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High Somatic Symptom Burdens and Functional Gastrointestinal Disorders

  • Gregory S. Sayuk
    Correspondence
    Address requests for reprints to: Gregory S. Sayuk, MD, Instructor, Division of Gastroenterology, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8124, St Louis, Missouri 63110. fax: (314) 454-5107.
    Affiliations
    Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri
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  • Jill E. Elwing
    Affiliations
    Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri
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  • Patrick J. Lustman
    Affiliations
    Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri

    Department of Veterans Affairs Medical Center, St Louis, Missouri
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  • Ray E. Clouse
    Affiliations
    Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri

    Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
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Published:January 31, 2007DOI:https://doi.org/10.1016/j.cgh.2006.11.024
      Background & Aims: Unexplained, multi-system somatic symptoms and syndromes, the hallmark features of somatization, are prevalent in patients with functional gastrointestinal disorders (FGIDs). We studied outpatients attending a gastroenterology clinic to see whether current somatic symptom burdens (a somatization state measure) or number of prior functional diagnoses (a somatization trait measure) could predict the presence of an FGID over structural gastrointestinal disease, and whether the predictive value was dependent on comorbid depression or anxiety disorders. Methods: Clinical data from 327 consecutive new referrals to an outpatient gastroenterology practice were reviewed, 187 with an FGID and 140 with a structural illness. Somatization state and trait were measured by using self-reported current symptoms and functional diagnoses recorded in the medical history, respectively. Psychiatric comorbidity (depression or anxiety disorders) was extracted from chart review. Results: FGID subjects endorsed more somatization state symptoms, had more somatization trait diagnoses, and had greater likelihood of psychiatric comorbidity (P < .001 for each). Logistic regression analysis adjusting for age and sex differences showed that each of these features independently predicted the likelihood of an FGID over structural disease (P < .05 for each). When high ratings on the somatization measures were present together with psychiatric comorbidity, the positive predictive value exceeded 0.95. Conclusions: Higher burdens of either current somatic symptoms or functional diagnoses in the medical history are strong predictors of an FGID in outpatients presenting with gastrointestinal complaints. The mechanism is not solely dependent on a relationship with affective disorders, which independently predicts FGID, at least in part, through another path.

      Abbreviations used in this paper:

