Supplementary Table 1. Studies comparing levels of psychopathology between functional dyspepsia patients and healthy controls

Study / Type of study / Population / Control group(s) / Psychological factor(s) / Results
Koloski et al.S1 / Longitudinal (12 year follow-up) / -general population
-total n=1,775 (baseline) →
n=1,002 (follow-up) / not applicable / - anxiety
- depression / -depression baseline → dyspepsia follow-up
-anxiety baseline → dyspepsia follow-up (trend)
Piacentino et al. S2 / Cross-sectional / - IBS with FD (Rome III)
- tertiary care
- n=26 / IBS without FD
(n=56) / psychological distress (SCL-90-R) (9 subscales) / IBS + FD > IBS - FD on 8 subscales
Hartono et al.S3 / Case–control / - FD (Rome III)
- tertiary care
- n=62 / healthy / - anxiety
- depression / - anxiety: 44% FD > 15% healthy
- depression: 23% FD > 7% healthy
Sattar et al.S4 / Case–control / - FD
- tertiary care
- n=150 / healthy / ‘common mental disorders’ / 71% FD > 15% controls
Lee et al.S5 / Cross-sectional / - FD (Rome III)
- tertiary care
- n=70 / healthy (n=127) / depression / FD > controls
De la Roca-Chiapas et al.S6 / Case–control / - FD (Rome II)
- secondary care
- n=15 / healthy / - stress
- anxiety
- depression / FD > controls
Gathaiya et al.S7 / Cross-sectional / - general population
- total n=659
- dyspepsia n=133 (20%) / no dyspepsia / - somatization
- sleep dysfunction / dyspepsia > controls
Aro et al.S8 / Cross-sectional / - general population
- total n=1,001
- FD n=157 (16%) (Rome III) / no FD / - anxiety
- depression / - anxiety: FD > controls
- depression: FD = controls
Ochi et al.S9 / Cross-sectional / - FD (Rome III)
- tertiary care
- n=168 / healthy (n=130) / perfectionism (6 subscales) / - parental criticism: FD > healthy
- other subscales: FD = healthy
Tominaga et al.S10 / Cross-sectional / - FD (Rome II)
- n=96 / - healthy (n=50) / - anxiety
- depression / - anxiety: FD > healthy
- depression: 28% FD > 11% healthy
Pajala at al.S11 / Cross-sectional / - FD
- primary care
- n=205 / - general population (n=1,552) / mental distress / 38% FD > 15% general population
Koloski et al.S12 / Cross-sectional / - FD (Rome I)
- general population
- n=51 / healthy (n=100) / Abuse / - adulthood physical or emotional abuse: FD > healthy
- other abuse: FD = healthy
Jones et al.S13 / Cross-sectional / - FD (Rome II)
- primary/ secondary care
- n=151 / healthy (n=90) / psychological distress (SCL-90-R) (9 subscales) / FD > healthy on all subscales
Castillo et al.S14 / Cross-sectional / - dyspepsia
- general population
- n=35 / no dyspepsia (n=17) / Somatization / dyspepsia > controls
Jones et al.S15 / Cross-sectional / - FD (Rome II)
- tertiary care
- n=111 / healthy (n=53) / - somato-sensory amplification
- alexithymia / FD > healthy
Locke et al.S16 / Case–control / - FD (Rome II)
- general population
- n=47 / healthy (n=119) / psychological distress(SCL-90-R)(9 subscales) / FD > healthy on 8 subscales
Henningsen et al.S17 / Meta-analysis / FD / healthy / - anxiety (n=871)
- depression (n=3138) / FD > healthy
Malt et al.S18,S19 / Cross-sectional / - FD
- tertiary care
- n=18 / healthy (n=49) / Study 1: speech content analysis65
- anxiety (7 subscales)
- depression (8 subscales)
- hostility (5 subscales)
- hope
- cognitive impairment
Study 266
psychiatric disorders (current & lifetime)
*INTERVIEW* / Study 1: speech content analysis
- death anxiety: FD > healthy
- all other: FD = healthy
Study 2
- mood disorders: FD > healthy
- anxiety disorders: FD = healthy
Li et al.S20 / Cross-sectional / - dyspepsia
- general population
- total n=1016
- dyspepsia n=239 (24%) / no dyspepsia / anxiety or depression / dyspepsia (16%) > no dyspepsia (7%)
Lee et al.S21 / Case–control / - FD
- tertiary care
- n=30 / healthy with unexplained fatigue / - psychological distress (SCL-90-R) (9 subscales)
