic characteristics of the

respondents and comparison with Hong Kong Census

data

Total sample

(n = 2011), % (n)

% Census

2008*

Gender

Male 46.6 (937) 47.2

Female 53.4 (1074) 52.8

Age

15 – 24 16.9 (341) 17.0

25 – 34 20.4 (411) 20.4

35 –

44 22.5 (454) 22.645 – 54 24.3 (488) 24.2

55 – 65 15.8 (317) 15.8

Education

Primary or below 11.3 (317) –

Secondary 45.2 (905) –

Pre college 10.3 (206) –

College or above 33.3 (667) –

Work status

Employed 60.6 (1212) –

Unemployed 6.4 (129) –

Retired 7.0 (141) –

Student 12.1 (241) –

Homemaker 13.8 (278) –

Marital statusSingle 38.4 (769) –

Married/living together 59.4 (1190) –

Previously married 2.1 (43) –

Income level

HKD 10 000 20.8 (389) –

HKD 10 000 – 30 000 46.6 (869) –

HKD 30 000 – 60 000 22.3 (416) –

HKD 60 000 10.3 (192) –

* Data from Hong Kong Census and Statistics Department,

2008.

804 Aliment Pharmacol Ther 2012; 36: 800-810ª 2012 Blackwell Publishing Ltd

A. D. P. Mak et al.


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factors independently associated with dyspepsia, Chi-

squared tests were used in the whole sample to explore

the association of the psychiatric diagnoses and sociode-

mographic variables with dyspepsia. All diagnostic and

sociodemographic variables were then entered into logis-

tic regression (enter mode, without any elimination) with

dyspepsia. Multivariate analysis did not proceed in the

dyspepsia sub-group due to insuf cient sample size.

Logistic regression and ordinal regression were used to

examine factors independently associated with high

investigation expenditure [arbitrarily dened as spending

HKD50000 (equivalent to USD6427) or more on investi-

gations over the previous 5 years], frequent medical con-

sultations (arbitrarily dened as monthly or more

frequent medical consultations) and their respective asso-

ciation with all diagnostic and sociodemographic vari-

ables. Statistical analyses were performed using the

Statistical Package for Social Studies, Version 16.0 (SPSS

Inc., Chicago, IL, USA). All P values were two-tailedwith the level of statistical signicance specied at 0.05.

RESULTS

Prevalence and sociodemographic prole

Of the 2011 respondents, 8.0% (n = 161) currently ful-

lled Rome III criteria for dyspepsia. Among these

respondents, 81.3% (n = 131) had postprandial distress

syndrome (PDS), 7.5% (n = 12) had epigastric pain syn-

drome (EPS), 4.3% (n = 7) had both PDS and EPS,

while 14.9% (n = 24) was unclassied (Table 5). Allthese subjects reported dyspeptic symptoms that were

occurring more than once a week with onset at least

6 months ago. Amongst all sociodemographic variables,

only lower levels of education were signicantly associ-

ated with dyspepsia. There was also a nonsignicant

trend of high prevalence of dyspepsia in female.

(Table 4).

The 12-month prevalence of GAD was 3.8% (n = 77).

The 12-month prevalence of MDE, at 12.4% (n = 249),

has been reported before.28

Comorbidities of dyspepsia

Dyspepsia was signicantly associated with both GAD

and MDE; 21.3% of respondents with MDE met Rome

III criteria for dyspepsia vs. 6.1% of non-MDE respon-

dents (P < 0.001). 32.9% of dyspeptic respondents vs.

10.6% of nondyspeptic respondents met criteria for

MDE (P < 0.001) (Table 6).

In all 24.3% of GAD respondents had dyspepsia vs.

7.3% of non-GAD respondents (P < 0.001); 11.8% of

dyspepsia respondents also had GAD, vs. 3.1% of non-

dyspepsia respondents (P < 0.001) (Table 6).

In the multivariate analysis that included all sociodemo-

graphic correlates, the adjusted odds ratio of GAD being associated with dyspepsia was 2.03 (95% CI: 1.06 – 3.89,

P = 0.03), while the adjusted OR of MDE being associated

with dyspepsia was 3.56 (95% CI: 2.33 – 5.43, P < 0.001).