      CI (confidence interval), FGID (functional gastrointestinal disorder), IBS (irritable bowel syndrome), OR (odds ratio)
      See Vandenberghe J et al on page 1684 for companion article in the May 2007 issue of Gastroenterology.
      Interest is growing in symptoms from nongastrointestinal sites that are present in patients with functional gastrointestinal disorders (FGIDs). Somatic symptoms and syndromes across several organ systems and unexplained by physical illness are reported by at least one fourth of patients,
      • North C.S.
      • Downs D.
      • Clouse R.E.
      • et al.
      The presentation of irritable bowel syndrome in the context of somatization disorder.
      a phenomenon called somatization.
      • Clouse R.E.
      • Lustman P.J.
      Use of psychopharmacological agents for functional gastrointestinal disorders.
      The biologic underpinnings of somatization remain unknown; its presence and degree are determined crudely by the clinical expression of medically unexplained symptoms. Because the FGIDs also lack a defined physical basis, it is possible that they represent a component of the somatization process, or at least that the neurophysiologic mechanisms underlying somatization have a relevant role in the development or presentation of FGIDs.
      • Clouse R.E.
      • Lustman P.J.
      Use of psychopharmacological agents for functional gastrointestinal disorders.
      For research purposes, somatization has been operationalized in several fashions.
      • Kirmayer L.J.
      • Robbins J.M.
      Three forms of somatization in primary care: prevalence, co-occurrence, and sociodemographic characteristics.
      • Simon G.E.
      • Von Korff M.
      Somatization and psychiatric disorder in the NIMH Epidemiologic Catchment Area study.
      • Lipowski Z.J.
      Somatization: the experience and communication of psychological distress as somatic symptoms.
      • Kellner R.
      Somatization: theories and research.
      • Katon W.
      • Lin E.
      • Von Korff M.
      • et al.
      Somatization: a spectrum of severity.
      Measures can reflect the somatization state, an expression of recent medically unexplained symptoms, or the somatization trait, a background of remote functional syndromes provided by the medical history. Some evidence exists that over-reporting of current symptoms provides a method of predicting FGID over structural gastrointestinal disease, supporting the importance of the somatization state.
      • Brown W.H.
      • Chey W.D.
      • Elta G.H.
      Number of responses on a review of systems questionnaire predicts the diagnosis of functional gastrointestinal disorders.
      • Wise J.L.
      • Locke G.R.
      • Zinsmeister A.R.
      • et al.
      Risk factors for non-cardiac chest pain in the community.
      There also is evidence that an increased burden of functional syndromes in the medical history helps define the FGID patient.
      • Whitehead W.E.
      • Palsson O.
      • Jones K.R.
      Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?.
      • Locke 3rd, G.R.
      • Zinsmeister A.R.
      • Fett S.L.
      • et al.
      Overlap of gastrointestinal symptom complexes in a US community.
      Thus, somatization state and trait features both might be pertinent to FGID pathophysiology. Whether these characteristics are fully interrelated or whether each bears independent relevance has not been explored. Addressing such concerns would help determine the relative importance of short-term and long-term processes on FGID expression.
      Depression and anxiety disorders also are comorbid conditions in patients with FGID, diagnosed at presentation or in the past in as much as 60%–70% of patients with irritable bowel syndrome (IBS), for example.
      • North C.S.
      • Downs D.
      • Clouse R.E.
      • et al.
      The presentation of irritable bowel syndrome in the context of somatization disorder.
      • Schwarz S.P.
      • Blanchard E.B.
      • Berreman C.F.
      • et al.
      Psychological aspects of irritable bowel syndrome: comparisons with inflammatory bowel disease and nonpatient controls.
      • Clouse R.E.
      • Alpers D.H.
      The relationship of psychiatric disorder to gastrointestinal illness.
      • Miller A.R.
      • North C.S.
      • Clouse R.E.
      • et al.
      The association of irritable bowel syndrome and somatization disorder.
      • Walker E.A.
      • Roy-Byrne P.P.
      • Katon W.J.
      • et al.
      Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease.
      • Masand P.S.
      • Kaplan D.S.
      • Gupta S.
      • et al.
      Major depression and irritable bowel syndrome: is there a relationship?.
      • Blanchard E.B.
      • Scharff L.
      • Schwarz S.P.
      • et al.
      The role of anxiety and depression in the irritable bowel syndrome.
      The significance of the association remains uncertain; the strongest observation against a direct relationship is the dissociated response of FGID symptoms from change in psychometric scale scores with successful treatment of the gastrointestinal symptoms.
      • Jackson J.L.
      • O’Malley P.G.
      • Tomkins G.
      • et al.
      Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis.
      • Drossman D.A.
      • Toner B.B.
      • Whitehead W.E.
      • et al.
      Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders.
      • Clouse R.E.
      • Lustman P.J.
      • Eckert T.C.
      • et al.
      Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities: a double-blind, placebo-controlled trial.
      Somatization might serve as a mediator of the relationship between FGID and psychiatric comordibity, considering the commingling of anxiety and depression with advanced degrees of somatization observed in small samples of IBS patients.
      • Miller A.R.
      • North C.S.
      • Clouse R.E.
      • et al.
      The association of irritable bowel syndrome and somatization disorder.
      Whether somatization state features or trait features have greater bearing on this relationship is yet to be examined.
      We hypothesized that high somatic symptom counts and histories of abundant prior functional diagnoses would each independently predict the diagnosis of an FGID over a structural gastrointestinal disease in an outpatient population after controlling for potentially confounding factors, supporting the importance of both recent and chronic somatization toward susceptibility to FGIDs. We also hypothesized that comorbid psychiatric illness (depression or anxiety disorder) would not have independent predictive value toward an FGID diagnosis once the contributions from the somatization measures were taken into account. Thus, the previously observed relationship of psychiatric illness with FGID primarily would relate to its relationship with somatization. A retrospective review of chart data from a university-based practice was used to test these hypotheses.

      Methods

      Subjects

      Consecutive patients identified from billing records, seen in an outpatient university-based adult gastroenterology practice either initially or in follow-up during a 2-year period from January 1, 2003–January 1, 2005 and followed for at least 3 months, provided the primary subject pool. Subjects were stratified into 3 groups on the basis of chart notations made by the treating physician: (1) an FGID group, in which a functional disorder had been considered responsible for the presenting symptoms; (2) a structural gastrointestinal disease group, in which a structural illness had been established and had been considered sufficient to explain the presenting symptoms; and (3) a group in which a structural illness had been identified but was considered insufficient to explain symptoms, according to the chart notations. The last group was excluded from the primary analyses. FGIDs are diagnosed in this outpatient office according to a criteria-based system (Rome II),
      • Drossman D.
      • Thompson W.
      • Whitehead W.
      • et al.
      and the 3-month follow-up requirement was imposed to ensure stability of the functional or structural diagnosis. Review of clinical records for the purposes of this study was approved by the Washington University Human Studies Committee before study conception.

