Depression, anxiety, and somatic complaints: is it all psychosomatic?

Hans-Ulrich WITTCHEN, PhD
Franziska EINSLE, PhD
Institute for Clinical Psychology and Psychotherapy
Center of Clinical Epidemiology and Longitudinal Studies (CELOS)
Dresden University of Technology

Depression, anxiety, and somatic complaints: is it all psychosomatic?

by H.-U. Wittchen and F. Einsle, Germany

Anxiety, depression, and somatic complaints are strongly interrelated core concepts describing a wide range of subjective verbal expressions that may range from transient negative affect expressions to those associated with enduring prototypical clinically relevant mental disorders. Within a wider conceptualization of a biopsychosocial disease concept, referred to by the problematic umbrella term “psychosomatics,” this review selectively presents strong evidence that somatic and mental disorders overlap heavily. Therefore, both disorders share, with some variation in the diagnostic area, a wide variety of vulnerability and risk factors relevant to diagnosis, treatment, and prognosis. Although recent reconceptualizations of the diagnostic classification of mental disorders have improved research, knowledge of the complex multifactorial interplay of somatic and mental disorders still remains largely deficient, particularly with regard to identification of the involved causal mechanisms. It is necessary to understand these putative complex reciprocal relationships in order to develop improved, more effective treatment strategies in patients with comorbid mental and somatic disorders.

Medicographia. 2012;34:307-314 (see French abstract on page 314)

Traditional diagnostic classification systems like the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10)1 separate mental disorders from somatic diseases as though there are clear boundary lines. It is generally accepted that this separation is artificial, not appropriately reflecting the apparent mind-body continuum, and even clinically unfortunate, as there might be as much of a somatic component in mental disease as there is a mental component in somatic disease. The situation is complicated by the term “psychosomatic.” This term entails different meanings and connotations ranging from disputed concepts of psychoanalysis and psychogenesis of diseases2 over multifactorial models of illness (known as the biopsychosocial model3) to modern concepts denoting psychosomatics as a comprehensive, interdisciplinary framework.4 Modern definitions of psychosomatics require assessment of psychological and behavioral factors as well as a consideration of biopsychosocial factors in clinical routine.4 Besides this, modern psychosomatics should use evaluated and integrated psychological interventions not only in treatment, but also in prevention and rehabilitation.4 Depending on this conceptual focus, the term “behavioral medicine” is preferred by psychological and behavioral researchers as a term that more clearly separates their work from traditional psychodynamic conceptions (Figure 1, page 308).

Figure 1
Figure 1. The modern concept of psychosomatics and matched with the current diagnostic concepts of ICD-10 and DSM-IV-TR.

Abbreviations: DSM-IV-TR, Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision; ICD-10, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Since the implementation of descriptive diagnostic classes and explicit diagnostic criteria in the Diagnostic and Statistical Manual for Mental Disorders (DSM),5 the idea that diseases are multicausal or psychosomatic in the modern sense has implicitly been adopted by highlighting the need for multiaxial classification and emphasizing the concept of comorbidity of, at least, mental disorders. In comparison with older classification systems, this more descriptive and atheoretical approach does not use the term psychosomatics, but suggests that all patients should be classified according to diagnostic classes of mental disorders (axis 1), the presence of personality disorders (axis 2), the presence of somatic diseases (axis 3), the presence of psychosocial precipitants (axis 4), and the current psychosocial functioning status (axis 5). However, it is fair to state that this stringent multiaxial classification approach has never received overwhelming acceptance both in research and practice. Furthermore, this approach has a number of drawbacks, eg, diagnosis being categorical and not dimensional. It is nevertheless notable that the DSM classification has considerably inspired concept development in research and practice; in particular, concerning a broad range of studies examining the associations between mental and somatic disease with regard to etiopathology and care.

Coverage and scope

Within this perspective, this paper selectively reviews evidence about the associations between defined somatic and mental disorders, focusing on the prognostic impact of mental disorders on physical health and somatic treatment. It should be mentioned that the current knowledge base does not allow more than a simple description of associations. A more detailed clarification of the dynamic interrelationships over time as well as the determination of causal mechanisms is currently not feasible. There is an extremely large number of studies that have examined the association of mental disorders, including anxiety, depressive and somatoform disorders, and somatic illness. This paper focuses on some common somatic illnesses, namely coronary heart disease (CHD), myocardial infarction (MI), diabetes, cancer, and other chronic “somatic” conditions (eg, asthma), as it is not possible to review all studies about the association of mental and somatic disorders. We considered including the vast array of studies about mental disorders and pain syndromes6-8 (eg, headache, back pain), but discarded this initial idea because pain is a syndrome that cannot easily be classified as being somatic or mental.9 We also do not deal explicitly with somatoform syndromes, because of the unclear and much disputed nosological status of these conditions10 and ongoing discussions of their diagnostic reconceptualization.