- perceived stress
- coping (5 subscales) / - psychological distress: D > control 5 subscales
- perceived stress: FD > control
- coping: FD < control 3 subscales
Cheng et al.S22 / Case–control / - FD
- secondary care
- n=30 / healthy / - coping (8 subscales)
- appraisal of stressful life events (3 ratings)
*INTERVIEW* / - coping: FD < healthy 5 subscales
- controllability stressful life events: FD < healthy
Norton et al.S23 / Cross-sectional / - FD (Rome I)
- university students
- total n=127
- FD n=29 / no FD / - anxiety sensitivity
- anxiety
- depression / - anxiety sensitivity: FD > no FD
- anxiety, depression: FD = no FD
Herschbach et al.S24 / Cross-sectional / - general population
- total n=2,201
- dyspepsia n=240 / no dyspepsia / - depression
- somatization
- neuroticism
- hypochon-driasis
- stressful life events
- social support / FD > no dyspepsia
Haug et al.S25 / Case–control / - FD
- tertiary care
- n=100 / Healthy / - anxiety
- depression
- neuroticism
- stressful life events
*INTERVIEW* / FD > healthy
Jain et al.S26 / Cross-sectional / - FD
- tertiary care
- n=35 / healthy (n=45) / - neuroticism
- somatization
- psychiatric disorders
- stressful life events / - neuroticism, somatization FD > healthy
- psychiatric disorders: FD > healthy
- stressful life events: FD = healthy
Jonsson et al.S27 / Case–control / - FD (chronic)
- tertiary care
-n=25 / healthy / - psychological distress (SCL-90)(9 subscales)
- psychiatric disorders
- social support
- perceived distress
- personality (15 subscales) / - SCL-90: FD > healthy somatization only
- psychiatric disorders: FD > healthy
- social support: FD = healthy
- perceived distress: FD > healthy
- personality: FD > controls detachment only
Haug et al.S28 / Case–control / - FD
- tertiary care
- n=100 / healthy / - anxiety
- depression
- neuroticism
- locus of control
- dysfunctional attitudes
*INTERVIEW* / - anxiety, depression, neuroticism: FD > healthy
- locus of control, dysfunctional attitudes: FD = healthy
Hui et al.S29 / Case–control / - FD
- consulters
- n=33 / healthy / - major stressful life events
- daily stressful events / - number of major stressful life events: FD = healthy
- perceived magnitude of major stressful life events: FD > healthy
- daily stressful events: FD = healthy
Bennett et al.S30 / Case–control / - FD
- tertiary care
- n=62 / healthy / - anxiety
- depression
- neuroticism
- coping
- life events
- social support
*INTERVIEW* / FD > healthy
Talley et al.S31 / Cross-sectional / - FD
- tertiary care
- n=31 / healthy (n=128) / - personality & psycho-pathology (11 subscales) / - FD > healthy on 5 subscales
- FD = organic gastrointestinal disease on all subscales
Kok et al.S32 / Case–control / - FD
- consulters
- n=23 / healthy relatives of psychiatric outpatients / - depression
- psychiatric disorders
- personality
- hostility / - depression: FD > controls
- psychiatric disorders: 22% FD > 4% controls
- personality, hostility: FD = controls
Talley et al.S33 / Case–control / - FD
- secondary/ tertiary care
- n=109 / healthy / socioeconomic factors / FD = healthy
Talley et al.S34 / Case–control / - FD
- secondary/ tertiary care
- n=82 / healthy / emotional control / FD = healthy
Talley et al.S35 / Case–control / - FD
- secondary/ tertiary care
- n=76 / healthy / - anxiety
- depression
- neuroticism / FD > healthy
Talley et al.S36 / Case–control / - FD
- secondary/ tertiary care
- n=68 / healthy / life events
- number
- distress score / FD = healthy
Population-based studies are indicated in italics. *INTERVIEW* - these studies used a (semi-structured) psychiatric interview rather than self-report rating scales to assess psychosocial factors or psychiatric co-morbidity. Abbreviations: FD, functional dyspepsia; SCL-90(-R), symptom checklist-90 (revised).