      Record Review

      Clinical features, including demographic characteristics and the diagnosis to which symptoms were attributed, were systematically extracted from the outpatient record by using an instrument prepared a priori for data extraction. All clinical notations, including records from office visits, telephone contacts, or written communications, were considered potential sources of clinical data. Although the investigators performing the record reviews were not blinded to subject diagnosis, they were unaware of the study hypotheses being tested.
      Two measures of somatization were extracted. Each subject had completed a self-reported review-of-systems checklist at the initial visit. This checklist is composed of 60 symptoms across 10 organ systems, and subjects had been asked to endorse only those symptoms that were “currently” experienced. Total numbers of endorsed symptoms and systems were recorded, as were responses to a subset of 13 symptoms that represented 13 of 15 symptoms included in a previously validated measure of somatic symptom severity (Table 1).
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.
      The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms.
      A high degree of somatization state was considered present for descriptive purposes in characterizing subject group if endorsement was at or above the median (≥6 symptoms). A second measure assessed somatization trait as the sum of all documented patient-reported or physician-determined gastrointestinal and nongastrointestinal functional disorders (symptoms or syndromes that were unexplained medically) that had been recorded in the history (eg, fibromyalgia, chronic headache). For descriptive purposes, a high degree of somatization trait was considered present if, in addition to the primary FGID, ≥2 functional disorders had been established in that individual. This threshold corresponded to the median value in a previously reported group of FGID patients who had been deemed candidates for antidepressant therapy.
      • Sayuk G.S.
      • Elwing J.E.
      • Lustman P.J.
      • et al.
      Predictors of premature antidepressant discontinuation in functional gastrointestinal disorders (FGIDs): a survival analysis approach.
      Table 1Symptoms Included in the Somatization State Measure
      Excludes sexual symptoms included in the PHQ-15.
      General
       Lack of energy/fatigue
      Cardiovascular
       Chest pain
       Heart palpitations
       Shortness of breath
      Musculoskeletal
       Back pain
       Joint pain/muscle ache
      Gastrointestinal
       Belching/bloating/nausea
       Changes in stool form
       Stomach pain
      Neurologic
       Dizziness
       Fainting
       Headache
      Psychiatric
       Difficulty sleeping
      Modified from Kroenke et al.
      • Kroenke K.
      Physical symptom disorder: a simpler diagnostic category for somatization-spectrum conditions.
      a Excludes sexual symptoms included in the PHQ-15.
      Psychiatric comorbidity was considered present when a diagnosis of depression or an anxiety disorder was available in the medical record, having been made in the past or coexistent with the gastrointestinal disorder. Psychiatric diagnoses are made in this outpatient office by using criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Version IV,
      but a specific interview or instrument is not used. Patient-reported diagnoses of depression or an anxiety disorder also were accepted as evidence of psychiatric illness. Only depression and anxiety disorders were included because together these constitute the most common psychiatric diagnoses encountered in patients with FGID.
      • Whitehead W.E.
      • Palsson O.
      • Jones K.R.
      Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?.
      • Lydiard R.B.
      • Fossey M.D.
      • Marsh W.
      • et al.
      Prevalence of psychiatric disorders in patients with irritable bowel syndrome.

      Statistical Methods

      Measures of central tendency are reported as mean ± standard error of the mean for continuous variables and median values with ranges for categorical data. Group data were compared by using Student t tests for continuous data and χ2 tests for binomial data. The overlapping of somatization state, somatization trait, and psychiatric illness was explored through the calculation of Pearson correlation coefficients and the generation of Venn diagrams. Positive predictive values were calculated as the proportion of true positives over the sum of true positives plus false positives. Logistic regression modeling without elimination was used to evaluate predictors of FGID over structural gastrointestinal disease. The somatization measures were used as continuous variables in the models. Statistical analyses were conducted by using SPSS v14.0 (SPSS Inc, Chicago, IL), with a P value <.05 as a determinant of statistical significance in two-tailed testing.