Comorbidities of PDS and EPS

Generalised anxiety disorder was found in 10.6%

(n = 14) of PDS [vs. 3.4% (n = 63) non-PDS, P < 0.001]

respondents and 16.7% (n = 2) of EPS [vs. 3.8%

(n = 75) non-EPS] respondents. MDE was found in

34.4% (n = 45) of PDS respondents [vs. 10.9% (n = 204)

non-EPS] and 25% (n = 3) of EPS [vs. 12.3% (n = 246)non-EPS] respondents.

Concomitant MDE and GAD

Having concomitant MDE and GAD was associated with

higher prevalence of comorbid dyspepsia than having

only one or none psychiatric diagnosis; 28.3% (n = 15)

of respondents with both GAD and MDE had dyspepsia

(P < 0.001), vs. 19.2% (n = 42) with a single psychiatric

diagnosis (P < 0.001), and 6.0% (n = 104) in those with-

out psychiatric comorbidity. On multivariate analysis,

having both GAD and MDE was signicantly associatedwith higher prevalence of dyspepsia (Adjusted

OR = 6.65, 95% CI: 3.35 – 13.21, P < 0.001) than having

one psychiatric diagnosis (Adjusted OR = 3.62, 95% CI:

2.37 – 5.51, P < 0.001) and no psychiatric comorbidity.

Chronological relationship in the onset time of

dyspepsia, GAD and MDE

In all, 28.6% of respondents with dyspepsia reported rst

onset of dyspeptic symptoms before age of 20. Current

Table 5 | Prevalence of dyspepsia and its subgroups,

GAD and MDE

Prevalence,

% (n)

Dyspepsia (Rome III) 8.0 (161)

Postprandial distress syndrome 81.3 (131)

Epigastric pain syndrome 7.5 (12)Psychiatric diagnoses

Generalised anxiety disorder 3.8 (77)

Major depressive episode 12.4 (249)

Number of psychiatric diagnoses

No psychiatric diagnosis 86.5 (1739)

One psychiatric diagnosis (GAD OR MDE) 10.9 (219)

Two psychiatric diagnoses (GAD and MDE) 2.6 (53)




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comorbidity with GAD was not signicantly associatedwith early onset of dyspeptic symptoms (33.3% dyspeptic

respondents with comorbid GAD vs. 31.3% without co-

morbid GAD, P = 1.0), nor was MDE comorbidity

(31.4% MDE-comorbid vs. 31.9% non-MDE-comorbid

dyspeptic respondents, P = 1.0).

For respondents with dyspepsia and MDE, 44.5%

reported concomitant onset of the two disorders, 31.5%

reported earlier onset of depression than dyspepsia, while

24% reported onset of dyspepsia before depression. For

GAD-dyspepsia comorbid respondents, up to half (54%)of the respondents reported concomitant onset of the

disorders, while 26.7% reported having dyspepsia rst,

19.3% having GAD rst. The vast majority (89.4%) of

those with both GAD and MDE reported concomitant

onset of GAD and MDE, while 7.8% and 2.8% of those

had GAD and MDE rst respectively.

To further examine the effect of order of onset of dys-

pepsia and mental disorders on occurrence of dyspepsia,

prevalence of dyspepsia was compared between subjects

Table 6 | Sociodemographic characteristics and psychiatric comorbidity in dyspeptic respondents

