Clinical studies have shown that Medically Unexplained Symptoms (MUS) are related to common mental disorders. It is unknown how often common mental disorders occur in subjects who have explained physical symptoms (PHY), MUS or both, in the general population, what the incidence rates are, and whether there is a difference between PHY and MUS in this respect.
To study the prevalence and incidence rates of mood, anxiety and substance use disorders in groups with PHY, MUS and combined MUS and PHY compared to a no-symptoms reference group in the general population.
Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face-to-face survey of the general population aged 18-64 years. We selected subjects with explained physical symptoms only (n=1952), with MUS only (n=177), with both MUS and PHY (n=209), and a reference group with no physical symptoms (n=4168). The assessment of common mental disorders was through the Composite International Diagnostic Interview 3.0. Multivariate logistic regression analyses were used to examine the association between group membership and the prevalence and first-incidence rates of comorbid mental disorders, adjusted for socio-demographic characteristics.
MUS were associated with the highest prevalence rates of mood and anxiety disorders, and combined MUS and PHY with the highest prevalence rates of substance disorder. Combined MUS and PHY were associated with a higher incidence rate of mood disorder only (OR 2.9 (95%CI:1.27,6.74)).
In the general population, PHY, MUS and the combination of both are related to mood and anxiety disorder, but odds are highest for combined MUS and PHY in relation to substance use disorder. Combined MUS and PHY are related to a greater incidence of mood disorder. These findings warrant further research into possibilities to improve recognition and early intervention in subjects with combined MUS and PHY.
Citation: van Eck van der Sluijs J, ten Have M, Rijnders C, van Marwijk H, de Graaf R, van der Feltz-Cornelis C (2015) Medically Unexplained and Explained Physical Symptoms in the General Population: Association with Prevalent and Incident Mental Disorders. PLoS ONE 10(4): e0123274. https://doi.org/10.1371/journal.pone.0123274
Received: September 24, 2014; Accepted: February 18, 2015; Published: April 8, 2015
Copyright: © 2015 van Eck van der Sluijs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Data Availability: The data are from the 'Netherlands Mental Health Survey and Incidence Study-2' (NEMESIS-2) which are owned by a third party, the Netherlands Institute of Mental Health and Addiction (Trimbos Institute), that does not publicly share data. However, all interested parties will be able to obtain data upon request as follows. Researchers can submit a research plan, which describes the background and methods of a proposed research question, and a request for specific data of the NEMESIS-2 database to answer the research question. After approval of the research plan by the principal investigator of NEMESIS-2, a de-identified minimal dataset can be obtained. Information about NEMESIS-2 data can be requested by contacting the principal investigator of NEMESIS-2: Dr. Margreet ten Have: firstname.lastname@example.org.
Funding: JES is employed at the Topclinical Centre for Body, Mind and Health, GGz Breburg and Tilburg University. MH is employed at the Netherlands Institute of Mental Health and Addiction. CR is employed at the Department of Residency training, GGz Breburg. HM is employed at VU University medical centre and at Centre for Primary Care, Institution of Population Health, University of Manchester. RG is employed at the Netherlands Institute of Mental Health and Addiction. CFC is employed at the Topclinical Centre for Body, Mind and Health, GGz Breburg and Tilburg University. CFC received grants from the EU FP7 programme, Achmea Social Insurance Company, Netherlands Organisation for Scientific Research (NWO), Eli Lilly, GGz Ingeest, Arkin, Dutch Ministry of Health, the Netherlands Organisation for Health Research and Development (ZonMw) and European Science Foundation. CFC received royalties for books on psychiatry. CFC received money for lectures from Eli Lilly. The employers/funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Co-author Christina van der Feltz-Cornelis is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. Christina van der Feltz-Cornelis reported grants from Eli Lilly, NIHR, EU FP7 program, ZonMw, and Achmea outside the submitted work. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials, except those mentioned in the data availability statement.
Medically Unexplained Symptoms (MUS) are highly prevalent in primary care [1–11], occupational health care  and specialist care . They are associated with serious dysfunction such as disability in the workplace [6–8, 12, 14, 15] and high health care use [12, 14–16]. They often co-occur with common mental disorders like major depressive disorder, generalised anxiety disorder and panic disorder in primary care and in the occupational setting [12, 17, 18]; however, their specific recognition and treatment have been low [19–24]. The co-occurrence of MUS in depressive or anxiety disorders leads to a less favourable treatment response [25–31] and consequently to frequent health care use, disability and increased costs .