      Results

      Demographic and Disorder Characteristics

      A total of 524 potential subjects were identified during the 2-year study period, 127 of whom had either incomplete or unretrievable records (n = 32) or had not been followed for 3 months (n = 95). Of the remaining 397 subjects, 70 fell into the third subject group, had presenting symptoms that were not fully explained by the identified structural gastrointestinal disease, and were not considered in the primary analyses. The 327 other subjects had a mean of 44.9 ± 0.9 months of clinical follow-up available for chart review. A summary of baseline demographic characteristics is provided in Table 2.
      Table 2Demographic Characteristics of the Subjects
      CharacteristicAll subjects (n = 327)Subjects with FGID (n = 187)Subjects with a structural gastrointestinal disease (n = 140)P value
      Comparing subjects with FGID with those with structural gastrointestinal disease.
      Age, mean ± SEM (y)46.1 ± 0.845.6 ± 1.245.3 ± 1.6.9
      Sex, n (%)
       Female198 (60.6)131 (70.1)67 (47.9)<.001
       Male129 (39.4)56 (29.9)73 (52.1)
      Race, n (%)
       Non-white6 (1.8)4 (2.1)2 (1.4).7
       White321 (98.2)183 (97.9)138 (98.6)
      a Comparing subjects with FGID with those with structural gastrointestinal disease.
      FGID had been diagnosed in 187 subjects (57.2%), the most common of which was IBS (n = 49, 26.2% of the FGID subjects). Functional esophageal disorders had been identified in 25 (13.3%; chest pain, n = 9; dysphagia, n = 10, other functional esophageal disorders, n = 6), functional gastroduodenal disorders in 60 (32.0%; functional dyspepsia, n = 19; functional vomiting disorders, n = 39; other functional gastroduodenal disorders, n = 2), and non-IBS functional bowel disorders in an additional 53 (28.3%; functional abdominal pain, n = 23; functional constipation, n = 10; functional diarrhea, n = 7; functional bloating, n = 4; other functional bowel disorders, n = 9). The FGID group had a significantly higher proportion of female subjects than the group with structural gastrointestinal disease (Table 2).
      Symptoms had been attributed to a structural gastrointestinal disease in 140 subjects (42.8%). Gastroesophageal reflux disease was the most common diagnosis in this group, being identified in 42 subjects (30.0% of all structural diagnoses). Additional prevalent diagnoses included ulcerative colitis (n = 35, 25.0%), achalasia (n = 20, 14.3%), and Crohn’s disease (n = 14, 10.0%). Twenty-nine subjects (20.7%) had a variety of other gastrointestinal diseases.

      Somatization Measures and Psychiatric Comorbidity

      Subjects with FGID were significantly more likely than their structural disease counterparts to have a high degree of somatization state, a high degree of somatization trait, and psychiatric comorbidity (Figure 1). With regard to current somatic symptoms at the time of presentation, subjects with FGID had endorsed more symptoms over more systems on the review-of-systems checklist and almost twice as many specific somatic symptoms on the somatization state measure than subjects with structural gastrointestinal disease (Table 3). More functional disorders, other than the primary diagnosis, used in the somatization trait measure also were found in the histories of patients with FGID (Table 3). The most common of these additional disorders are listed in Table 3. Greater proportions of subjects in the FGID group had been given diagnoses of both depression and anxiety disorders than subjects with structural gastrointestinal disease (23.5% vs 6.4% and 20.3% vs 7.1%, respectively; P ≤ .001 for each comparison).
      Figure thumbnail gr1
      Figure 1Percentage of subjects with high ratings on the somatization scales and with comorbid psychiatric illness (depression or an anxiety disorder) by subject group. Each feature was more common in subjects with FGID. *P < .001 compared with subjects with structural gastrointestinal disease.
      Table 3Summary of Somatization Features
      MeasureAll subjects (n = 327)Subjects with FGID (n = 187)Subjects with structural gastrointestinal disease (n = 140)P value
      Comparing subjects with FGID with those with structural gastrointestinal disease.
      Review-of-systems checklist
       No. of systems endorsed,
      Out of a total of 10 possible systems.
      mean ± SEM
      3.9 ± 0.24.6 ± 0.23.1 ± 0.2<.001
       No. of current symptoms,
      Out of a total of 60 possible symptoms.
      mean ± SEM
      9.2 ± 0.411.2 ± 0.66.5 ± 0.5<.001
       Somatization state measure symptoms,
      Out of a total of 13 possible symptoms.
      mean ± SEM
      3.4 ± 0.14.3 ± 0.22.3 ± 0.2<.001
      Medical history review
       Prevalence of nongastrointestinal functional disorders,
      In descending order; those with <10 total subjects not listed.
      n (%)
        Chronic headache61 (18.7)48 (25.7)13 (9.3)<.001
        Back pain36 (11.0)24 (12.8)12 (8.6).15
        Somatosensory disturbance36 (11.0)31 (16.6)5 (3.6)<.001
        Chronic pelvic pain11 (3.4)10 (5.3)1 (0.7).02
        Fibromyalgia8 (2.4)7 (3.7)1 (0.7).08
       No. of somatization trait disorders, mean ± SEM1.7 ± 0.12.6 ± 0.10.5 ± 0.1<.001
      a Comparing subjects with FGID with those with structural gastrointestinal disease.
      b Out of a total of 10 possible systems.
      c Out of a total of 60 possible symptoms.
      d Out of a total of 13 possible symptoms.
      e In descending order; those with <10 total subjects not listed.
      The relationships between somatization state, somatization trait, and psychiatric comorbidity for each subject group are shown in Figure 2. In both groups the somatization state and trait measures were modestly but significantly correlated (r = 0.44 and r = 0.41, respectively; P < .001 for each). Within the FGID group, the presence of a psychiatric diagnosis portended a higher scale score on the somatization state measure (5.2 ± 0.3 vs 2.8 ± 0.1, P = .01) and was associated with a greater number of functional disorders on the somatization trait measure (3.5 ± 0.2 vs 1.1 ± 0.1, P < .001). There were no differences in somatization scale scores by psychiatric comorbidity status in the group with structural gastrointestinal disease. The greater degree of commingling of all 3 features within the FGID group is apparent from review of Figure 2.
      Figure thumbnail gr2
      Figure 2Proportion-appropriate Venn diagrams showing the degree of overlap between somatization features and psychiatric comorbidity by subject group. A high degree of somatization state (SOM-S) overlapped with a high degree of somatization trait (SOM-T) in each group, but their degree of overlap and the amount of commingling with psychiatric comorbidity (PSYCH) were greater in the group with FGID. The numbers in the diagrams represent the percentages of subjects falling into each segment.

