Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review

Abstract:

OBJECTIVE: Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior.

METHODS: A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study.

RESULTS: Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression.

CONCLUSIONS: Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as “common mental disorders” does not seem fully appropriate.

 

Source: Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003 Jul-Aug;65(4):528-33. http://www.ncbi.nlm.nih.gov/pubmed/12883101

 

Chronic fatigue syndrome

Comment on:

Chronic fatigue syndrome. [Br J Gen Pract. 2001]

Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study. [Br J Gen Pract. 2001]

 

Professor Murdoch in the September BJGP 1 uses his study of Down’s syndrome,2 which demonstrated that mothers had an increased number of reported illnesses in the year before the birth, to undermine our interpretation of the findings in our chronic fatigue syndrome (CFS) study in the July BJGP. 3 He asks why anyone should believe CFS is caused by behavioural factors.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314178/pdf/11766858.pdf

 

Source: Hamilton W. Chronic fatigue syndrome. Br J Gen Pract. 2001 Dec;51(473):1015. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314178/pdf/11766858.pdf (Full comment)

 

Chronic fatigue syndrome

Comment in: Chronic fatigue syndrome. [Br J Gen Pract. 2001]

Comment on: Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study. [Br J Gen Pract. 2001]

 

The study of Hamilton et al in the July issue of the BJGP, 1 claims that a higher consultation rate in people with chronic fatigue syndrome (CFS) before they develop the diagnosis supports the hypothesis that behavioural factors have a role in its aetiology. A similar case-control study of mothers and fathers of Down’s syndrome children showed that both mothers and fathers had significantly more recorded illnesses before the birth of the child and that the mothers had significantly more psychosis, neurosis or self-poisoning.2

The problem with such findings is deciding what they mean. No-one would suggest that Down’s syndrome is caused by ‘behavioural factors,’ so why should anyone believe that of CFS? There is no more evidence that increased frequency of attendance before diagnosis points to behavioural factors in CFS than that it points to non-dysjunction in the germ cells of mothers of Down’s syndrome children.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314117/pdf/11593850.pdf

 

Source: Murdoch JC. Chronic fatigue syndrome. Br J Gen Pract. 2001 Sep;51(470):758. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314117/pdf/11593850.pdf (Full comment)

 

Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) research has concentrated on infective, immunological, and psychological causes. Illness behaviour has received less attention, with most research studying CFS patients after diagnosis. Our previous study on the records of an insurance company showed a highly significant increase in illness reporting before development of CFS.

AIM: To investigate the number and type of general practitioner (GP) consultations by patients with CFS for 15 years before they develop their condition.

DESIGN OF STUDY: Case-control study in 11 general practices in Devon.

SETTING: Forty-nine patients with CFS (satisfying the Centers for Disease Control criteria), 49 age, sex, and general practice matched controls, and 37 patients with multiple sclerosis (MS) were identified from the general practices’ computerised databases.

METHOD: The number of general practice consultations and symptoms recorded in three five-year periods (quinquennia) were counted before development of the patients’ condition.

RESULTS: The median number of consultations was significantly higher for CFS patients than that of matched controls in each of the quinquennia: ratios for first quinquennium = 1.88, P = 0.01; second quinquennium = 1.70, P = 0.005; last quinquennium = 2.25, P < 0.001. More CFS patients than controls attended for 13 of the 18 symptoms studied. Significant increases were found for upper respiratory tract infection (P < 0.001), lethargy (P < 0.001), and vertigo (P = 0.02). Similar results were found for CFS patients when compared with MS.

CONCLUSIONS: CFS patients consulted their GP more frequently in the 15 years before development of their condition, for a wide variety of complaints. Several possibilities may explain these findings. The results support the hypothesis that behavioural factors have a role in the aetiology of CFS.

Comment in:

Chronic fatigue syndrome. [Br J Gen Pract. 2001]

Chronic fatigue syndrome. [Br J Gen Pract. 2001]

 

Source: Hamilton WT, Hall GH, Round AP. Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study. Br J Gen Pract. 2001 Jul;51(468):553-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314047/ (Full article)

 

Significant other responses are associated with fatigue and functional status among patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: The predictive power of partners’ responses to illness behavior for illness outcomes was investigated among couples in which one person had chronic fatigue syndrome (CFS).