Definitions of MUS vary widely, depending on the setting [2, 5, 7, 18, 32–34]. In primary care, prevalence rates range from 1.5% to 11% depending on whether or not the criteria are restrictive [7, 35]. In general hospital settings, specific patterns of MUS are often called functional somatic syndromes, like fibromyalgia, chronic fatigue and irritable bowel syndrome, and appear to show a marked relationship with depression and anxiety [13, 36], presenting in up to 25% of patients with a depressive, anxiety or somatoform disorder in one study .
In the general population, a high prevalence rate (11.8%) is found for the presence of ‘any depression or anxiety disorder’ for subjects with MUS . However, it is unknown to what extent the presence of MUS is a predictor of the development of depression and anxiety. Furthermore, from clinical practice, we know that comorbid substance use disorder can be an additional problem in subjects with MUS, but this has not been researched yet. Therefore, the aim of this project was to estimate prevalence and incidence rates of depression, anxiety and substance use disorder in relation to MUS in a large general population cohort, i.e. the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2) [38, 39].
MUS versus explained physical symptoms
During the diagnostic medical process, physical symptoms may remain ‘unexplained’ but they may also be explained by actual physical illnesses. Escobar et al. found that both explained and unexplained physical symptoms are equally strongly associated with depression and anxiety in a cross-sectional study in a community setting . However, this question has not been explored at the population level, and also, substance use disorder has not been taken into account. Furthermore, the question arises whether there is a difference between MUS and explained physical symptoms (PHY) with regard to the development of comorbid mental disorders in the long run. Additionally as a third question, these prevalence and incidence rates so far have not been explored in patients with combined explained and unexplained symptoms, although having a combination of the two might be difficult to cope with for a patient and could potentially give rise to mental disorders as well. An unfavourable course of mental disorder in the presence of physical symptoms has been described [25–27]. If individuals in the general population in the MUS, PHY or MUS+PHY groups would more often develop mental disorders over time than the control group, it would suggest that more attention should be given to the detection and treatment of these mental disorders, in order to diminish the burden of disease.
The objectives of this study are:
To measure prevalence and incidence rates of mood disorder, anxiety and substance use disorder in subjects with MUS compared to those with PHY or a combination of MUS and PHY.
To explore prevalence and incidence rates of comorbid mood, anxiety and substance use disorder among subjects in the general population in a control group with no explained physical symptoms and no MUS (NONE), a group with explained physical symptoms only (PHY), a group with MUS only and a group with both MUS and explained physical symptoms (MUS+PHY).
We hypothesize that the prevalence rates of mood disorder, anxiety disorder and substance use disorder are higher in the groups of respondents with MUS only, PHY only or both MUS and PHY compared to those with no physical symptoms (control respondents). We hypothesize that the effect is biggest in the combined MUS + PHY group, because of the abovementioned difficulties that arise for the patient in coping with the combination of unexplained and explained physical symptoms, and for the physician in diagnosing and managing the concomitant symptoms properly. Furthermore, we hypothesize that the same reasons apply for the incidence rates in the respective groups.
For this study, we used data from NEMESIS-2, a nationally representative face-to-face survey held with subjects aged 18–64 at baseline, interviewed twice (once in 2007–2009 and another time in 2010–2012) with the Composite International Diagnostic Interview (CIDI) 3.0 . NEMESIS-2 was approved by the Medical Ethics Review Committee for Institutions on Mental Health Care (METIGG). Respondents provided written informed consent to participate in the interview, after full written and verbal information about the study was given before and at the start of the baseline assessment.
Setting and participants
Nationally representative population based study. As described by de Graaf et al. , this study was conducted as follows:
For the first wave (T0), in a multistage, stratified random sampling procedure, a random sample of 184 of the 443 existing municipalities was drawn. In these municipalities, a random sample of addresses of private households was drawn from postal registers. Based on the most recent birthday at first contact within the household, an individual aged 18–64 with sufficient fluency in the Dutch language was randomly selected for a face-to-face interview.
The response rate of the first wave was 65.1%. The sample was nationally representative, although younger subjects were somewhat underrepresented .
For the second wave (T1), all 6,646 participants were approached for follow-up, three years after baseline, of which 5,303 could be interviewed again (80.4% response, excluding those who were deceased).