S1.Koloski, N.A. etal. The brain-gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut61, 1284–1290 (2012).

S2.Piacentino, D. etal. Psychopathological features of irritable bowel syndrome patients with and without functional dyspepsia: a cross sectional study. BMC Gastroenterol.11, 94 (2011).

S3.Hartono, J.L., Mahadeva, S. & Goh, K.L. Anxiety and depression in various functional gastrointestinal disorders: Do differences exist? J.Dig. Dis. 13, 252–257 (2012).

S4.Sattar, A., Salih, M. & Jafri, W. Burden of common mental disorders in patients with functional dyspepsia. J. Pak. Med. Assoc.60, 995–997 (2010).

S5.Lee, H.J. etal. Depressive mood and quality of life in functional gastrointestinal disorders: differences between functional dyspepsia, irritable bowel syndrome and overlap syndrome. Gen. Hosp. Psychiatry32, 499–502 (2010).

S6.De la Roca-Chiapas, J.M. etal. Stress profile, coping style, anxiety, depression, and gastric emptying as predictors of functional dyspepsia: A case-control study. J. Psychosom. Res.68, 73–81 (2010).

S7.Gathaiya, N. etal. Novel associations with dyspepsia: a community-based study of familialaggregation, sleep dysfunction and somatization.Neurogastroenterol. Motil.21, 922–e69 (2009).

S8.Aro, P. etal. Associations with uninvestigated and functional dyspepsia (Rome III) in arandom adult population: The Kalixanda study.Gastroenterology137, 94–100 (2009).

S9.Ochi, M. etal. Perfectionism underlying psychological background correlated with thesymptoms of functional dyspepsia. J. Gastroenterol. 43, 699–704 (2008).

S10.Tominaga, K. etal. Comparison of gastrointestinal symptoms and psychological factors offunctional dyspepsia to peptic ulcer or panic disorderpatients. Inflammopharmacology15, 84–89 (2007).

S11.Pajala, M., Heikkinen, M. & Hintikka, J. Mental distress in patients with functional or organicdyspepsia: a comparative study with a sample of thegeneral population. Aliment. Pharmacol. Ther.21, 277–281 (2005).

S12.Koloski, N.A., Talley, N.J. & Boyce, P.M. A history of abuse in community subjects with irritable bowel syndrome and functional dyspepsia: the roleof other psychosocial variables. Digestion72, 86–96 (2005).

S13.Jones, M.P., Sharp, L.K. & Crowell, M.D. Psychosocial correlates of symptoms in functionaldyspepsia. Clin. Gastroenterol. Hepatol.3,521–528 (2005).

S14.Castillo, E.J. etal. A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia. Clin. Gastroenterol. Hepatol.2, 985–996 (2004).

S15.Jones, M.P., Schettler, A., Olden, K. & Crowell, M.D. Alexithymia and somatosensory amplification in functional dyspepsia. Psychosomatics45, 508–516 (2004).

S16.Locke, G. R. 3rd, Weaver, A.L., Melton, J. L. 3rd, & Talley, N.J. Psychosocial factors are linked tofunctional gastrointestinal disorders: apopulation based nested case–control study.Am. J. Gastroenterol.99, 350–357 (2004).

S17.Henningsen, P., Zimmermann, T. & Sattel, H. Medically unexplained physical symptoms, anxiety, and depression: ameta-analytic review.Psychosom. Med.65, 528–533(2003).