      Predictors of Functional Gastrointestinal Disorders

      Results from logistic regression modeling of clinical and demographic predictors of FGID are summarized in Table 4. Female sex, psychiatric comorbidity, and greater scores on the somatization measures each independently predicted the presence of an FGID over a structural gastrointestinal disease. When the same analysis was conducted including within the FGID group the 70 initially excluded subjects who had symptoms out of proportion to a structural gastrointestinal disease (ie, suspected functional symptoms concurrent with the structural disease), the identical predictors were identified (female sex: odds ratio [OR], 2.43; 95% confidence interval [CI], 1.51–3.90; psychiatric comorbidity: OR, 2.34; 95% CI, 1.24–4.42; somatization state symptoms: OR, 1.30; 95% CI, 1.15–1.48; somatization trait disorders: OR, 1.37; 95% CI, 1.02–1.83).
      Table 4Predictors of the Presence of FGID in This Outpatient Practice
      PredictorOR95% CIP value
      Age1.000.98–1.01.8
      Female sex2.451.47–4.08.001
      Psychiatric comorbidity
      Presence of a diagnosis of depression or an anxiety disorder.
      2.471.27–4.80.01
      Somatization state symptoms
      Measure used as a continuous variable.
      1.271.11–1.46.001
      Somatization trait disorders
      Measure used as a continuous variable.
      1.411.05–1.91.02
      a Presence of a diagnosis of depression or an anxiety disorder.
      b Measure used as a continuous variable.
      The cumulative contribution of psychiatric comorbidity and high degrees of somatization state and trait on the predictive value of an FGID was examined for each sex and for the whole subject group (Figure 3). With an increasing number of features, the likelihood of diagnosing an FGID increased linearly. Whereas subjects without psychiatric comorbidity and with low degrees of somatization had less than 50% likelihood of having an FGID, nearly 90% of subjects with any 2 features had an FGID, and more than 95% of subjects with all 3 features ultimately were diagnosed as having an FGID to explain the presenting symptoms.
      Figure thumbnail gr3
      Figure 3Positive predictive value for being diagnosed with an FGID over structural gastrointestinal disease in this study population by cumulative number of somatization and psychiatric features (high somatization state, high somatization trait, psychiatric comorbidity). Subjects without any features were equally likely to have a functional or structural disorder. Presence of all 3 features had a positive predictive value of 96% for FGID.