The mean period between both interviews was 3 years and 7 days (1,102 days; sd = 64). At T1, there was a significantly higher chance of attrition with lower age and lower educational level. Attrition was also more likely if respondents were unemployed or born outside the Netherlands. No differences were found for gender, cohabitation status, urbanicity and having a chronic physical disorder .
Of the total group of 6,646 baseline respondents, 140 respondents received a shortened version of the interview, and as a consequence did not receive questions about somatic disorders. Therefore, the number of respondents in the analyses for the prevalence research question was 6,506.
Definition of Medically Unexplained Symptoms.
For this study, we use the following definition of MUS: presence of one or more physical symptom(s) in the past 12 months for which no adequate organ pathology or pathophysiological basis was found, and for which, according to the subject, a physician was consulted and/or medication was received, and which caused discomfort and functional impairment in the past 4 weeks as measured by the Short Form 36 (SF-36) [7, 33, 42, 43].
We included the presence of discomfort and functional impairment in the definition, to stay in line with the Somatoform disorders in DSM-IV  and the DSM-5 Somatic Symptom Disorder , that both require discomfort and functional impairment. SSD is ‘characterized by somatic symptoms that are either very distressing or result in significant disruption of functioning, as well as excessive and disproportionate thoughts, feelings and behaviours regarding those symptoms. The individual must be persistently symptomatic (typically at least for six months) .
Quantitative variables and study size
Operationalisation of four groups.
We distinguished the following groups: firstly, respondents with no MUS and no explained physical symptoms comprised the control group (NONE, n = 4168). Secondly, respondents with explained physical symptoms only, which were the physical symptoms in the checklist minus those symptoms we considered to be MUS, were defined as (PHYonly, n = 1952). Thirdly, those who had MUS, but no physical symptoms that were explained by physical disorders were grouped as MUSonly (n = 177). The final, most complex group included those who had both MUS and explained physical symptoms (MUS+PHY, n = 209).
All analyses were performed with STATA version 11, using weighted data to correct for differences in the response rates of several socio-demographic groups (sex, age, partner status, employment situation, education) at both waves, and differences in the probability of the selection of respondents within households at baseline. Robust standard errors were calculated in order to obtain correct 95% confidence intervals and p-values .
For the demographic variables analysis, summary statistics were used to describe the socio-demographic characteristics of the abovementioned four groups of subjects with and without MUS: NONE, PHYonly, MUSonly and MUS+PHY.
For the analysis of prevalence rates, 12-month prevalence rates of comorbid mental disorders among these groups were calculated and multivariate logistic regression analyses were used to examine the association between group membership and the prevalence of comorbid mental disorders, adjusted for all abovementioned socio-demographic characteristics. Odds Ratios and 95% confidence intervals were presented. In the logistic regression analyses, the NONE group was used as the reference group. In additional analyses, we varied the reference group to examine the extent to which the groups with physical symptoms (PHYonly, MUSonly and MUS+PHY) differed in their odds of having and developing mental disorders.
For the analysis of incidence rates, first-incidence rates of mental disorders among these groups were calculated and multivariate logistic regression analyses were used to examine the association between group membership and incidence of comorbid mental disorders, adjusted for socio-demographic characteristics. Odds Ratios and 95% confidence intervals were presented. In the logistic regression analyses, the NONE group was used as the reference group.
Table 2 describes the socio-demographic characteristics of the abovementioned four groups: NONE (n = 4168), PHYonly (n = 1932), MUSonly (n = 177), MUS+PHY (n = 209).
There were significant differences between the groups regarding the following socio-demographic variables:
More women than men had physical symptoms, either explained or unexplained.
Although the majority had a partner, subjects in the MUS group were more often single.
The groups with explained symptoms had a significantly higher mean age than MUSonly, who were represented in all age groups above 24 years at similar levels.
80.3% of people in the control group had a paid job, while the employment rate in the MUS+PHY group was only 50.3%.
31.0% of the control group had a higher professional/university education, versus 18.1% in the MUS+PHY group, and around 25% in both the PHYonly and MUSonly groups.
Outcome data and main results
Table 3 describes the 12-month prevalence and odds ratios (ORs) of mood, anxiety and substance use disorders in the four abovementioned groups. In all groups, anxiety disorder was more common than mood and substance use disorders.
Compared to the NONE group, the MUS+PHY group showed consistently elevated ORs for the prevalence of mood disorder, anxiety disorder and substance use disorder, which mainly consisted of alcohol abuse and dependence.