Dyspepsia

(n = 161), % (n) Crude OR P Adjusted OR P

Gender

Male 6.9 (75) 1 1

Female 8.9 (86) 1.32 (0.95 – 1.83) 0.10 1.16 (0.78 – 1.80) 0.47

Age 0.6215 – 24 7.9 (27) 0.90 (0.51 – 1.56) 0.70 1.04 (0.36 – 3.02) 0.95

25 – 34 7.1 (29) 0.79 (0.46 – 1.37) 0.40 0.90 (0.43 – 1.88) 0.77

35 – 44 6.8 (31) 0.78 (0.46 – 1.34) 0.37 0.78 (0.40 – 1.53) 0.47

45 – 54 9.6 (47) 1.12 (0.68 – 1.84) 0.65 1.18 (0.64 – 2.18) 0.60

55 – 65 8.5 (27) 1 – 1 –

Education 0.27

Primary or below 10.2 (23) 1.87 (1.09 – 3.19) 0.02* 1.51 (0.72 – 3.12) 0.27

Secondary 9.1 (82) 1.61 (1.09 – 2.40) 0.02* 1.58 (0.99 – 2.53) 0.06

Pre college 7.2 (15) 1.24 (0.67 – 2.31) 0.50 1.08 (0.54 – 2.15) 0.83

College or above 5.8 (39) 1 – 1 –

Work status 0.89

Employed 7.6 (92) 0.74 (0.47 – 1.15) 0.18 0.88 (0.51 – 1.53) 0.27

Unemployed 8.5 (11) 0.85 (0.41 – 1.76) 0.66 0.87 (0.39 – 1.95) 0.74

Retired 5.7 (8) 0.55 (0.25 –

1.24) 0.15 0.60 (0.23 –

1.60) 0.31Student 7.9 (19) 0.77 (0.42 – 1.41) 0.39 0.82 (0.28 – 2.39) 0.72

Homemaker 10.1 (28) 1 – 1 –

Marital status 0.94

Single 7.5 (58) 1 – 1 –

Married/living together 8 (95) 1.08 (0.77 – 1.52) 0.66 0.95 (0.57 – 1.60) 0.85

Previously married 14 (6) 1.93 (0.77 – 4.83) 0.16 1.11 (0.39 – 3.15) 0.85

Income level 0.88

HKD 10 000 9.5 (30.4) 1.44 (0.75 – 2.76) 0.28 0.89 (0.41 – 1.87) 0.73

HKD 10 000 – 30 000 7.9 (69) 1.17 (0.83 – 2.15) 0.62 0.84 (0.43 – 1.65) 0.62

HKD 30 000 – 60 000 6.5 (27) 0.95 (0.48 – 1.88) 0.88 0.75 (0.37 – 1.54) 0.44

HKD 60 000 6.8 (13) 1 – 1 –

Psychiatric diagnoses

GAD

No GAD

24.3 (19)

7.3 (142)

4.10 (2.37 – 7.08)


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with onset of mental disorders (GAD or MDE) preced-

ing dyspepsia (To allow comparison, this group also

comprised those with only mental disorders now, based

on the assumption of future onset of dyspepsia) and

those where onset of mental disorders did not precede

dyspepsia. Dyspepsia was not more common in those

with mental disorders preceding dyspepsia (7.7%) com-

pared with those where mental disorders did not precede

dyspepsia (8.0%, P = 0.87). On multivariate analysis that

included all other sociodemographic factors, the associa-

tion of precedent-onset mental disorders with dyspepsia

remained insignicant (Adjusted OR = 0.83 95% CI:

0.47 – 1.45, P = 0.51).

Frequent medical consultations

Frequent medical consultations were, on univariate analy-

sis, less common amongst male (M 10.9% vs. F 17.3%,

P < 0.001) and students. It was more common amongst

homemakers (Employed 14.9%, unemployed 14.1%,retired 17.1%, students 5%, homemakers 18.8%; P = 0.04).

Respondents with dyspepsia made signicantly more

frequent medical consultations than those with no dys-

pepsia (31.7% vs. 12.8%, P < 0.001). GAD and MDE

were also associated with more frequent medical consul-

tations (36.8% GAD vs. 13.5% non-GAD, P < 0.001;

30.4% MDE vs. 12.1% non-MDE, P < 0.001). Using

multivariate analysis, dyspepsia (Adjusted OR = 2.48,

95% CI: 1.65 – 3.72 P < 0.001), MDE (Adjusted

OR = 2.39, 95% CI: 1.64 – 3.46, P < 0.001), female gender

(Adjusted OR = 1.65, 95% CI: 1.21 –

2.23, P < 0.001)were all found to be independent predictors of frequent

medical consultations.

High investigation expenditure

In all, 14% of dyspeptic respondents vs. 9.4% of nondys-

peptic respondents spent moderately [dened as more

than HKD10000 (equivalent to USD 1289) on medical

investigations over the past 5 years]. 3.2% dyspeptic vs.

1.3% nondyspeptic respondents had high investigation

expenditure [dened as spending more than hkd 50 000

(equivalent to USD 6449) on medical investigations overthe past 5 years]. There was a statistically nonsignicant

trend of dyspepsia being associated with high investiga-

tion expenditure (P = 0.06). GAD (5.6% vs. 1.3%,

P = 0.003), but not MDE (2.5% vs. 1.3%, P = 0.16),

was associated with high investigation expenditure on

univariate analysis. GAD was the only signicant

predictor of high investigation expenditure on multivari-

ate analysis (Adjusted OR = 4.65, 95% CI: 1.15 – 18.70,

P = 0.03).