S18.Malt, E.A. & Ursin, H. Mutilation anxiety differs among females with fibromyalgia and functional dyspepsia and population controls. J. Psychosom. Res.54, 523–531 (2003).

S19.Malt, E.A., Berle, J.E., Olafsson, S., Lund, A. & Ursin, H. Fibromyalgia is associated with panic disorder and functional dyspepsia with mood disorders: a study of women with random sample population controls. J. Psychosom. Res.49, 285–289 (2000).

S20.Li, Y., Nie, Y., Sha, W. & Su, H. The link between psychosocial factors and functional dyspepsia: an epidemiological study. Chin.Med.J. (Engl.)115,1082–1084 (2002).

S21.Lee, S.Y. etal. Stress, coping, and depression in non-ulcer dyspepsia patients. J. Psychosom. Res.49, 93–99 (2000).

S22.Cheng, C., Hui, W. M. & Lam, S. K. Coping style of individuals with functional dyspepsia. Psychosom. Med.61, 789–795 (1999).

S23.Norton, G.R., Norton, P.J., Asmundson, G.J.G., Thompson, L.A. & Larsen, D.K. Neurotic butterflies in my stomach: The role of anxiety, anxiety sensitivity and depression in functional gastrointestinal disorders. J. Psychosom. Res.47, 233–240 (1999).

S24.Herschbach, P., Henrich, G. & von Rad, M. Psychological factors in functional gastrointestinal disorders: characteristics of the disorder or of the illness behavior? Psychosom. Med.61, 148–153 (1999).

S25.Haug, T.T., Wilhelmsen, I., Berstad, A. & Ursin, H. Life events and stress in patients with functional dyspepsia compared with patients with duodenalulcer and healthy controls. Scand. J. Gastroenterol.30, 524–530 (1995).

S26.Jain, A.K., Gupta, J.P., Gupta, S., Rao, K.P. & Bahre, P.B. Neuroticism and stressful life events in patients with non-ulcer dyspepsia. J. Assoc. Physicians India43, 90–91 (1995).

S27.Jonsson, B.H., Theorell, T. R. & Gotthard, R. Symptoms and personality in patients with chronic functional dyspepsia. J. Psychosom. Res. 39, 93–102 (1995).

S28.Haug, T.T., Svebak, S., Wilhelmsen, I., Berstad, A. & Ursin, H. Psychological factors and somatic symptoms in functional dyspepsia. A comparison withduodenal ulcer and healthy controls. J. Psychosom. Res.38, 281–291 (1994).

S29.Hui, W.M., Shiu, L.P. & Lam, S.K. The perception of life events and daily stress in nonulcer dyspepsia. Am. J. Gastroenterol.86, 292–296(1991).

S30.Bennett, E., Beaurepaire, J., Langeluddecke, P., Kellow, J. & Tennant, C. Life stress and non-ulcer dyspepsia: a case–control study. J. Psychosom. Res.35, 579–590 (1991).

S31.Kok, L.P., Yap, I.L. & Guan, R.Y. Psychosocial aspects of non-ulcer dyspepsia. Singapore Med. J.30, 346–349 (1989).

S32.Talley, N.J. etal. Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome. Gastroenterology99, 327–333(1990).

S33.Talley, N.J., Jones, M. & Piper, D.W. Psychosocial and childhood factors in essential dyspepsia. A case-control study. Scand. J. Gastroenterol.23, 341–346 (1988).

S34.Talley, N.J., Ellard, K., Jones, M., Tennant, C. & Piper, D.W. Suppression of emotions in essential dyspepsia and chronic duodenal ulcer. A case-controlstudy. Scand. J. Gastroenterol.23, 337–340 (1988).

S35.Talley, N.J., Fung, L.H., Gilligan, I.J., McNeil, D. & Piper, D.W. Association of anxiety, neuroticism, and depression with dyspepsia of unknown cause. Acase-control study. Gastroenterology90, 886–892 (1986).

S36.Talley, N.J. & Piper, D.W. Major life event stress and dyspepsia of unknown cause: a case control study. Gut27, 127–134 (1986).

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