Association of mental and somatic disorders in community and primary care

Gureje recently provided the most comprehensive and detailed epidemiologic evidence of associations between mental and somatic disorders adjusted for age and gender based on community samples in the World Mental Health Surveys (Table I).7 Because anxiety, mood disorders, and somatic disease are highly prevalent and thus might co-occur because of their frequency simply by chance, the associations are corrected by chance agreement using the odds ratio (OR). Overall, and controlling for chance agreement, Gureje found that there are substantial associations with anxiety or mood disorders, but not for all somatic diseases.7 The strongest associations between mood and anxiety disorders were found for heart disease. Additional analyses showed that the associations are consistent across different cultures and similar both in developing and developed countries.

These results are in line with previous study findings from the ZARADEMP Project (ZARAgoza-DEMentia-dePression)11 and the Canadian Community Health Survey,12 both based on samples with older adults (>55 years of age). In the study of Lobo-Escolar et al,11 the association between somatic diseases and mental disorders had an overall OR of 1.61 (95% confidence interval [CI], 1.38-1.88), controlled for age, gender, and education. Interestingly, the association diminished when including hypertension (OR=0.85; 95% CI, 0.71-1.02).11 The study by El-Gabalawy et al showed that gastrointestinal and lung disease had the highest associations with anxiety and not heart disease.12 Although the vast majority of community studies do not report findings for cancer, Greer et al,13 based on data from the US National Comorbidity Study Replication (NCS-R), showed that long-term cancer survivors suffer more often from anxiety disorder (OR=1.49; 95%CI, 1.04-2.13), especially specific phobia (OR=1.59; 95% CI, 1.06-2.44) and medical (eg, blood injury) phobia (OR=3.45; 95% CI, 1.15- 10.0) than those without cancer histories.

Table I
Table I. Age- and sex-adjusted
odds ratios for mental disorders
(12-month prevalence)
among persons with asthma,
diabetes, heart disease, and

Modifed from reference 7: Gureje.
In: Von Korff MR, Scott KM, Gureje
O, eds. Global Perspectives on Mental-
Physical Comorbidity in the WHO
World Mental Health Surveys. New
York, NY: Cambridge University Press;
2009:56. © 2009, World Health

In primary care samples, where patients are randomly picked among primary care attenders, results appear at first glance to be different from those for community samples. For example, in the DETECT study (Diabetes cardiovascular risk Evaluation: Targets and Essential data for Commitment of Treatment), with over 50 000 primary care patients, depression rates were significantly, though moderately, elevated for almost all conditions examined, when not adjusted for the number of somatic conditions (Table II, Model 1, page 310).14 As previously addressed in community surveys, hypertension was one of the few somatic conditions without significant associations. However, when adjusted for the number of somatic comorbid conditions, only few remained significant, namely cancer (OR=1.5), some specific heart diseases (OR=1.3-1.5), stroke (OR=1.6-1.8), gastrointestinal diseases and hepatitis (OR=1.2-1.4), as well asmusculoskeletal diseases (OR=1.3).14

Most importantly, the DETECT study highlighted that the risk of comorbid depression is substantial and increased from an OR of 1.6 to 6.2 with the number of comorbid conditions (Figure 2, page 311).14 This suggests that somatic morbidity may be affected by behavior, such as demoralization, making it much more prevalent than it would be due to an individual somatic condition alone.

Prevalence of mental disorders in cancer and cardiac samples

Given the consistent findings of associations between somatic disease with anxiety and/or depression,7 it is not surprising to see that these patterns have received substantial clinical research attention, especially for the most common diseases such as cancer and cardiac disease.When searching for publications using the Web of Science database for the years 1990 to 2012, 13 535 results can be found for “anxiety and disease” and 37 655 for “depression and disease.”

Table II
Table II. Prevalence and associations of depression and different somatic diseases in a primary care setting (DETECT).

Abbreviations: CI, confidence interval; DETECT, Diabetes cardiovascular risk Evaluation: Targets and Essential data for Commitment of Treatment; DSQ, depression
screening questionnaire; N, number; OR, odds ratio; TIA/PRIND, transient ischemic attack/ prolonged reversible ischemic neurologic deficit.
Modifed from reference 14: Pieper et al. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2008;51(4):411-421. © 2008, Springer Medizin Verlag.