METHODS: One hundred nineteen participants who met case-definition criteria for CFS and were living with a significant other (SO) completed self-report measures of relationship satisfaction, responses of their SO to fatigue symptoms, and outcome measures of fatigue and functional status.

RESULTS: The results indicated that more frequent solicitous SO responses to illness behavior were predictive of greater fatigue-related severity and bodily pain. Solicitous SO responses to fatigue behavior were particularly influential in the context of a satisfactory relationship. In highly satisfactory relationships, solicitous SO responses were associated with significantly greater fatigue severity and fatigue-related disability than in relationships characterized by low or average satisfaction.

CONCLUSIONS: Solicitous SO responses to CFS-related symptoms are associated with poorer patient outcomes, especially in the context of a satisfactory intimate relationship. Because of the cross-sectional nature of the study, the direction of effects cannot be interpreted unambiguously. SOs may be inadvertently positively reinforcing illness-related behavior: Solicitous partners may help the patient more with tasks of daily living, thereby decreasing the patient’s activity level, which may lead to deconditioning and disability. Alternatively, patients with more severe symptoms and disability may present more opportunities for concerned SO responses, which again may be heightened in the context of a caring, satisfactory relationship. In either case, the results suggest that additional research on the role of solicitous SO responses is warranted.

 

Source: Schmaling KB, Smith WR, Buchwald DS. Significant other responses are associated with fatigue and functional status among patients with chronic fatigue syndrome. Psychosom Med. 2000 May-Jun;62(3):444-50. http://www.ncbi.nlm.nih.gov/pubmed/10845358

 

Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue

Abstract:

Chronic fatigue syndrome, which can occur after acute infection and last for years, is characterized by severe and persistent fatigue. Others have reported decreases in mouse running activity following infection and have suggested this may provide an animal model for studying chronic fatigue.

Voluntary running is a highly motivated activity in mice, which will often run 5-7 mi/day in our laboratory. Following 2 weeks of acclimation to running wheels with food and water available ad lib, female BALB/c mice received 0.2-mL tail vein injections of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on voluntary running and grooming behavior were determined.

Injection of BA caused an immediate large decrease in running and a lack of grooming. Vehicle injections produced no changes in behavior. After the first several days of reduced running behavior, levels of running and grooming slowly returned back to normal over the next 2-4 weeks, with substantial individual differences in the rate of recovery.

The pattern of running during recovery was intriguing in that BA mice first ran at normal levels just after the lights went out, but they stopped after only 1-2 h. As recovery proceeded, they gradually increased the duration of the running bout during the night. Because this model uses voluntary exertion and the ability to run for longer periods of time characterizes recovery, the model may be a good one for studying the biologic underpinnings of chronic fatigue.

 

Source: Ottenweller JE, Natelson BH, Gause WC, Carroll KK, Beldowicz D, Zhou XD, LaManca JJ. Mouse running activity is lowered by Brucella abortus treatment: a potential model to study chronic fatigue. Physiol Behav. 1998 Mar;63(5):795-801. http://www.ncbi.nlm.nih.gov/pubmed/9618001

 

Coping with chronic fatigue syndrome: illness responses and their relationship with fatigue, functional impairment and emotional status

Abstract:

The implications of patients’ approaches to managing chronic fatigue syndrome were examined in a cross-sectional study. With severity of fatigue controlled, attempting to maintain activity was associated with less functional impairment, while accommodating to the illness was positively related to impairment; behavioural disengagement was related not only to higher levels of impairment but also to greater emotional disturbance. Fatigue itself was positively associated with focusing on symptoms and with behavioural disengagement; it was associated also with illness accommodation, but only for illness of longer duration. The causal direction of relationships between coping and fatigue severity is ambiguous, and a follow-up study will address the effects of coping on changes in the illness over time.