Compared to the NONE group, both the PHYonly group and the MUSonly group showed significantly elevated ORs for mood disorder and anxiety disorder, but not for substance use disorder. The ORs for prevalence were the highest in the MUSonly group.
When PHYonly, MUSonly and MUS+PHY were respectively used as the reference group, the only significant difference was that MUS+PHY showed a higher OR for substance use disorder when compared to PHYonly. However, this does not change the general direction of our results.
The 3-year incidence rates and ORs of mood disorder, anxiety and substance use disorder are reported in Table 4. Because first-incidence rates were calculated, the number at risk varied per mental disorder: for mood disorder n = 4098, for anxiety disorder n = 4113, for substance use disorder n = 4326.
Compared to the NONE group, there are no significant differences in incidence rates for mood disorder, anxiety disorder or substance disorder in PHYonly and MUSonly. The only significant incidence rate occurred in the MUS+PHY group for mood disorders compared to the NONE group, OR 2.92(1.27,6.74).
When PHYonly, MUSonly and MUS+PHY were respectively used as the reference group, the only significant difference was that MUS+PHY showed a higher OR for mood disorder when compared to PHYonly. However, this does not change the general direction of our results.
The first main finding in this study was that our first hypothesis was confirmed. The MUS+PHY group showed an elevated prevalence of mood disorder, anxiety disorder and alcohol use disorder compared to the control group. For both PHY only and MUS only, the prevalence rate of mood disorder and anxiety disorder was significantly higher than in the control group. Compared to previous studies, this provides us with new information. Firstly, this is because our study was conducted in the general population instead of in a selected group of subjects, such as in primary care [1–8, 10–11], general hospital settings [13, 32] or in the workplace [8, 12, 14, 15]. Secondly, it is because those studies only concerned subjects with MUS and no comparison was made with subjects with PHY or combined MUS plus PHY. Thirdly, this is the first study that also takes alcohol abuse and dependence into account. The fact that the prevalence is highest in the combined group emphasizes the importance of proper diagnosis and management of this combination of symptoms and prioritizes this even above MUSonly and PHYonly. Dealing with the complexity of combined MUS and PHY seems to be difficult.
The second main finding is that our second hypothesis, which states that incidence rates would be elevated as well, and mostly in the MUS+PHY group, was confirmed for mood disorder. Thus, again, the group with combined MUS and PHY seems to be the most vulnerable of the three groups that were studied, in the long term. The incidence of mental disorders in the three groups has not been studied so far, and this finding suggests that concomitant unexplained and explained physical symptoms place the highest burden on patients and should be a specific focus of attention. This finding provides fodder for the new category in DSM-5, Somatic Symptom Disorder, that does not consider the explained or unexplained nature of the symptoms to be the crux criterion, but the distress and functional impairment that coincides with it. Future research should certainly focus on better diagnosis and treatment approaches for this patient group.
Regarding socio-demographic variables, our findings were similar to the studies in the clinical settings reporting on MUS , and explained physical symptoms . We found that more women had physical symptoms than men, both explained and unexplained. This suggests that no particular demographic bias exists in terms of comparing findings from clinical settings to findings from the general population As would be expected, older people had more explained physical symptoms. However, all age groups above 24 years of age had only MUS to similar levels. In a recent review, comparable prevalence rates were found for MUS in a younger and middle age group, although wide ranges were reported . Employment rates were the lowest in those with MUS only and those with both MUS and explained symptoms. This may be an indication of the level of dysfunction in both groups; this rate is somewhat higher than in the group with physical symptoms alone, as was previously established in a comparison between patients with rheumatoid arthritis and somatisation .
To our knowledge, the incidence rates of mental disorders among MUS cases as well as explained physical symptoms in the general population have not previously been studied. Our findings provide us with the opportunity to gain insight into a question that often arises in clinical practice, namely whether or not MUS precede depressive and anxiety symptoms and substance use disorder. The finding that one in every ten subjects with combined MUS and explained physical symptoms develops a mood disorder in three years time indeed suggests that subjects with the combination of explained and unexplained physical symptoms require extra attention to recognise and treat imminent mood disorders.
A strength of this study is that it provides new findings regarding the incidence of mood, anxiety and substance use disorder in subjects with medically explained, unexplained and combined physical symptoms.