Reviews point out that for cardiovascular disease (CVD) 15% to 20% of patients15 suffer from depressive disorders; among cancer patients, the median prevalence was 16.5% (95% CI, 13.1-20.3).16 This constitutes, in comparison with community surveys, a 2- to 3-fold increase in the risk of depression. In both domains, clinical research on comorbid depression has strongly focused on deriving clinically useful typologies, underlying mechanisms, and implications of these substantial associations. For example, a current research question in cancer patients concerns the distinction between “true” depression versus cancer-related fatigue17,18 which might mimic depression, as well as the underlying psychosocial and neurobiological pathways involved, and respective treatment implications. Similarly, in CVD-depression research, the role of reciprocal pathways in etiology and the complication role of depression for the course of CVD and premature mortality and treatment implications have been emphasized and will be reported later in this review.

Regarding anxiety disorders, the clinical research focus has shifted from generic measures of anxiety to studying the impact of specific anxiety (eg, panic and generalized anxiety disorder) and stress-related disorders. In recent years, for example, Spindler and Pedersen19 discussed the role of trauma and posttraumatic stress disorder (PTSD) in patients with cardiac diseases, and Kangas, Henry, and Bryant20 their role in cancer patients. Both reviews highlight the problematic definition of what constitutes a traumatic event in medical settings. Traumas in medical settings differ from others because the stressor is internally induced, and the effect of the stressor mostly lies in the future.20 Hence, to clarify the impact of PTSD in medical settings, more research about specific definitions of trauma in this context, as well as a differentiation from adjustment disorders, is necessary.

The impact of anxiety and depression on physical health and its treatment

There is strong evidence that a comorbid anxiety and/or depressive disorder negatively affects the severity and the outcome of somatic disease.21 Measured dimensionally, patients with somatic disease and comorbid mental disorders report a significantly decreased physical and mental quality of life in comparison with somatically ill persons without mental disorders, independent of type of somatic disease and mental disorder.22

In addition to quality of life, another problematic topic associated with mental disorders is noncompliance, which includes nonadherence to medical treatments and no reduction in behavioral risk factors, such as smoking.23 For example, the DETECT study showed that, in patients with type 2 diabetes, depression at baseline predicts problematic medication compliance aswell as unsatisfactory glycemic control at follow-up.24

Figure 2
Figure 2. Odds ratios (ORs) for depression as a function of the
number of comorbid somatic diseases.
OR adjusted for age and gender.

Modified from reference 14: Pieper et al. Bundesgesundheitsblatt Gesundheitsforschung
Gesundheitsschutz. 2008;51(4):411-421. © 2008, Springer Medizin

Fichter et al25 pointed out that comorbidity of mental disorders increases mortality risk in somatically ill patients. These results have been confirmed, especially with regard to impact of depression on mortality risk. For example, comorbid depression is associated with an at least 2-fold increased risk of mortality in patients with heart disease.26,27 Patients with diabetes and comorbid depression also have an increased risk for higher disability and mortality.8,28,29 Meta-analyses by Satin et al30 and Pinquart and Duberstein31 show that patients with cancer and major or minor depression have a 1.19 to 1.35 higher mortality risk than patients without comorbid depression. Mortality risk is increased not only by severe depressive symptoms, as even minimal subthreshold depressive symptoms have an independent effect on mortality.32 There is also evidence of a higher mortality risk in anxiety disorders, but results are inconsistent. As an example of a “positive” association, mortality rate was significantly higher in patients with a transplantation-related PTSD.33 It is possible that this finding resulted from worse compliance in these patients,19 or the fact that PTSD itself is predictive of poor outcome. There may be a need to consider the course of anxiety symptoms over time in order to better predict medical outcomes.34

These results show the impact of mental disorders on physical health risks in particular. However, it is unclear to what degree the treatment of a mental disorder affects mental symptoms and somatic risks. Different reviews35,36 have summarized that psychological treatments in general have been shown to reduce depression and improve quality of life in cardiac patients. The benefit with respect to improved clinical outcomes has not been conclusively demonstrated. The literature available on treatment of anxiety in patients with somatic disease is quite restricted. Some studies20,37,38 report a decrease in anxiety symptoms, but likely due to the focus of treatments on depression, no improvement of somatic factors. It is a problem that in somatically ill patients, the focus is commonly on symptoms and unspecific treatments, instead of disorders and specific interventions. Still, unspecific psychological treatment might be useful in patients with somatic disease. For example, independent of other prognostic factors, mortality risk in women with CHD decreased after participation in group-based psychosocial intervention (eg, SWITCHD study39 [Stockholm Women’s Intervention Trial for CHD]). All in all, uncertainty remains if there are subgroups of patients (eg, regarding age, gender, and social background) that benefit more from psychological treatments than others. Besides this, the question to ask appears to be what ingredients are needed for successful intervention. Whalley et al36 have reported 4 predictors regarding the success of interventions for depression: i) having an aim to treat type-A behaviors, ii) having an aim to educate about cardiac risk factors, iii) inclusion of client-led discussion and emotional support, and iv) inclusion of family members in the process.

