The Importance of Hypochondriasis in Dyspeptic Patients

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1 American Journal of Psychology and Behavioral Sciences 2018; 5(1): ISSN: (Print); ISSN: (Online) The Importance of Hypochondriasis in Dyspeptic Patients Michel Bouchoucha 1, 2, *, Maria Hejnar 3, Pierre Rompteaux 2, Gheorghe Airinei 2, Florence Mary 2, Robert Benamouzig 2 1 Department of Physiology, Université Paris V René Descartes, Paris, France 2 Service de Gastroentérologie, Hôpital Avicenne, Bobigny, France 3 Service de Psychiatrie et de psychopathologie, Hôpital Avicenne, Bobigny, France address * Corresponding author To cite this article Michel Bouchoucha, Maria Hejnar, Pierre Rompteaux, Gheorghe Airinei, Florence Mary, Robert Benamouzig. The Importance of Hypochondriasis in Dyspeptic Patients. American Journal of Psychology and Behavioral Sciences. Vol. 5, No. 1, 2018, pp Received: March 5, 2018; Accepted: March 22, 2018; Published: April 27, 2018 Abstract Psychological factors are involved in functional dyspepsia and irritable bowel syndrome. The aim of the study was to characterize the psychological factors associated with functional dyspepsia (FD) with or without overlap with irritable bowel syndrome (IBS). We included 693 outpatients (69% female) consulting in a tertiary center for functional gastrointestinal disorders (FGIDs) in this cross sectional study. Patients have filled a MMPI-2 questionnaire and a standard Rome III clinical questionnaire. Data analysis was performed using univariate analysis and multivariate logistic regression. Dyspeptic disorders without IBS were found in 139 patients (20%) (21 had epigastric pain syndrome, 46 postprandial distress syndrome, 72 nonspecific dyspepsia), 214 patients (31%) had overlap between FD and IBS, 68 patients (10%) have only IBS, and 272 (39%) had other FGIDs. These groups show no difference for age, stool form, but patients with overlap between FD and IBS have more frequently female gender (P<0.05) and all dyspeptic patients had lower BMI than patients with other FGIDs. As compared to the group "other FGIDs" patients, the multivariate analysis shows that patients with isolated FD are associated with lower BMI (P=0.002; OR=0.921; 95% CI=[ ]), and higher hypochondriasis scale (P<0.001; OR=1.096; 95% CI=[ ]), patients with overlap of IBS and FD are associated with lower BMI (P=0.001; OR=0.929; 95% CI=[ ]), higher Infrequency scale (P=0.013; OR=1.035; 95% CI=[ ]), higher hypochondriasis scale (P<0.001; OR=1.095; 95% CI=[ ]) and lower schizophrenia scale (P=0.036; OR=0.959; 95% CI=[ ]). To conclude high hypochondriasis scales are found in FD patients and in patients with overlap between IBS and dyspepsia. Keywords Hypochondriasis, Dyspepsia, Irritable Bowel Syndrome, Personality, MMPI, Depression, Anxiety 1. Introduction Dyspepsia without any organic gastrointestinal disease is called functional dyspepsia (FD) [1]. It is a frequent disorder in the general population, and its prevalence could reach 38% as in a Swedish population-based on upper endoscope study [2]. Irritable bowel syndrome (IBS) is also a common disorder in gastroenterology practice and in the community, defined by the presence of chronic or recurring symptoms that include abdominal pain, flatulence, bloating, and altered bowel habits [3]. Although several functional gastrointestinal disorders (FGIDs) may coexist in an individual patient [4], each syndrome can be reliably identified as a distinct and homogeneous entity [5]. Although functional dyspepsia and IBS are considered separate disorders, many subjects report concomitant symptoms representing the same disease entity, the "irritable gut" [6]. The clinical evidence of a change in predominant symptom over time between FD and IBS [6] induces to search for both common pathophysiology and management. However, in IBS patients, sex ratio, frequencies of abnormal transit or defecation disorders, association to FD

2 2 Michel Bouchoucha et al.: The Importance of Hypochondriasis in Dyspeptic Patients vary strongly according to the countries [6, 7]. The biopsychosocial approach, developed by George Engel [8], emphasizes the importance of the association of human health with life events. This approach considers biological, psychological, and social factors and their interactions in understanding health, illness, and health care delivery. It was used to analyze functional gastrointestinal disorders (FGIDs) in the Rome III presentation [5], mainly for the management of IBS patients [9]. According to this hypothesis, FGIDs result from dysregulation of central and enteric nervous system function, which is manifested as dysmotility and/or visceral hypersensitivity, and is modified by psychosocial processes. In these multicausal pathologies, these factors determine the filling of the illness [10, 11]. Previous studies have shown that chronic stressors provoked by psychological and extra-intestinal disturbance are most specific for the functional dyspepsia-ibs group of syndromes [12]. In dyspeptic patients, hypochondriasis [11, 13, 14], anxiety and depression [15-19] are frequently found after psychological evaluation. Nevertheless, most of these studies do not use the Rome criteria [10], and psychological tests are frequently limited to depression and life events [20, 21]. In addition, the MMPI or the MMPI-2 were rarely used to characterize functional dyspepsia or the overlap of IBS and FD as defined by the Rome criteria. The present study aimed to evaluate the psychological profile of dyspeptic patients in a tertiary center by using a normalized psychometric test, the MMPI-2 according to the simultaneous presence of IBS. 2. Patients and Methods 2.1. Subjects Between September 2010 and December 2015, 1655 outpatients were consecutively referred by gastroenterologists to our Center for Functional GI and Motility Disorders (CEFRED, Centre d'exploration Fonctionnelle et de Rééducation Digestive, Gastroenterology Clinic of the Avicenne Hospital), a tertiary center for FGIDs management. A full evaluation failed to yield an organic cause for their complaint. This included morphological evaluation (endoscopy or radiology), serological testing for coeliac disease, lactulose breath test and the ruling out of metabolic, endocrinologic, neurologic etiologies, or other potential organic explanations for their symptoms. In patients with reflux symptoms, 24-hr ph or ph-impedance studies with symptom association were undertaken to rule out non erosive reflux disease before labelling as functional heartburn. None of these patients was using narcotics or had been submitted to any previous surgery of the gastrointestinal tract. A single investigator (MB) confirmed, independently, the validity of the initial diagnosis of FGID. Among these subjects, 693 have filled a MMPI-2 questionnaire and a standard Rome III clinical questionnaire. These patients (69% female), aged 45.1±16.5 years (M ± SD), (BMI 26.0±4.9 kg/m²) were included in the present study. The patients were divided into four groups according to the Rome III questionnaire and the overlap of GI disorders: functional dyspepsia without IBS, IBS without functional dyspepsia, IBS with functional dyspepsia, and other FGIDs Experimental Procedure The study was declared in the French National Agency for drug safety (ANSM, Agence Nationale de Sécurité du Médicament et des produits de santé, decision number: A ), and performed in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) and the standards established by the author's Institutional Review Board Study Design The comparison of the groups of FGID patients was performed by using a cross sectional study Clinical Questionnaires Patients in the gastroenterologist s office accepted to fill out by themselves a standard clinical questionnaire based on diagnostic questions for FGIDs [22]. The interpretation was based on the functional disorders as defined by the Rome III criteria. Functional gastroduodenal disorders as postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), PDS-EPS overlap, belching disorders were diagnosed when there was no evidence for structural disease at upper endoscopy, abnormal behavior (self-induced vomiting, chronic cannabinoid use), central nervous system abnormalities or metabolic diseases that could explain the symptoms [1]. As defined by the Rome III criteria, Irritable bowel syndrome (IBS) was diagnosed when recurrent abdominal pain or discomfort occurred more than 2 days per month in the last 3 months was associated with two or more of the following: i) improvement with defecation, ii) onset associated with a change in frequency of stool or iii) onset associated with a change in form of stool. Subtypes of IBS (IBS with constipation (IBS-C), IBS with diarrhea (IBS- D), mixed IBS (IBS-M) and unsubtyped IBS (IBS-U) were defined according to the Rome III criteria [3]. Other functional bowel disorders (bloating, constipation, diarrhea, and unspecified) were diagnosed when the criteria for a diagnosis of IBS were insufficient or absent. Finally, non-specific bowel disorders were diagnosed by exclusion when patients did not meet the above mentioned criteria. Functional esophageal disorders (heartburn, chest pain of presumed esophageal origin, dysphagia and globus), functional abdominal pain syndrome, and functional anorectal disorders (fecal incontinence, functional ano-rectal pain, including levator ani syndrome proctalgia fugax, and difficult defecation) were diagnosed according to the Rome III criteria [23-25]