      Discussion

      In this study we found an increase in the number of current somatic symptoms and previous functional disorders in outpatients with FGID at a university-based practice when compared with those having structural gastrointestinal diseases. As expected, psychiatric comorbidity (depression and anxiety disorders) also was more prevalent in the former subject group. In support of our hypotheses, each somatization measure independently predicted the presence of an FGID. The relationship of psychiatric comorbidity to FGID, however, was not completely mediated by somatization, because psychiatric comorbidity was retained as an independent predictor in the regression analysis. The same outcomes were found when subjects with symptoms out of proportion to structural disease were included. Thus, high current somatic symptom burdens, abundant past functional disorders, and psychiatric comorbidity each helped identify patients with functional gastrointestinal symptoms, whether structural gastrointestinal disease was present or not. The predictive value was pronounced in this outpatient population; the patient with high ratings on both somatization scales as well as a history of depression or an anxiety disorder had >95% likelihood of having an FGID.
      Nongastrointestinal somatic symptoms and syndromes, usually also functional in origin, have long been observed in patients with FGID.
      • Whitehead W.E.
      • Palsson O.
      • Jones K.R.
      Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?.
      For example, fibromyalgia is diagnosed in as many as two thirds of patients with IBS.
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      Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?.
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      Similar data exist for chronic fatigue syndrome, temporomandibular joint disorder,
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      Somatic comorbidities have been considered almost at the level of curiosities and usually are examined individually, depending on the interests of the medical subspecialty conducting the research. Recently, a high collective somatic symptom burden in IBS patients
      • Walker E.A.
      • Roy-Byrne P.P.
      • Katon W.J.
      • et al.
      Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease.
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      Prevalence of psychiatric disorders in patients with irritable bowel syndrome.
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      has been found to result in greater reported bowel symptom severity,
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      Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia.
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      impact negatively on physical functioning and quality of life,
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      Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications.
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      • Harris W.
      • Ricci J.–F.
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      interfere with treatment adherence,
      • Sayuk G.S.
      • Elwing J.E.
      • Lustman P.J.
      • et al.
      Predictors of premature antidepressant discontinuation in functional gastrointestinal disorders (FGIDs): a survival analysis approach.
      and lead to increased usage of heath care resources.
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      • Kanwal F.
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      • et al.
      The impact of somatization on the use of gastrointestinal health-care resources in patients with irritable bowel syndrome.
      Thus, the importance of somatic comorbidities with regard to outcomes in FGID is becoming established. Their impact on the pathophysiology of these disorders and contribution toward risk of developing FGID are less appreciated or understood.
      Current nomenclature defines the presence of multiple medically unexplained symptoms as somatization, a poorly understood process that has been relegated to the field of psychiatry.
      Several lines of investigation indicate that somatization is relevant to the development or expression of FGIDs, disorders that might actually be components of the process. First, the few available cross-sectional studies demonstrate high rates of somatization in FGID patient groups. At least 25% of IBS subjects attending a university-based outpatient practice qualify for the diagnosis of somatization disorder, a particularly severe form of somatization that is rare in non-patient samples.
      • North C.S.
      • Downs D.
      • Clouse R.E.
      • et al.
      The presentation of irritable bowel syndrome in the context of somatization disorder.
      • Miller A.R.
      • North C.S.
      • Clouse R.E.
      • et al.
      The association of irritable bowel syndrome and somatization disorder.
      Linkage of somatization with FGID also was found in a community-based sample of non-patients,
      • Locke 3rd, G.R.
      • Weaver A.L.
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      • et al.
      Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study.
      and somatization has been associated with the level of symptom reporting.
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      • Maganti K.
      Symptoms, gastric function, and psychosocial factors in functional dyspepsia.
      Similarly, somatization predicts the symptom response to gastrointestinal stimuli in some tested FGIDs.
      • Gwee K.A.
      • Leong Y.L.
      • Graham C.
      • et al.
      The role of psychological and biological factors in postinfective gut dysfunction.
      • Whitehead W.E.
      • Palsson O.S.
      Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception.
      Second, somatization at baseline is an independent predictor of postinfectious IBS when subjects are followed longitudinally.
      • Gwee K.A.
      • Leong Y.L.
      • Graham C.
      • et al.
      The role of psychological and biological factors in postinfective gut dysfunction.
      • Whitehead W.E.
      • Palsson O.S.
      Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception.
      Finally, improvement in somatization scale scores has paralleled clinical response when antidepressants were used to treat functional esophageal symptoms in one study,