As we used an existing database, we divided the sample retrospectively into four groups based on pre-defined clinical criteria. Although we had this limitation, we believe that our methods of operationalisation and classification are reasonable for MUS. We combined the presence of one or more medically unexplained physical symptom(s) with the presence of limited functioning, and thereby we approach essential criteria for distress and functional impairment that apply both in the DSM-IV somatoform disorders as well as the Somatic Symptom Disorder as described in the DSM 5.
Our findings show a clear burden of depressive, anxiety and substance abuse or dependence disorder in the three groups of physical symptoms at the level of the general population. Our findings also show that the highest burden of disease occurs in the group of subjects with both MUS and PHY, which is the most difficult to treat. To explain to a patient that some of his or her physical symptoms can be medically explained, but other symptoms may not, can be a challenge. In view of the elevated incidence of mood disorder in this group, further research should therefore focus on treatment strategies for this specific group, with a special focus on greater attention for the development of an explanation model that both the physician and the patient can support. This can prevent the increasing insecurity and depressive symptoms that could result from the physical symptoms. Another treatment strategy could be to ensure good management of the treatment, such as paying attention to the course of the physical symptoms and regularly monitoring patients for mental problems, in a case management and disease management approach as has been suggested i.e. in the Multidisciplinary Guideline for Medically Unexplained Symptoms and Somatoform Disorders . In this approach, collaboration between primary and secondary care by psychiatric consultation models, or a more elaborate model known as transmural collaborative care, is of interest [17, 60, 61]. Consultation models with the occupational health physician may be necessary as well, because of the apparent negative influence that MUS have on employment and positive outcomes in terms of Return To Work [62, 63]. However, although these models have been described and been shown to be effective in clinical research, their implementation should probably be improved. Research is needed to explore further treatment needs of these patients, as well as implementation and organizational needs of their doctors. Mental problems can also precede MUS, which is something we did not study here, but is a subject of interest for further research.
An important strength of NEMESIS-2 is that it is a large nationally representative sample of the adult Dutch general population. Therefore, the results can be extrapolated to the general population of the Netherlands, and possibly to a wider area.
In the general population, PHY, MUS and the combination of both are related to mood and anxiety disorders, but odds are highest for combined MUS and PHY in relation to substance use disorder. Combined MUS and PHY are related to a greater incidence of mood disorder. These findings warrant further research into possibilities to improve recognition and early intervention in subjects with combined MUS with PHY.
NEMESIS-2 is conducted by the Netherlands Institute of Mental Health and Addiction (Trimbos Institute) in Utrecht. Financial support has been received from the Ministry of Health, Welfare and Sport, with supplementary support from the Netherlands Organization for Health Research and Development (ZonMw) and the Genetic Risk and Outcome of Psychosis (GROUP) investigators.
Conceived and designed the experiments: JES MH CR HM RG CFC. Performed the experiments: JES MH RG CFC. Analyzed the data: MH. Wrote the paper: JES MH CR HM RG CFC.
- 1. Arnold IA, de Waal MW, Eekhof JA, Assendelft WJ, Spinhoven P, van Hemert AM. Medically unexplained physical symptoms in primary care: a controlled study on the effectiveness of cognitive-behavioral treatment by the family physician. Psychosomatics. 2009;50(5):515–24. pmid:19855038
- 2. Arnold IA, de Waal MW, Eekhof JA, van Hemert AM. Somatoform disorder in primary care: course and the need for cognitive-behavioral treatment. Psychosomatics. 2006;47(6):498–503. pmid:17116951
- 3. de Waal MW, Arnold IA, Eekhof JA, Assendelft WJ, van Hemert AM. Follow-up study on health care use of patients with somatoform, anxiety and depressive disorders in primary care. BMC Fam Pract. 2008;9:5. pmid:18218070
- 4. de Waal MW, Arnold IA, Spinhoven P, Eekhof JA, van Hemert AM. The reporting of specific physical symptoms for mental distress in general practice. Journal of psychosomatic research. 2005;59(2):89–95. pmid:16186004
- 5. de Waal MW, Arnold IA, Eekhof JA, van Hemert AM. Somatoform disorders in general practice: prevalence, functional impairment and comorbidity with anxiety and depressive disorders. The British journal of psychiatry: the journal of mental science. 2004;184:470–6. pmid:15172939
- 6. Steinbrecher N, Koerber S, Frieser D, Hiller W. The prevalence of medically unexplained symptoms in primary care. Psychosomatics. 2011;52(3):263–71. pmid:21565598
- 7. Swanson LM, Hamilton JC, Feldman MD. Physician-based estimates of medically unexplained symptoms: a comparison of four case definitions. Fam Pract. 2010;27(5):7.