3 American Journal of Psychology and Behavioral Sciences 2018; 5(1): Psychological Profiles The French version of the Minnesota Multiphasic Personality Inventory 2 (MMPI-2) was utilized to assess the psychological profile (Éditions du Centre de Psychologie Appliquée, 15 rue Henri Rol-Tanguy, Montreuil France). MMPI-2 is a comprehensive, reliable, and valid measure of personality. The individual raw MMPI-2 score is then converted to a T-scale score (M of 50; SD of 10) which is age and sex-adjusted to the normal controls [26]. For each subject, the MMPI-2 is scored by six validity scales: lie scale, L, (this scale attempts to detect a deliberate attempt of the patient to present himself/herself in a favorable light); F (symptom exaggeration) scale; Fb (Infrequency Back, endorsement of low frequency items on the latter part of the MMPI-2), K scale (test defensiveness, assesses the willingness of the patient to disclose personal information). Moreover, two methods were used to detect inconsistent responses: TRIN (True Response Inconsistency) scale, 23 paired questions that are opposite of each other [27], and VRIN (Variable Response Inconsistency), 49 pairs of semantically inconsistent responses [27]. In addition, 10 clinical scales, including Hypochondriasis (Hs), Depression (D), Hysteria (Hy), Psychopathic deviate (Pd), Masculinity/femininity (Mf), Paranoia (Pa), Psychasthenia (Pt), Schizophrenia (Sc), Hypomania (Ma), and Social introversion (Si) were also recorded. The other scales (15 content scales, 14 supplementary scales and 31 Harris-Lingoes scales) were recorded but not used in the present study because of the low number of subjects in some groups 2.4. Statistical Analysis Statistical analyses were carried out using IBM SPSS (IBM SPSS Statistics v20). The results are expressed as N (%) for qualitative variables, and as are expressed as Mean ± Standard deviation (SD). for quantitative variables. χ² tests were used for analysis of qualitative variables. Categorical differences among the groups were analyzed by a one-way analysis of variance (ANOVA). Multiple comparisons with post hoc tests using Bonferroni correction were used if ANOVA showed significant differences (α level P< 0.05). Whenever multiple tests are employed in a non-experimental paradigm there is an increased risk of type I (false positive) error. Hence, we interpret statistically significant findings in this study as evidence of an association rather than definitive proof of an association. Logistic multinomial regression was used for data analysis that included systematically the clinical group as dependent variables and as independent variables, BMI, age, gender and the MMPI-2 scales, with the non-ibs, non-gastrointestinal disorder used as a reference group. The backwards selection was used for model selection during the multivariate logistic regression. Statistically significant variables (P<0.05) remained in the adjusted model. 3. Results The demographics and clinical results of the present study are summarized in the Table 1. Demographic results The 693 patients included in the study were segregated into four different groups: 139 patients (20%) had dyspeptic disorders without IBS (3%) had epigastric pain syndrome, 46 (7%) had postprandial distress syndrome, 72 (10%) had nonspecific dyspepsia, overlap between postprandial distress syndrome and epigastric pain syndrome --, 214 patients (31%) had overlap between IBS and functional dyspepsia (3%) had IBS and epigastric pain syndrome, 75 (11%) had IBS with postprandial fullness and 109 (16%) had IBS with nonspecific dyspepsia --, 68 (10%) had IBS without functional dyspepsia and 272 (39%) had other FGIDs. These groups show no difference for age, but patients with overlap between functional dyspepsia and IBS have more frequently female gender (P<0.05) and all dyspeptic patients had lower BMI than patients with other FGIDs (P=0.017 for the isolated functional dyspepsia group and P=0.005 for overlap between functional dyspepsia and IBS). Clinical characteristics of the patients with functional dyspepsia, with IBS and with overlap of functional dyspepsia and IBS. As compared with patients with other FGIDS, patients with isolated functional dyspepsia have a higher prevalence of globus (P<0.01), chest pain (P<0.05), heartburn (P<0.01), dysphagia (P<0.01), belching disorders (P<0.05), while patients with IBS have higher prevalence of nonspecific anorectal disorders (P<0.01). Patients with overlap of IBS and functional dyspepsia have higher prevalence of chest pain (P<0.01), heartburn (P<0.01), dysphagia (P<0.01), belching disorders (P<0.01), soiling (P<0.01), levator ani syndrome (P<0.01), proctalgia fugax (P<0.01) and difficult defecation than patients with other FGIDs. In contrast, stool form, assessed by the Bristol stool form, was not different between the four groups of patients. Psychological characteristics of these 4 groups of patients Mean value of clinical MMPI-2 scales is shown in Figure 1; univariate analysis of psychological characteristics of the four groups of patients is summarized in the Table 2. Comparing the 3 groups with the patients without IBS and without functional dyspepsia, we found the following results: i. Patients with isolated functional dyspepsia have higher score for 2 validity scales: Infrequency scale back (Fb) (P=0.037), Infrequency scale (F) (P=0.003) and 5 clinical scales: Depression (D) (P=0.002), Hysteria (Hy) (P<0.001), Paranoia (Pa) (P=0.012), Hypomania (Ma) (P=0.019) and Schizophrenia (Sc) (P=0.010). ii. Patients with isolated IBS have higher score for 6 clinical scales: Hypochondriasis (Hs) (P<0.001), Depression (D) (P=0.010), Hysteria (Hy) (P<0.001), Paranoia (Pa) (P=0.045), Psychasthenia (Pt) (P=0.006) and Schizophrenia (Sc) (P=0.003).