DISCUSSION

We set out to determine the current prevalence of

dyspepsia with stringent Rome III symptom criteria in a

random, representative Chinese community sample.

Participation rate was comparable to previous telephone

health surveys.26 We observed that dyspepsia was

strongly associated and often had coincident onset with

GAD and MDE in the community.

Direct comparisons for community prevalence of

Rome III dyspepsia are sparse. Our conservative gure

was, possible cross-national variation aside, consistent

with the Rome III restrictiveness.3 Omission of the

6-month onset requirement from Rome III criteria may

explain the high prevalence of 20% in the Kalixanda

study.15 We found dyspepsia slightly more common in

females, as in local and overseas data.14, 15 Our GAD

prevalence and sociodemographic correlates were consis-

tent with extant community data, which were also

similar to Western ndings and a previous identically designed survey in Hong Kong.26 The 12.4% MDE

prevalence, reported previously, was higher than the

2007 gure of 8.5%, probably related to the 2008 global

nancial crisis.28

We found signicant and independent association of

dyspepsia with GAD and MDE as mental disorders. This

is consistent with the reported association of anxiety

symptoms with dyspepsia.4, 15 The link with depression

is more controversial. While we found a strong associa-

tion between MDE and dyspepsia, even higher than that

for GAD, the Kalixanda study found anxiety but notdepression to be associated with dyspepsia.15 This may

be due to the inclusion of dyspepsia of shorter duration

in the Kalixanda study, which may have a weaker associ-

ation with depression than anxiety. In addition, the

HADS depression subscale comprises only symptom

scores over 1 week ’s duration and had no requirement

for functional impairment, and therefore it was substan-

tially less accurate than DSM-IV-TR MDE, which

required 2 weeks of depressive symptoms causing signi-

cant functional impairment or marked distress (Table 3).

Nonetheless, signicant association between dyspepsiaand depressive symptoms was noted in a previous local

community survey using HADS and Rome II,14 as well

as a meta-analysis.4 Future surveys on psychiatric com-

orbidity using standard diagnostic assessment will help

clarify the relationship between dyspepsia and depres-

sion.

GAD and MDE were both more common in PDS,

while only GAD was signicantly more common in EPS.

In view of the small sample size, between-group




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comparison would not be meaningful and as such should

be examined in larger community samples.

Particularly salient was the nding that GAD and MDE,

as mental disorders each having distinct biological and

environmental aetiologies, were associated with dyspepsia.

While cross-sectional studies map chronology poorly, our

preliminary ndings were that most of the comorbid sub-

jects had coincident onset of mental disorders and dyspep-

sia, and that preceding mental disorders were not a

signicant risk factor for dyspepsia. Coincident-onset thus

appears to be the predominant mode of comorbidity. This

disputes the assertion of distress from dyspepsia itself

totally explaining its association with depressive and anxi-

ety features. It is also against the view of mental disorders

‘causing ’ dyspepsia. Rather, the nding is consistent with

neurophysiological ndings that autonomic nervous sys-

tem and hypothalamo-pituitary-adrenal axis derange-

ments typical of anxiety disorders and depressive

disorders29 may alter gastrointestinal function.30 It alsoconcurs with evidence that onset of dyspeptic symptoms

‘behaves’ similarly as anxiety and depressive disorders as

systemic reactions to major stressful life events.31 This

strong association between dyspepsia, GAD and MDE

implies that mental disorders should be routinely screened

during the assessment of patients with dyspepsia.

The stepwise increase in risk of dyspepsia with

increased number of psychiatric diagnoses mirrors

evidence from the psychosomatic literature that supports

a dose-response link between somatic symptom load and

psychopathology.32 Studies with larger samples anddetailed severity measures should conrm whether

dyspeptic symptoms could predict level of psychiatric

morbidity in a proportionate manner. Methodologically,

this stresses the value of including both anxiety and

depressive disorders when studying psychiatric comor-

bidity of medical disorders.