- 8. Kroenke K, Spitzer RL, Williams JB, Linzer M, Hahn SR, deGruy FV 3rd, et al. Physical symptoms in primary care. Predictors of psychiatric disorders and functional impairment. Arch Fam Med. 1994;3(9):774–9. pmid:7987511
- 9. Escobar JI, Cook B, Chen CN, Gara MA, Alegria M, Interian A, et al. Whether medically unexplained or not, three or more concurrent somatic symptoms predict psychopathology and service use in community populations. Journal of psychosomatic research. 2010;69(1):1–8. pmid:20630257
- 10. Allen LA, Gara MA, Escobar JI, Waitzkin H, Silver RC. Somatization: a Debilitating Syndrome in Primary Care. Psychosomatics. 2001;42(1):63–7. pmid:11161123
- 11. Bair MJ, Wu J, Damush TM, Sutherland JM, Kroenke K. Association of depression and anxiety alone and in combination with chronic musculo-skeletal pain in primary care patients. Psychosomatic medicine. 2008;70(8):890–7. pmid:18799425
- 12. Hoedeman R, Krol B, Blankenstein N, Koopmans PC, Groothoff JW. Severe MUPS in a sick-listed population: a cross-sectional study on prevalence, recognition, psychiatric co-morbidity and impairment. BMC Public Health. 2009;9:440. pmid:19951415
- 13. Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosomatic medicine. 2003;65(4):528–33. pmid:12883101
- 14. Hoedeman R, Blankenstein AH, Krol B, Koopmans PC, Groothoff JW. The contribution of high levels of somatic symptom severity to sickness absence duration, disability and discharge. J Occup Rehabil. 2010;20(2):264–73. pmid:20373134
- 15. Hoedeman R, Krol B, Blankenstein AH, Koopmans PC, Groothoff JW. Sick-listed employees with severe medically unexplained physical symptoms: burden or routine for the occupational health physician? A cross sectional study. BMC Health Serv Res. 2010;10:305. pmid:21059232
- 16. Konnopka A, Schaefert R, Heinrich S, Kaufmann C, Luppa M, Herzog W, et al. Economics of medically unexplained symptoms: a systematic review of the literature. Psychotherapy and psychosomatics. 2012;81(5):265–75. pmid:22832397
- 17. van der Feltz-Cornelis CM, van Oppen P, Ader HJ, van Dyck R. Randomised controlled trial of a collaborative care model with psychiatric consultation for persistent medically unexplained symptoms in general practice. Psychotherapy and psychosomatics. 2006;75(5):282–9. pmid:16899964
- 18. van der Feltz-Cornelis CM, van Balkom AJ. The concept of comorbidity in somatoform disorder—a DSM-V alternative for the DSM-IV classification of somatoform disorder. Journal of psychosomatic research. 2010;68(1):97–9; author reply 9–100. pmid:20004307
- 19. Kroenke K, Jackson JL, Chamberlin J. Depressive and anxiety disorders in patients presenting with physical complaints: clinical predictors and outcome. Am J Med. 1997;103(5):339–47. pmid:9375700
- 20. Simon GE, Vonkorff M, Piccinelli M, Fullerton C, Ormel J. An international study of the relation between somatic symptoms and depression. N Eng J Med. 1999;341(18):1329–35. pmid:10536124
- 21. Mergl R, Seidscheck I, Allgaier AK, Möller HJ, Hegerl U, Henkel V. Depressive, anxiety, and somatoform disorders in primary care: prevalence and recognition. Depress Anxiety. 2007;24(3):185–95. pmid:16900465
- 22. Verhaak PF, Prins MA, Spreeuwenberg P, Draisma S, van Balkom TJ, Bensing JM, et al. Receiving treatment for common mental disorders. General hospital psychiatry. 2009;31(1):46–55. pmid:19134510
- 23. Schulberg HC. Treating depression in primary care practice: applications of research findings. J Fam PRACT. 2001;50(6):535–7. pmid:11401741
- 24. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity. Arch Intern Med. 2003;163(20):2433–45. pmid:14609780
- 25. Huijbregts KM, van der Feltz-Cornelis CM, van Marwijk HW, de Jong FJ, van der Windt DA, Beekman AT. Negative association of concomitant physical symptoms with the course of major depressive disorder: a systematic review. Journal of psychosomatic research. 2010;68(6):9.