4 4 Michel Bouchoucha et al.: The Importance of Hypochondriasis in Dyspeptic Patients iii. Patients with overlap of IBS and functional dyspepsia have higher score for 3 validity scales: Infrequency scale back (Fb) (P<0.001), Infrequency scale (F) (P<0.001), K scale (K) (P<0.001) and 7 clinical scales: Hypochondriasis (Hs) (P<0.001), Hysteria (Hy) (P<0.001), Psychopathic Deviate (Pd) (P<0.001), Paranoia (Pa) (P<0.001), Psychasthenia (Pt) (P<0.001), Hypomania (Ma) (P=0.001) and Schizophrenia (Sc) (P<0.001). The multivariate analysis shows that the groups of patients have specific psychological characteristics as compared to the group of non-ibs, non-dyspeptic patients: i. Patients with isolated functional dyspepsia are associated with lower BMI (P=0.002; OR=0.921; 95% CI=[ ]), and higher hypochondriasis scale (P<0.001; OR=1.096; 95% CI=[ ]). ii. Patients with overlap of IBS and functional dyspepsia are associated with lower BMI (P=0.001; OR=0.929; 95% CI=[ ]), higher Infrequency scale (F) (P=0.013; OR=1.035; 95% CI=[ ]), higher hypochondriasis scale (P<0.001; OR=1.095; 95% CI=[ ]) and lower schizophrenia scale (P=0.036; OR=0.959; 95% CI=[ ]). iii. In contrast, patients with isolated IBS are not associated with any significant parameter, as compared with other FGIDs patients. Frequency of abnormal psychological scales The frequencies of the abnormal values for validity and clinical scales found in the different groups of patients are summarized in the Table 3. By comparison with the group of patients without functional dyspepsia and without IBS, patients with overlap of IBS and functional dyspepsia have higher frequency of abnormal score for 2 validity scales: Infrequency scale (F, P<0.001) Infrequency scale back (Fb, P<0.01), and 6 clinical scales: Hypochondriasis (Hs, P<0.01), Depression (D, P<0.01), Hysteria (Hy, P<0.01), Paranoia (Pa, P<0.01), Psychasthenia (Pt, P<0.01) and Schizophrenia (Sc, P<0.01). The multivariate logistic analysis shows that, as compared to the group of non-ibs/non-dyspeptic patients: i. Patients with isolated functional dyspepsia are associated with lower BMI (P=0.005; OR=0.931; 95% CI=[ ]), and higher frequency of abnormal hypochondriasis scale (P<0.001; OR=2.790; 95%CI=[ ]). ii. Patients with isolated IBS are associated with higher frequency of abnormal hypochondriasis scale (P=0.007; OR=2.521; 95%CI=[ ]) despite normal mean score (Figure 2) and higher frequency of abnormal hysteria scale (P=0.032; OR=2.534; 95%CI=[ ]), iii. Patients with overlap of IBS and functional dyspepsia are associated with lower BMI (P=0.002; OR=0.934; 95%CI=[ ]), higher frequency of abnormal Infrequency scale (F; P=0.002; OR=3.392; 95%CI=[ ]), higher frequency of abnormal hypochondriasis scale (P<0.001; OR=3.993; 95%CI=[ ]), higher frequency of abnormal Hysteria score (P=0.010; OR=2.270; 95%CI=[ ]) and lower frequency of abnormal Psychopathic deviate scale (P=0.021; OR=0.355; 95%CI=[ ]). Figure 1. MMPI-2 clinical scales of dyspeptic patients and irritable bowel syndrome. Non-dyspeptic-non IBS patients have significant lower MMPI scales than other FGID patients. Patients with IBS and dyspepsia overlap have the highest values. For these scales, normalized for age and gender, normal mean is 50 and standard deviation is 10. Abbreviations: FGIDs: functional gastrointestinal disorders; IBS: Irritable Bowel Syndrome

5 American Journal of Psychology and Behavioral Sciences 2018; 5(1): Figure 2. Odds ratio of Hypochondriasis scales of dyspeptic patients according to the presence of irritable bowel syndrome; the other functional gastrointestinal disorders group being the reference group. Graphical representation of the Odds ratio and their 95% CI of Hypochondriasis MMPI-2 scales in patients with dyspepsia, IBS and overlap of dyspepsia and IBS by comparison with patients with other functional gastrointestinal disorders. Higher odds of hypochondriasis is found in patients with dyspepsia have (OR=1.096; 95% CI= [ ]), and in patients with overlap of dyspepsia and IBS (OR=1.095; 95% CI= [ ]). In contrast, in IBS patients, hypochondriasis was not different from patients without dyspepsia and without IBS (P=0.102; OR=1.032; 95% CI=[ ]). Abbreviations: FGIDs: functional gastrointestinal disorders; IBS: Irritable Bowel Syndrome Table 1. Demographics and clinical description of the population. All patients Isolated Overlap IBS Other FGID Isolated IBS dyspepsia & Dyspepsia patients P value N (%) 693 (100) 139 (20) 68 (10) 214 (31) 272 (39) Age (years) 45.1± ± ± ± ± Female (%) 479 (69) 93 (67) 39 (57) 161 (75) 186 (68) Body Mass Index (kg/m²) 26.0± ± ± ± ± Bristol stool Form scale 3.9± ± ± ± ± Globus 137 (20) 44 (32) 11 (16) 51 (24) 31 (11) <0.001 Esophagus ChestPain 190 (27) 48 (35) 16 (24) 94 (44) 32 (12) <0.001 Heartburn 218 (31) 75 (54) 12 (18) 99 (46) 32 (12) <0.001 Dysphagia 139 (20) 45 (32) 10 (15) 60 (28) 24 (9) <0.001 Gastro- Duodenal Bowel Epigastric pain syndrome 51 (7) 21 (15) 0 (0) 30 (14) 0 (0) <0.001 Postprandial distress syndrome 121 (17) 46 (33) 0 (0) 75 (35) 0 (0) <0.001 Epigastric pain-postprandial distress overlap 183 (26) 74 (53) 0 (0) 109 (51) 0 (0) <0.001 Belching disorders 193 (28) 49 (35) 19 (28) 97 (45) 28 (10) <0.001 All IBS subtypes 282 (41) 0 (0) 68 (100) 214 (100) 0 (0) <0.001 IBS Constipation 92 (13) 0 (0) 19 (28) 73 (34) 0 (0) <0.001 IBS Diarrhea 86 (12) 0 (0) 24 (35) 62 (29) 0 (0) <0.001 IBS Mixed 59 (9) 0 (0) 11 (16) 48 (22) 0 (0) <0.001 IBS Unspecified 45 (6) 0 (0) 14 (21) 31 (14) 0 (0) <0.001 Constipation 99 (14) 40 (29) 0 (0) 0 (0) 59 (22) <0.001 Diarrhea 80 (12) 28 (20) 0 (0) 0 (0) 52 (19) <0.001 Bloating 46 (7) 15 (11) 0 (0) 0 (0) 31 (11) <0.001 Nonspecific 65 (9) 19 (14) 0 (0) 0 (0) 46 (17) <0.001 Abdominal pain 40 (6) 25 (18) 0 (0) 0 (0) 15 (6) <0.001 Fecal incontinence 55 (8) 11 (8) 7 (10) 18 (8) 19 (7) Levator Ani syndrome 40 (6) 8 (6) 3 (4) 25 (12) 4 (1) <0.001 Anorectal Proctaglia Fugax 54 (8) 16 (12) 5 (7) 26 (12) 7 (3) <0.001 Non specific anorectal disorders 41 (6) 7 (5) 13 (19) 13 (6) 8 (3) <0.001 Difficult defecation 249 (36) 44 (32) 32 (47) 116 (54) 57 (21) <0.001 Qualitative variables are expressed as N (%). Quantitative variables are expressed as Mean ± Standard deviation. Abbreviations: IBS: irritable bowel syndrome; FGID: Functional gastrointestinal disorder

6 6 Michel Bouchoucha et al.: The Importance of Hypochondriasis in Dyspeptic Patients Table 2. MMPI-2 validity and clinical scales in the different groups of patients. All patients Isolated dyspepsia Isolated IBS Overlap IBS and Dyspepsia Other FGID patients P value Validity scales L scale 56.9± ± ± ± ± Infrequency scale (F) 59.5± ± ± ± ±13.6 <0.001 Infrequency scale back (Fb) 59.5± ± ± ± ±14.3 <0.001 K scale 48.2± ± ± ± ±10.5 <0.001 TRIN 59.7± ± ± ± ± VRIN 54.6± ± ± ± ± Clinical scales 1 Hypochondriasis (Hs) 67.4± ± ± ± ±12.4 < Depression (D) 62.1± ± ± ± ±11.2 < Hysteria (Hy) 60.9± ± ± ± ±12.0 < Psychopathic Deviate (Pd) 53.8± ± ± ± ±11.6 < Masculinity-Femininity (Mf) 52.9± ± ± ± ± Paranoia (Pa) 56.0± ± ± ± ±12.7 < Psychasthenia (Pt) 57.2± ± ± ± ±11.4 < Schizophrenia (Sc) 57.3± ± ± ± ±12.6 < Hypomania (Ma) 50.8± ± ± ± ±10.3 < Social Introversion (Si) 55.1± ± ± ± ± Abbreviations: IBS: irritable bowel syndrome; FGID: Functional gastrointestinal disorder Table 3. Frequency of abnormal validity and clinical MMPI-2 scales In the different groups of patients (N, (%)). All patients Isolated dyspepsia Isolated IBS Overlap IBS and Dyspepsia Other FGID patients P value Validity scales L scale 87 (13) 19 (14) 9 (13) 29 (14) 30 (11) Infrequency scale (F) 143 (21) 30 (22) 13 (19) 70 (33) 30 (11) <0.001 Infrequency scale back (Fb) 138 (20) 29 (21) 13 (19) 62 (29) 34 (13) <0.001 K scale 18 (3) 3 (2) 1 (1) 6 (3) 8 (3) <0.001 TRIN 78 (11) 13 (9) 9 (13) 28 (13) 28 (10) VRIN 69 (10) 17 (12) 7 (10) 21 (10) 24 (9) Clinical scales 1 Hypochondriasis (Hs) 306 (44) 73 (53) 34 (50) 137 (64) 62 (23) < Depression (D) 181 (26) 43 (31) 17 (25) 80 (37) 41 (15) < Hysteria (Hy) 176 (25) 44 (32) 21 (31) 83 (39) 28 (10) < Psychopathic Deviate (Pd) 71 (10) 15 (11) 9 (13) 28 (13) 19 (7) Masculinity-Femininity (Mf) 58 (8) 8 (6) 7 (10) 19 (9) 24 (9) Paranoia (Pa) 108 (16) 23 (17) 11 (16) 51 (24) 23 (8) < Psychasthenia (Pt) 119 (17) 27 (19) 12 (18) 50 (23) 30 (11) Schizophrenia (Sc) 122 (18) 25 (18) 13 (19) 56 (26) 28 (10) < Hypomania (Ma) 53 (8) 11 (8) 8 (12) 22 (10) 12 (4) Social Introversion (Si) 63 (9) 14 (10) 8 (12) 21 (10) 20 (7) Abbreviations: IBS: irritable bowel syndrome; FGID: Functional gastrointestinal disorder 4. Discussion The present study shows that dyspeptic patients, independently of the association with IBS, have a particular psychological profile characterized by high hypochondriasis scale. Epidemiological evidence suggested that patients with functional dyspepsia have a higher incidence of psychological disorders than population controls [28]. Symptoms of neurosis, anxiety, hypochondriasis, hostility and depression were found to be more common in patients with unexplained gastrointestinal complaints when compared with controls [21, 29, 30]. Many studies have also suggested possible links between emotional factors and alteration in gut physiology such an abnormal gastric secretion, and gut dysmotility [11, 31-33]. Nevertheless, the literature shows insufficient evidence to confirm the efficacy of psychological intervention in the treatment of functional dyspepsia [13]. High hypochondriasis level was also associated with gastric dysmotility in patients with functional dyspepsia [14], with the onset of GERD [34] but not with functional dyspepsia associated with Helicobacter Pylori infection [35]. Several oldest studies emphasized the association of