Psychiatric comorbidity seemed to have a complex

impact on healthcare use. In this study, dyspepsia and

MDE independently predicted frequent medical consulta-

tions while GAD predicted high investigation expendi-

ture. The extent of somatic symptoms is unlikely toexplain the difference, as patients with both GAD and

MDE are associated with frequent physical complaints

that would drive healthcare use.32 Variances in doctor-

patient interaction and cognitive factors may be other

explanations. In particular, more than 70% of GAD

sufferers have excessive health anxiety,33 which may

drive medical decisions into ordering more investiga-

tions. For MDE, medical consultations may be driven by

the distinct distress and impairment in depression, and

increased mental health literacy of patients regarding

depression as an illness.

Our study has several limitations. First, endoscopy was

not done. It is uncertain how strictly applied Rome III

dyspepsia symptom criteria would predict lack of orga-

nicity. However, the subgroup of subjects with peptic

ulcer disease and gastric ulcer is likely to be a small

minority. Our previous endoscopy study in referred

patients with dyspepsia found organicity in less than 10%

of patients.34 The Kalixanda study found no organicity in

77% of uninvestigated dyspepsia cases,15 while a meta-

analysis found positive endoscopy in 20% of dyspeptics,

only 6% in Rome-dened dyspeptics.35 Second, we did a

brief telephone survey instead of a detailed face-to-face

one. However, by avoiding face-to-face contact, telephone

surveys may avoid psychiatric stigma, and facilitate dis-

closure of sensitive information.36 This is critical for the

Chinese for whom disclosing psychological distress may

be culturally inhibited.37 Third, other potentially impor-tant factors associated with dyspepsia were omitted owing

to the need for brevity in a telephone survey, such as

medication use. Fourth, recall bias and cross-sectional

design limited the study of chronology. In particular, our

analysis on order of onset and prevalence of dyspepsia

had a clear limitation in assuming future onset of

dyspepsia for those with only mental disorders cur-

rently, but such ‘comorbidity ’ was not inevitable. The

order of onset thus designated was limited by this

assumption and any implications on causality need to

be studied more rigorously in future prospective com-munity studies. Fifth, the study was underpowered for

multivariate analysis for variables associated with psy-

chiatric comorbidity and healthcare utilisation in the

dyspepsia subgroup. Future population-based studies

using larger samples may endeavour to explore this

area. Lastly, we assessed current prevalence of dyspepsia

and 12-month prevalence of GAD and MDE so as to

render the ndings comparable to other community

surveys. It should be noted that this approach may

somewhat inate the prevalence gures for the mental

disorders relative to that of dyspepsia.In conclusion, we found Rome III dyspepsia to be

common and strongly associated with MDE and GAD as

mental disorders, with substantial impact on healthcare

use in the community. The implications are that one,

mental disorders should be routinely screened in assess-

ing dyspepsia, especially those exhibiting high levels of

healthcare use. Two, clinicians treating dyspepsia with

comorbid GAD or MDE should regard help-seeking

behaviour as a salient part of illness experience. Instead


A. D. P. Mak et al.


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of routinely discouraging unnecessary consultations or

investigations, holistic and effective approaches in treat-

ing these complexly ill individuals may do their health

better while reducing unnecessary expenses. Collabora-

tive psychosomatic care involving gastroenterologists and

mental health professionals may address this. Lastly, pro-

spective research is needed on courses of dyspepsia and

comorbid mental disorders, as well as translational

research in such light.

ACKNOWLEDGEMENTS

Declaration of personal interests: Dr Arthur Mak is sup-

ported by an educational grant of Pzer Pharmaceutical.

Dr Justin Wu is supported by research funds of Depart-

ment of Medicine & Therapeutics and educational grant

of Pzer Pharmaceutical. Dr Sing Lee received educa-

tional grants on mental health education from Pzer

Pharmaceuticals, GlaxoSmithkline, Wyeth Pharmaceuti-

cals and Johnson & Johnson Pharmaceuticals. Declara-

tion of funding interests: None.

SUPPORTING INFORMATION

Additional Supporting Information may be found in theonline version of this article:

Appendix S1. Comparison of study sample composi-

tion and 2008 Hong Kong Census population data, and

weighting factor applied.

Please note: Wiley-Blackwell are not responsible for

the content or functionality of any supporting materials

supplied by the authors. Any queries (other than missing

material) should be directed to the corresponding author

for the article.

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