- 26. Huijbregts KM, van Marwijk HW, de Jong FJ, Schreuders B, Beekman AT, van der Feltz-Cornelis CM. Adverse effects of multiple physical symptoms on the course of depressive and anxiety symptoms in primary care. Psychotherapy and psychosomatics. 2010;79(6):389–91. pmid:20829652
- 27. Huijbregts KM, de Jong FJ, van Marwijk HW, Beekman AT, Ader HJ, van der Feltz-Cornelis CM. A high physical symptom count reduces the effectiveness of treatment for depression, independently of chronic medical conditions. Journal of psychosomatic research. 2013;74(3):179–85. pmid:23438706
- 28. Papakostas GI, Petersen TJ, Iosifescu DV, Summergrad P, Sklarsky BA, Alpert JE, et al. Somatic symptoms as predictors of time to onset of response to fluoxetine in major depressive disorder. J Clin Psychiatry. 2004;65(4):543–6. pmid:15119918
- 29. Papakostas GI, Petersen T, Denninger J, Sonnawalla SB, Mahal Y, Alpert JE, et al. Somatic symptoms in treatment-resistant depression. Psychiatry Res. 2003;118(1):39–45. pmid:12759160
- 30. Papakostas GI, McGrath P, Stewart J, Charles D, Chen Y, Mischoulon D, et al. Psychic and somatic anxiety symptoms as predictors of response to fluoxetine in major depressive disorder. Psychiatry Res. 2008;161(1):116–20. pmid:18755514
- 31. Keeley RD, Smith JL, Nutting PA, Miriam DL, Perry DW, Rost KM. Does a depression intervention result in improved outcomes for patients presenting with physical symptoms? J Gen Intern Med. 2004;19(6):615–23. pmid:15209599
- 32. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing; 2013.
- 33. Rosendal M FP, Falkoe E, Schou Hansen H, Olesen F. Improving the Classification of Medically Unexplained Symptoms in Primary Care. Eur J Psychiat. 2007;21:25–36.
- 34. Dimsdale JE. Somatic Symptom Disorders: a new approach in DSM-5. Die psychiatrie. 2013;10:30–2.
- 35. Körber S FD, Steinbrecher N, Hiller W. Classification characteristics of the Patient Health Questionnaire-15 for screening somatoform disorders in a primary care setting. Journal of psychosomatic research. 2011;71:142–7. pmid:21843748
- 36. Burton C, McGorm K, Weller D, Sharpe M. Depression and anxiety in patients repeatedly referred to secondary care with medically unexplained symptoms: a case-control study. Psychol Med. 2011;41(3):555–63. Epub 2011/01/29. pmid:21272387
- 37. Rosmalen J.G.M. TLM, de Jonge P. Empirical foundation for the diagnosis of somatization: implications for DSM-5. Psychol Med. 2010;41:1133–42. pmid:20843407
- 38. de Graaf R, Ten Have M, van Dorsselaer S. The Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2): design and methods. Int J Methods Psychiatr Res. 2010;19(3):125–41. pmid:20641046
- 39. de Graaf R, ten Have M, van Gool C, van Dorsselaer S. Prevalence of mental disorders and trends from 1996 to 2009. Results from the Netherlands Mental Health Survey and Incidence Study-2. Soc Psychiatry Psychiatr Epidemiol. 2012;47(2):203–13. pmid:21197531
- 40. Haro JM, Arbabzadeh-Bouchez S, Brugha TS, de Girolamo G, Guyer ME, Jin R, et al. Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health surveys. Int J Methods Psychiatr Res. 2006;15(4):167–80. pmid:17266013
- 41. De Graaf R, van Dorsselaer S, Tuithof M, ten Have M. Sociodemographic and psychiatric predictors of attrition in a prospective psychiatric epidemiological study among the general population. Result of the Netherlands Mental Health Survey and Incidence Study-2. Comprehensive Psychiatry. 2013;54:1131–9. pmid:23810078
- 42. Brazier JE, Harper R, Jones NM, O'Cathain A, Thomas KJ, Usherwood T, et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. Bmj. 1992;305(6846):160–4. pmid:1285753
- 43. Aaronson NK, Muller M, Cohen PD, Essink-Bot ML, Fekkes M, Sanderman R, et al. Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. J Clin Epidemiol. 1998;51(11):1055–68. pmid:9817123
- 44. Association AP. Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC2000.