7 American Journal of Psychology and Behavioral Sciences 2018; 5(1): functional dyspepsia with lower BMI and hypochondriasis in female patients [36-38]. However these studies used different definitions of functional dyspepsia as well as of hypochondriasis. The association of these three characteristics are found in the present study. More recent studies have shown high score of hypochondriasis in other digestive disorders as slow transit constipation [39]. According to Brousset [40], the hypochondriasis or the somatization disorder, as defined in DSM-IV, may be transitory and occurs in 3 major categories: the nosophobia and health/illness anxiety in neurosis or in a depression occurring during a neurosis, in melancholic-type major depression, and hypochondriasis that occurred as early signs of schizophrenia or paranoia. Published in 1943, MMPI is the most widely used and researched standardized psychometric test of adult personality [41]. This test was used to assess psychological profile of many patients with digestive disorders [39, 42, 43], mainly to characterize the organic part and the psychological part of functional gastrointestinal disorders as functional dyspepsia and IBS [11], or slow transit constipation [39]. MMPI-2 was the first major revision of the MMPI. This test was standardized on a national sample of adults in the United States and released in 1989 [27]. In this test, many subscales were introduced to help clinicians in the interpretation of the results of the original clinical scales. In agreement with the weak number of subjects in some groups of patients, we decided to limit this study to the clinical scales of this test; nevertheless, all parameters are indicated in the Annex section. In the MMPI-2, the Hypochondriasis scale (Hs) contains 32 items that focus on bodily concerns. Only 2 of them concern directly epigastric pain. Initially developed on a group of neurotic patients who presented a variety of somatic complaints with no organic basis, this scale has no association with the Harris-Lingoes Scales. A marked elevation of HS scale (T-Scores > 65) is indicative of individuals who have excessive bodily concerns, see themselves as medically ill, seek medical treatments and reject doctor s assurances that there is no physical disorder. These individuals may have conversion disorder or somatic delusions. They describe vague somatic complaints, a filing of chronic weakness and lack of energy and sleep disturbance. They may have a strong psychological component to their illness and are likely to be diagnosed as having somatoform, depressive, or anxiety disorders. However good indication for psychotherapy, they resist psychological explanation of their symptoms, lack insight, become critical of their therapist and terminate therapy prematurely when the therapist suggest psychological issues [44]. In previous studies, psychological illness was often associated with FD: high level of depression and anxiety are worldwide found [16, 17, 20, 45-47], and a 8-weeks treatment with antidepressant improved the quality of life of FD patients [18]; this study showed that the degree of anxiety was an independent factor associated with health care seeking behavior in dyspeptic patients. Depression and somatization levels were recently found associated with increased postprandial symptoms in IBS patients [17]. The present study shows that in patients with functional dyspepsia, overlap with IBS is associated with increase of psychological parameters only in nonspecific dyspepsia patients. This result allows to postulate that psychological morbidities is more pregnant in nonspecific dyspepsia patients and Among all drugs proposed for the treatment of FD [48], recent studies focused on antidepressant and antagonist of the histamine receptor H1. Mirtazapine, an alpha2 noradrenergic and 5-HT2C and 5-HT-3 serotonergic antidepressant was also used as an anxiolytic, hypnotic, antiemetic and appetite stimulant. This drug significantly improved early satiation, quality of life, gastrointestinal-specific anxiety, nutrient tolerance, and weight loss in patients with FD in a randomized, placebo-controlled trial [49]. Among the other serotonergic psychotropic agents proposed for the treatment of functional dyspepsia, buspirone, a 5-HT1A receptor agonist, enhanced gastric relaxation [50]. This anxiolytic drug, primarily used to treat generalized anxiety disorder, 10 mg p.o. twice daily, decreased postprandial aggregate symptom and nausea scores after a fully satiating liquid nutrient meal. In a double-blind, placebo-controlled, randomized trial, the reduction in fullness, bloating, belching, and nausea, as well as overall dyspepsia severity score were associated with increased postprandial accommodation, but there were no significant effects on gastric emptying or sensation thresholds in response to balloon distension in the stomach [51]. In addition, buspirone does not carry the risk of physical dependence and withdrawal symptoms for which those drug classes are known. Enhancement occurred in patients independently of the Helicobacter pylori infection status, with a greater response