 

Source: Ray C, Jefferies S, Weir WR. Coping with chronic fatigue syndrome: illness responses and their relationship with fatigue, functional impairment and emotional status. Psychol Med. 1995 Sep;25(5):937-45. http://www.ncbi.nlm.nih.gov/pubmed/8588012

 

Are cytokines associated with neuropsychiatric syndromes in humans?

Abstract:

Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals.

In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS).

Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illness, systemic autoimmune diseases and chronic fatigue syndrome).

Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed.

We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.

 

Source: Hickie I, Lloyd A. Are cytokines associated with neuropsychiatric syndromes in humans? Int J Immunopharmacol. 1995 Aug;17(8):677-83. http://www.ncbi.nlm.nih.gov/pubmed/8847162

 

“Abnormal” illness behaviour in chronic fatigue syndrome and multiple sclerosis

Abstract:

OBJECTIVE: To investigate the presence of abnormal illness behaviour in patients with a diagnosis of chronic fatigue syndrome.

DESIGN: A cross sectional descriptive study using the illness behaviour questionnaire to compare illness behaviour scores and illness behaviour profiles of patients with chronic fatigue syndrome and patients with multiple sclerosis.

SETTING: A multidisciplinary fatigue clinic and a teaching hospital neurology outpatient clinic.

SUBJECTS: 98 patients satisfying the Oxford criteria for chronic fatigue syndrome and 78 patients with a diagnosis of multiple sclerosis.

MAIN OUTCOME MEASURE: Responses to the 62 item illness behaviour questionnaire.

RESULTS: 90 (92%) patients in the chronic fatigue syndrome group and 70 (90%) in the multiple sclerosis group completed the illness behaviour questionnaire. Both groups had significantly high scores on the general hypochondriasis and disease conviction subscales and significantly low scores on the psychological versus somatic concern subscale, as measured in relation to normative data. There were, however, no significant differences in the subscale scores between the two groups and the two groups had identical illness behaviour profiles.

CONCLUSION: Scores on the illness behaviour questionnaire cannot be taken as evidence that chronic fatigue syndrome is a variety of abnormal illness behaviour, because the same profile occurs in multiple sclerosis. Neither can they be taken as evidence that chronic fatigue and multiple sclerosis share an aetiology. More needs to be known about the origins of illness beliefs in chronic fatigue syndrome, especially as they are important in determining outcome.

Comment in:

Illness behaviour in the chronic fatigue syndrome and multiple sclerosis. Choice of multiple sclerosis as comparison condition was inappropriate.[BMJ. 1995]

Illness behaviour in the chronic fatigue syndrome and multiple sclerosis. Disentangling common characteristics is not so easy. [BMJ. 1995]

 

Source: Trigwell P, Hatcher S, Johnson M, Stanley P, House A. “Abnormal” illness behaviour in chronic fatigue syndrome and multiple sclerosis. BMJ. 1995 Jul 1;311(6996):15-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550080/pdf/bmj00599-0019.pdf (Full article)

 

Does high ‘action-proneness’ make people more vulnerable to chronic fatigue syndrome? A controlled psychometric study

Abstract:

Degree of premorbid ‘action-proneness’ was measured, using a self-administered questionnaire, in 35 patients suffering from chronic fatigue syndrome (CFS), all the members of ‘ME’-self help groups and all those meeting CDC-criteria of CFS. The results were compared with those of 30 chronic idiopathic musculoskeletal pain patients, 34 patients with a chronic organic condition, and 34 neurotic patients without primary somatic complaints. Statistical analysis showed that CFS patients described themselves as significantly more ‘action-prone’ than the last two groups, and to a degree which was comparable with the chronic pain group. The results could not be explained by concomitant depression and are in accordance with anecdotal reports of premorbid hyperactive lifestyle in CFS patients. Further investigations seem worthwhile to test the hypothesis that hyperactivity might be a predisposing factor for chronic illness behaviour in CFS patients.

 

Source: Van Houdenhove B, Onghena P, Neerinckx E, Hellin J. Does high ‘action-proneness’ make people more vulnerable to chronic fatigue syndrome? A controlled psychometric study. J Psychosom Res. 1995 Jul;39(5):633-40. http://www.ncbi.nlm.nih.gov/pubmed/7490698