- 45. Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, et al. Sampling and methods of the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl. 2004(420):8–20. pmid:15128383
- 46. De Graaf R, Ormel J, Ten Have M. Mental disorders and service use in The Netherlands. Results from the Eruoopean Study of the Epidemiology of Mental Disorders (ESEMeD). In: Kessler RC, Üstün TB, editors. The WHO World Mental Health Surveys Global Perspectives on the Epidemiology of Mental Disorders. New York: Cambridge University Press; 2008. p. 388–405.
- 47. de Graaf R, Ten Have M, Tuithof M, van Dorsselaer S. First-incidence of DSM-IV mood, anxiety and substance use disorders and its determinants: Results from the Netherlands Mental Health Survey and Incidence Study-2. J Affect Disord. 2013.
- 48. Andrews G, Peters L. The psychometric properties of the Composite International Diagnostic Interview. Soc Psychiatry Psychiatr Epidemiol. 1998;33(2):80–8. pmid:9503991
- 49. Wittchen HU. Reliability and validity studies of the WHO—Composite International Diagnostic Interview (CIDI): a critical review. J Psychiatr Res. 1994;28(1):57–84. pmid:8064641
- 50. CBS vademecum. "CBS vragenlijst chronische ziekten". 2005.
- 51. Baker MM, Stabile M., Deri C. What do self-reported, objective measures of health measure? NBER Working paper series. 2001.
- 52. Knight M, Stewart-Brown S, Fletcher L. Estimating health needs: the impact of a checklist of conditions and quality of life measurement on health information derived from community surveys. J Public Health Med. 2001;23(3):179–86. pmid:11585189
- 53. National Center for Health Statistics. Evaluation of national health interview survey diagnostic reporting. Series 2: Data evaluation and methods research1994.
- 54. Guthrie E, Thompson D. Abdominal pain and functional gastrointestinal disorders. Bmj. 2002;325(7366):701–3. pmid:12351366
- 55. Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain? Jama. 1992;268(6):760–5. pmid:1386391
- 56. Skinner CJ, Holt D, Smith TMF. Analysis of Complex Surveys. Chichester: Willey; 1989.
- 57. Centraal Bureau voor de Statistiek. 'Gezondheid en zorg in cijfers'. Den Haag/Heerlen: 2012.
- 58. Hilderink PH, Collard R, Rosmalen JGM, Oude Voshaar RC. Prevalence of somatoform disorder and medically unexplained symptoms in old age polpulations in comparison with younger age groups: A systematic review. Ageing res rev. 2013;12(1):151–6. pmid:22575906
- 59. van der Feltz-Cornelis CM, Swinkels JA, Blankenstein AH, Hoedeman R, Keuter EJ, stoornissen WSke. (The Dutch multidisciplinary guideline entitled 'Medically unexplained physical symptoms and somatoform disorder'). Ned Tijdschr Geneeskd. 2011;155((18)A1244. Dutch.). pmid:21429250
- 60. Walker EA, Keegan D, Gardner G, Sullivan M, Katon WJ, Bernstein D. Psychosocial Factors in Fibromyalgia Compared With Rheumatoid Arthritis: I. Psychiatric Diagnoses and Functional Disability. Psychosomatic medicine. 1997;59(6):565–71. pmid:9407573
- 61. Volker D, Vlasveld MC, Anema JR, Beekman AT, Hakkaart- van Roijen L, Brouwers EP, et al. Blended E-health module on return to work embedded in collaborative occupational health care for common mental disorders: design of a cluster randomized trial. Neuropsychiatric disease and treatment. 2013;9:529–37. pmid:23637534
- 62. Van der Feltz-Cornelis CM, Hoedeman R, De Jong FJ, Meeuwissen JA, Drewes HW, Van der Laan NC, et al. Faster return to work after psychiatric consultation for sicklisted employees with common mental disorders compared to care as usual. A randomized clinical trial. Neuropsychiatric disease and treatment. 2010;7(6):375–85.
- 63. van der Feltz-Cornelis CM, Meeuwissen JA, De Jong FJ, Hoedeman R, Elfeddali I. Randomised controlled trial of a psychiatric consultation model for treatment of common mental disorder in the occupational health setting. BMC Health Serv Res. 2007 27(7).