in female subjects, in both patients and healthy volunteers [52]. Despite buspirone appears efficacious in the improvement of functional dyspepsia, clinical trials of buspirone for the treatment of FD are generally small, and further randomized studies are needed to appreciate the importance of the treatment of hypochondriasis and anxiety in the improvement of symptoms of functional dyspepsia. Among the limitations of the present study, some feature must be underlined: patients are recruited in a tertiary center, and selected by using a complete that could limits the extrapolation to all dyspeptic patients. In our center, a full evaluation (morphological, serological testing for coeliac disease, lactulose breath test, ph-metry, etc..) are performed to exclude organic explanations for their symptoms. In addition, some groups have small size that limits the clinical implications of this study, in particular, the importance of the different IBS subtypes as previously shown [53]. 5. Conclusion This study shows that, in FGIDs patients, high MMPI-II hypochondriasis scale is associated with functional dyspepsia and is increased in patients that have overlap between IBS and functional dyspepsia.

8 8 Michel Bouchoucha et al.: The Importance of Hypochondriasis in Dyspeptic Patients Authorship Statement A. MB did the research, contributed to the design of the study, performed data analysis, participated in the interpretation of data, wrote the article, revised the article for its content, and approved its final version. B. MH performed the research, participated in the interpretation of the data, wrote the article, revised the article for its content, and approved its final version. C. PR participated in the selection of the patients, revised the article content and gave final approval for the version to be published D. GA participated in the selection of the patients, revised the article content and gave final approval for the version to be published E. FM participated in the selection of the patients, revised the article content and gave final approval for the version to be published F. RB contributed to the design of the study, participated in the selection of the patients, revised the article content and gave final approval for the version to be published Competing Interests Michel BOUCHOUCHA, Maria HEJNAR, Florence MARY, Pierre ROMPTEAUX, Gheorghe AIRINEI, and Robert BENAMOUZIG have no competitive interests. Abbreviations BMI FD FGID GI IBS MMPI References Body mass index Functional dyspepsia Functional gastrointestinal disorder Gastrointestinal Irritable bowel syndrome Minnesota Multiphasic Personality Inventory [1] Tack, J., et al., Functional gastroduodenal disorders. Gastroenterology, (5): p [2] Alander, T., et al., Psychological illness is commonly associated with functional gastrointestinal disorders and is important to consider during patient consultation: a population-based study. BMC Med, : p. 8. [3] Longstreth, G. F., et al., Functional bowel disorders. Gastroenterology, (5): p [4] Bouchoucha, M., G. Devroede, and M. Arsac, Anismus: a marker of multi-site functional disorders? Int J Colorectal Dis, (4): p [5] Drossman, D. A., The functional gastrointestinal disorders and the Rome III process. Gastroenterology, (5): p [6] Agreus, L., et al., Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology, (3): p [7] Quigley, E. M., et al., A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome. J Clin Gastroenterol, (5): p [8] Engel, G. L., The need for a new medical model: a challenge for biomedicine. Psychodyn Psychiatry, (3): p [9] Tanaka, Y., et al., Biopsychosocial model of irritable bowel syndrome. J Neurogastroenterol Motil, (2): p [10] Drossman, D. A., et al., Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome. Gastroenterology, (3): p [11] Talley, N. J., et al., Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome. Gastroenterology, (2): p [12] Bennett, E. J., et al., Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut, (2): p [13] Soo, S., et al., Psychological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev, 2005(2): p. CD [14] Kawakami, H., et al., Personality deviation and gastric motility in patients with functional dyspepsia. J Clin Gastroenterol, Suppl 1: p. S [15] Mahadeva, S. and K. L. Goh, Letter: dyspepsia, anxiety and depression. Aliment Pharmacol Ther, (1): p [16] Mak, A. D., et al., Dyspepsia is strongly associated with major depression and generalised anxiety disorder - a community study. Aliment Pharmacol Ther, (8): p [17] Van Oudenhove, L., et al., Depression and Somatization are Associated with Increased Postprandial Symptoms in Patients With Irritable Bowel Syndrome. Gastroenterology, [18] Mahadeva, S. and K. L. Goh, Anxiety, depression and quality of life differences between functional and organic dyspepsia. J Gastroenterol Hepatol, Suppl 3: p [19] Lee, S. P., et al., The effect of emotional stress and depression on the