Processes to explain the association of mental disorders and somatic disease

The mechanisms for the association between mental and physical disorders remain understudied. Most of the research in this area focuses on the effect of depression on chronic physical conditions, especially heart diseases. Nevertheless, two causal perspectives are conceivable.

_ From mental disorders to somatic disease
There is more evidence that mental disorders are predictors for the development of somatic diseases than vice versa.21 Depression and/or anxiety predicted the development of CHD,40 cerebrovascular disease,41 and asthma42 in several studies. Moreover, Scott et al43 reported that patients with comorbid anxiety-depression disorders had stronger associations with physical disease than patients with a single mental disorder. To explain this finding, a potential mechanism being discussed is a greater adrenocorticotropic hormone (ACTH) response in patients with comorbid anxiety-depression.44,45 For the biological pathway, “stress” is a plausible explanation: depression and anxiety go along with changes in the autonomic nervous system (including the sympathetic adrenal medullary [SAM] axis and hypothalamus-pituitary-adrenal [HPA] axis).46,47 Such dysregulations are also associated with changes in the immune, cardiovascular, and metabolic systems.21 Regarding somatic diseases in patients with mental disorders, the behavioral pathway is based on increased risk behavior, like smoking, binge eating, or lack of exercise.21,48 The behavioral pathway also includes the problem of reduced compliance for medical treatments (as addressed above under the section “The impact of anxiety and depression on physical health and its treatment”) as well as the modification of behavioral risk factors (eg, commencement of sports activities) in patients with mental disorders.21

_ From physical disease to mental disorder
The other direction—from somatic disease to mental disorder— is under-researched. This might be explained by the fact that most patients with somatic disease do not fulfill the criteria of a mental disorder.49 Nevertheless, there is evidence that persons with a somatic disease, like type 2 diabetes, have an increased risk of developing incident depression.50 One possible process explaining why so many stay mentally healthy after a severe somatic disease was reported by Leventhal et al,51 suggesting that people seek information for a better understanding of the development and course of their somatic disease and to be able to cope with the critical situation. Besides this, it may be assumed that factors associated with the development of psychological disorders in general also play a role in patients with somatic diseases.52 Thus, a chronic physical disorder can be seen as a stressor or critical life event and therefore play a role in vulnerability-stress models about the development of mental disease. For example, disability and constraints due to a somatic disease increase the risk of depression’s onset.53 Also, social consequences of chronic diseases, like loss of amplifiers, affect the risk for later mental disorders.21 Furthermore, increased attention has recently been paid to the multitude of direct and indirect neurobiological pathways.21 There, physical disorders go along with endocrine, metabolic, as well as immunological changes leading to symptoms of anxiety or depression.

_ Bidirectionality and shared risk factors
Focusing on only one direction from somatic to mental or from mental to somatic, might be too narrow.21 As described, depression increases the risk for CHD as well as diabetes.40,54 The somatic disorder itself goes along with disability and loss of amplifiers and can therefore intensify the depression.21 Hence, the concept of bidirectionality is important for understanding the association of mental and physical disorders. Similarly, it is well established that anxiety is typically a primary, and most frequently lifelong, disorder starting in childhood and adolescence, associated with increased risk of temporally secondary depression. Because of this highly complex interplay of various system components, the assumption of common shared risk factors and core etiopathogenic pathways is certainly the most promising way forward.21,55 Corresponding studies showed that early childhood adversities produce vulnerabilities not only for mental disorders, but also somatic diseases56,57 and suggest that enduring changes in the regulation of the HPA axis is a potential common pathway. However, there are additional factors, such as socioeconomic status, whose impact on the association between mental and somatic disease is under discussion.58


Anxiety, depression, and somatic complaints are strongly interrelated core concepts describing a wide range of subjective verbal expressions that may range from transient negative affect expressions to those arising from enduring prototypical clinically relevant mental disorders.Within a wider conceptualization of a biopsychosocial disease concept, referred to by the problematic umbrella term “psychosomatics”, this review selectively presents strong evidence that somatic and mental disorders overlap heavily. Therefore, both disorders share a wide variety of vulnerability and risk factors relevant for diagnosis, treatment and prognosis, with some variation in the diagnostic area. Although recent reconceptualizations of the diagnostic classification of mental disorders have improved research, the complex multifactorial interplay of somatic and mental disorders still remains largely undefined, particularly with regard to elucidation of the causal mechanisms. It is necessary to understand these putative complex reciprocal relationships in order to develop improved and more effective treatment strategies in patients with comorbid mental and somatic disorders. _

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Keywords: anxiety; chronic disease; comorbidity; depression; prevalence