      • Clouse R.E.
      • Lustman P.J.
      • Eckert T.C.
      • et al.
      Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities: a double-blind, placebo-controlled trial.
      whereas improvements in depression or anxiety symptoms with antidepressants are not related closely to improvement in FGID symptoms.
      • Jackson J.L.
      • O’Malley P.G.
      • Tomkins G.
      • et al.
      Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis.
      • Rajagopalan M.
      • Kurian G.
      • John J.
      Symptom relief with amitriptyline in the irritable bowel syndrome.
      • Lydiard R.B.
      Irritable bowel syndrome, anxiety, and depression: what are the links?.
      Consequently, somatization appears to be the central element linking somatic comorbidity to FGID and possibly represents the diverse expression of a common neurophysiologic process responsible for all the symptoms. The high predictive values of somatization in detecting patients with FGID within our outpatient practice would add support to this hypothesis, at least in one clinical setting.
      In a clinical context, somatization can be measured as somatization state (current symptom reporting) or trait (previous functional disorders); each method depends on the expression of medically unexplained somatic symptoms and not measuring a mechanism per se. Psychiatric criteria largely are restricted to somatization disorder, a pronounced degree of somatization, and take into account both state and trait features in defining the disorder.
      A dialogue is ongoing within the psychiatric literature as to which features are superior in the definition and recognition of somatization.
      • Sharpe M.
      • Mayou R.
      • Walker J.
      Bodily symptoms: new approaches to classification.
      • Mayou R.
      • Kirmayer L.J.
      • Simon G.
      • et al.
      Somatoform disorders: time for a new approach in DSM-V.
      • Kroenke K.
      Physical symptom disorder: a simpler diagnostic category for somatization-spectrum conditions.
      The present study demonstrates the overlapping yet independent importance of somatization state and trait features in predicting the presence of FGID, a novel observation. This finding is important, because somatization state is relatively easily measured with simple self-report instruments, whereas somatization trait typically relies on more extensive medical history taking by trained professionals and systematic record reviews. If somatization features become increasingly important in the assessment, management, or study of patients with FGID, then both types of measures might need incorporation for comprehensive evaluation.
      Psychiatric illness, specifically anxiety and depression, is found on average in 7 in 10 FGID patients.
      • Clouse R.E.
      • Alpers D.H.
      The relationship of psychiatric disorder to gastrointestinal illness.
      • Walker E.A.
      • Roy-Byrne P.P.
      • Katon W.J.
      • et al.
      Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease.
      • Lydiard R.B.
      • Fossey M.D.
      • Marsh W.
      • et al.
      Prevalence of psychiatric disorders in patients with irritable bowel syndrome.
      • Walker E.A.
      • Gelfand A.N.
      • Gelfand M.D.
      • et al.
      Psychiatric diagnoses, sexual and physical victimization, and disability in patients with irritable bowel syndrome or inflammatory bowel disease.
      In spite of repeated observation of comorbidity, the importance of the relationship remains unclear. Miller et al
      • North C.S.
      • Downs D.
      • Clouse R.E.
      • et al.
      The presentation of irritable bowel syndrome in the context of somatization disorder.
      and North et al
      • Miller A.R.
      • North C.S.
      • Clouse R.E.
      • et al.
      The association of irritable bowel syndrome and somatization disorder.
      found that anxiety and depressive symptoms and disorders aggregate with somatization disorder in IBS patients, raising 2 possible explanations for the association. First, the psychiatric illnesses might increase the reporting of somatic symptoms, which, in turn, are but a manifestation of the processes linking depression and anxiety to the FGID. Somatization is a potential manifestation of depression in psychiatric samples, making this theory plausible.
      • Simon G.E.
      • Von Korff M.
      • Piccinelli M.
      • et al.
      An international study of the relation between somatic symptoms and depression.
      Alternatively, the mechanisms behind somatization might increase reporting of psychiatric symptoms (“psychoform” symptoms), as well as somatic symptoms. This phenomenon has been reported previously in psychiatric patients with somatization disorder.
      • Miller A.R.
      • North C.S.
      • Clouse R.E.
      • et al.
      The association of irritable bowel syndrome and somatization disorder.
      • Lenze E.J.
      • Miller A.R.
      • Munir Z.B.
      • et al.
      Psychiatric symptoms endorsed by somatization disorder patients in a psychiatric clinic.
      If the above were operational in our FGID patients, either somatization or psychiatric illness should have fallen out of our multivariate models. Such was not the case, and our hypothesis that psychiatric illness was dependent on somatization in predicting FGID was not supported. Multiple paths linked to somatization and psychiatric illness result in FGID development and/or presentation, or these features mark the presence of an alternative, singular mechanism. Neuroendocrine-immune dysregulation
      • Tache Y.
      • Martinez V.
      • Wang L.
      • et al.
      CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome.
      • Tache Y.
      • Martinez V.
      • Million M.
      • et al.
      Role of corticotropin releasing factor receptor subtype 1 in stress-related functional colonic alterations: implications in irritable bowel syndrome.
      • Tache Y.
      • Martinez V.
      • Million M.
      • et al.
      Corticotropin-releasing factor and the brain-gut motor response to stress.
      • Tache Y.
      Cyclic vomiting syndrome: the corticotropin-releasing-factor hypothesis.
      • Posserud I.
      • Agerforz P.
      • Ekman R.