prevalence of digestive diseases. J Neurogastroenterol Motil, (2): p [20] Haug, T. T., et al., Psychological factors and somatic symptoms in functional dyspepsia. A comparison with duodenal ulcer and healthy controls. J Psychosom Res, (4): p [21] Haug, T. T., et al., Life events and stress in patients with functional dyspepsia compared with patients with duodenal ulcer and healthy controls. Scand J Gastroenterol, (6): p [22] Whitehead WE and the Validation Working Team in Association with the Rome Questionnaire Committee, Development and Validation of the Rome III Diagnostic Questionnaire., in Rome III: The functional gastrointestinal disorders., C. E. Drossman DA, Talley NJ, Al e (eds.):, Editor , Degnon Associates: Mc Lean, VA. [23] Galmiche, J. P., et al., Functional esophageal disorders. Gastroenterology, (5): p

9 American Journal of Psychology and Behavioral Sciences 2018; 5(1): [24] Clouse, R. E., et al., Functional abdominal pain syndrome. Gastroenterology, (5): p [25] Bharucha, A. E., et al., Functional anorectal disorders. Gastroenterology, (5): p [26] Graham, J. R., MMPI-2: Assessing Personality and Psychopathology 5th ed. 2011, Oxford: Oxford University Press [27] Butcher, J. N., et al., The Minnesota Multiphasic Personality Inventory-2 (MMPI-2): Manual for administration and scoring. 1989, Minneapolis, MN: University of Minnesota Press. [28] Alpers, D. H., Why should psychotherapy be a useful approach to management of patients with nonulcer dyspepsia? Gastroenterology, (3): p [29] O'Malley, P. G., et al., The value of screening for psychiatric disorders prior to upper endoscopy. J Psychosom Res, (2): p [30] Shukla, G. D., D. N. Mishra, and A. K. Agarwal, Non-organic dyspepsia: a controlled psychometric study. Indian J Psychiatry, (3): p [31] Van Oudenhove, L. and J. Tack, New epidemiologic evidence on functional dyspepsia subgroups and their relationship to psychosocial dysfunction. Gastroenterology, (1): p [32] Hamilton, J., et al., A randomized controlled trial of psychotherapy in patients with chronic functional dyspepsia. Gastroenterology, (3): p [33] Aro, P., et al., Anxiety is associated with uninvestigated and functional dyspepsia (Rome III criteria) in a Swedish population-based study. Gastroenterology, (1): p [34] Barcelo, M., et al., Weight Gain and Somatization are Associated With the Onset of Gastroesophageal Reflux Diseases: Results of Two 5-year Follow-up Studies. J Clin Gastroenterol, [35] Andersson, S. I., et al., Dyspepsia in general practice: psychological findings in relation to Helicobacter pylori serum antibodies. J Psychosom Res, (3): p [36] Marce, L. V., Note sur une forme de délire hypocondriaque consécutive aux dyspepsies et caractérisée principalement par le refus d aliments. Annales médico-psychologiques, (6): p [37] Frank, J.-P., Traité de médecine pratique. Vol , Paris: J-B Baillière. [38] Hare, E., The history of 'nervous disorders' from 1600 to 1840, and a comparison with modern views. Br J Psychiatry, : p [39] Devroede, G., et al., Idiopathic constipation by colonic dysfunction. Relationship with personality and anxiety. Dig Dis Sci, (9): p [40] Brousset, B., L Hypocondrie: Thématique ou Organisation spécifique? Revue Française de psychosomatique, (22): p [41] Hathaway, S. R., A coding system for MMPI profile classification. J Consult Psychol, (6): p [42] Thumshirn, M., et al., Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function. Gut, (1): p [43] Heymen, S., S. D. Wexner, and A. D. Gulledge, MMPI assessment of patients with functional bowel disorders. Dis Colon Rectum, (6): p [44] Butcher, J. N. and C. L. Williams, Essentials of MMPI-2 and MMPI-A Interpretation. Vol , Minneapolis, MN 55401: University of Minnesota Press [45] Strid, H., et al., Impact of sex and psychological factors on the water loading test in functional dyspepsia. Scand J Gastroenterol, (7): p [46] Faramarzi, M., et al., Psychological factors in patients with peptic ulcerand functional dyspepsia. Caspian J Intern Med, (2): p [47] Nan, J., et al., Brain-based Correlations Between Psychological Factors and Functional Dyspepsia. J Neurogastroenterol Motil, (1): p [48] Grover, M. and M. Camilleri, Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases. J Gastroenterol, (2): p [49] Tack, J., et al., Efficacy of Mirtazapine in Patients With Functional Dyspepsia and Weight Loss. Clin Gastroenterol Hepatol, [50] Van Oudenhove, L., et al., Influence of buspirone on gastric sensorimotor function in man. Aliment Pharmacol Ther, (11-12): p [51] Tack, J., et al., Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol, (11): p [52] Dinan, T. G., et al., A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced? Aliment Pharmacol Ther, (10): p [53] Bouchoucha, M., et al., Psychological profiles of irritable bowel syndrome subtypes., in Digestive Diseases Week. 2016, Gastroenterology: San Diego. p. S732.

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