      • et al.
      Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress.
      • Rief W.
      • Shaw R.
      • Fichter M.M.
      Elevated levels of psychophysiological arousal and cortisol in patients with somatization syndrome.
      and alterations in ascending and inhibitory pain pathways at the central nervous system level
      • Tillisch K.
      • Mayer E.A.
      Pain perception in irritable bowel syndrome.
      • Mayer E.A.
      • Naliboff B.D.
      • Chang L.
      Evolving pathophysiological model of functional gastrointestinal disorders: implications for treatment.
      • Mayer E.A.
      • Berman S.
      • Suyenobu B.
      • et al.
      Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis.
      would be examples of such mechanisms.
      Physiologic measures that provide diagnostic insight into the FGIDs are limited. Clinical predictors thus remain the most useful means of identifying the disorders. In our study, 3 key clinical features (high degree of somatization state, high degree of somatization trait, and psychiatric comorbidity) collectively yielded a striking ability to predict the presence of an FGID. Moreover, these same factors could predict functional symptoms in the face of structural gastrointestinal disease. The predictive values of these features rival existing symptom-based criteria for FGID diagnoses
      • Drossman D.
      • Thompson W.
      • Whitehead W.
      • et al.
      • Lea R.
      • Hopkins V.
      • Hastleton J.
      • et al.
      Diagnostic criteria for irritable bowel syndrome: utility and applicability in clinical practice.
      and possibly should play at least a complementary diagnostic role. As a minimum, their absence would take on the role of a “red flag” disfavoring the diagnosis of an FGID, particularly in male subjects. Illustrating this point, male subjects lacking either a psychiatric diagnosis or high degrees of somatization in our study had less than 30% likelihood of having a functional explanation for presenting symptoms. The predictive values undoubtedly would differ depending on the type of sample (community, primary care, referral practice, etc), and this deserves further investigation.
      This study has significant limitations, primarily related to the nonvalidated measures used for data collection from chart review. The diagnoses required for psychiatric comorbidity were accepted from the medical record and were not determined systematically. Similarly, the somatization trait measure used diagnoses that were present in the record and possibly had not been recorded uniformly across subject groups. A bias favoring a link between FGID and somatization trait diagnoses or psychiatric comorbidity could have been introduced by the clinician if psychiatric and functional diagnoses had been solicited and recorded more intently in patients for whom such features would support the clinical diagnosis. Nevertheless, the strength of the associations is remarkable and begs verification in prospective trials with validated methods. The somatization state measure was based on a well-established instrument (the PHQ-15),
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.
      The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms.
      but it did not use the severity measure of the PHQ-15 and was extracted from a longer-item checklist. It is unlikely that this impaired the performance of the measure, because symptom counts alone are considered valid,
      • Kroenke K.
      • Rosmalen J.G.
      Symptoms, syndromes, and the value of psychiatric diagnostics in patients who have functional somatic disorders.
      • Rief W.
      • Hiller W.
      A new approach to the assessment of the treatment effects of somatoform disorders.
      • Kroenke K.
      • Spitzer R.L.
      • deGruy 3rd, F.V.
      • et al.
      A symptom checklist to screen for somatoform disorders in primary care.
      longer lists of somatic symptoms form the parent instruments of many contemporary somatization scales,
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.
      The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms.
      • Rief W.
      • Hiller W.
      A new approach to the assessment of the treatment effects of somatoform disorders.
      • Kroenke K.
      • Spitzer R.L.
      • deGruy 3rd, F.V.
      • et al.
      A symptom checklist to screen for somatoform disorders in primary care.
      • Swartz M.
      • Hughes D.
      • George L.
      • et al.
      Developing a screening index for community studies of somatization disorder.
      • Othmer E.
      • DeSouza C.
      A screening test for somatization disorder (hysteria).
      • Escobar J.I.
      • Rubio-Stipec M.
      • Canino G.
      • et al.
      Somatic symptom index (SSI): a new and abridged somatization construct—prevalence and epidemiological correlates in two large community samples.
      • Perley M.J.
      • Guze S.B.
      Hysteria: the stability and usefulness of clinical criteria—a quantitative study based on a follow-up period of six to eight years in 39 patients.
      and these inclusive lists are more robust determinants of somatoform disorders than abbreviated measures.
      • Spitzer R.L.
      • Kroenke K.
      • Williams J.B.
      Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study—Primary Care Evaluation of Mental Disorders—Patient Health Questionnaire.
      American Psychiatric Association
      World Health Organization
      An additional limitation of the findings is the lack of generalization because a university-based referral practice served as the source of subjects; findings could be considerably different in community-based gastroenterology settings or in primary care.
      Despite the limitations inherent in the study methodology, our findings highlight the potential importance of somatic symptom and syndrome burden as well as psychiatric comorbidity in identifying patients with FGID. These features potentially reflect a single or several underlying neurophysiologic mechanisms influencing the development or presentation of the gastrointestinal disorders. The findings also have relevance to the measurement of somatization and psychiatric illness in clinical and research applications.

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