The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care

Abstract:

BACKGROUND: Depression, anxiety and fatigue are among the most common symptoms presented in primary care. Whether such symptoms indicate discrete psychological syndromes or whether they result from a common vulnerability is not clear. This study examined longitudinally the patterns of co-morbidity between prolonged fatigue and other forms of psychological distress in patients attending general practitioners.

METHODS: Adults attending primary care completed questionnaires designed to detect cases of prolonged fatigue and psychological distress at presentation and 12 months later.

RESULTS: Of 652 patients, the prevalence rates of ‘prolonged fatigue’ alone, ‘psychological distress’ alone, ‘prolonged fatigue + psychological distress’ and ‘no disorder’ were 7%, 19%, 15% and 59% respectively at initial assessment. Of those patients with any prolonged fatigue syndrome initially, 58% still reported fatigue 12 months later (representing 13% of the total sample). Most importantly, the risk of developing prolonged fatigue was not increased in patients who initially had psychological distress (OR = 0.95; 95% CI 0.2-3.6), neither was the risk of developing psychological distress increased in patients who initially had prolonged fatigue (OR = 1.4; 95% CI 0.6-3.4).

CONCLUSIONS: This study indicates that prolonged fatigue is a persistent diagnosis over time. The longitudinal patterns of co-morbidity with psychological distress do not support an aetiological model that proposes a common vulnerability factor for these disorders. Psychiatric classification systems may be better served by treating prolonged fatigue and psychological distress as independent disorders.

 

Source: Hickie I, Koschera A, Hadzi-Pavlovic D, Bennett B, Lloyd A. The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care. Psychol Med. 1999 Jul;29(4):855-61. http://www.ncbi.nlm.nih.gov/pubmed/10473312

 

Unique genetic and environmental determinants of prolonged fatigue: a twin study

Abstract:

BACKGROUND: Prolonged fatigue syndromes have been proposed as prevalent and disabling forms of distress that occur independently of conventional notions of anxiety and depression.

METHODS: To investigate the genetic and environmental antecedents of common forms of psychological and somatic distress, we measured fatigue, anxiety, depression and psychological distress in 1004 normal adult twin pairs (533 monozygotic (MZ), 471 dizygotic (DZ)) over 50 years of age.

RESULTS: Familial aggregation of psychological distress, anxiety and fatigue appeared to be due largely to additive genetic factors (MZ:DZ ratios of 2.12-2.69). The phenotypic correlations between the psychological measures (distress, anxiety and depression) were moderate (0.67-0.79) and higher than that between fatigue and psychological distress (0.38). Multivariate genetic modelling revealed a common genetic factor contributing to the development of all the observed phenotypes (though most strongly for the psychological forms), a second independent genetic factor also influenced anxiety and depression and a third independent genetic factor made a major contribution to fatigue alone. In total, 44% (95% CI 25-60%) of the genetic variance for fatigue was not shared by the other forms of distress. Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor.

CONCLUSION: This study supports the aetiological independence of prolonged fatigue and, therefore, argues strongly for its inclusion in classification systems in psychiatry.

 

Source: Hickie I, Kirk K, Martin N. Unique genetic and environmental determinants of prolonged fatigue: a twin study. Psychol Med. 1999 Mar;29(2):259-68. http://www.ncbi.nlm.nih.gov/pubmed/10218917

 

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

 

The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue

Abstract:

Past studies have shown that severe fatigue was the presenting symptom in six of seven patients with delayed orthostatic hypotension and that tilt table-induced hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We have determined the prevalence of fatigue, volunteered in response to a nonspecific pre-examination questionnaire used in 431 patients, each subsequently diagnosed as having one of eight neurological or endocrine disorders.

The results show that fatigue is a very common symptom in patients with delayed orthostatic hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106) hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7-33% in all groups, and was intermediate in prevalence in patients with acute hyperadrenergic orthostatic hypotension (n = 32): 41%.

It is concluded that fatigue commonly results from delayed orthostatic hypotension and all forms of hypocortisolism but is less common in patients with acute orthostatic hypotension, both idiopathic and due to MSA, which more commonly present with lightheadedness or syncope.

 

Source: Streeten DH, Anderson GH Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. 1998 Apr;8(2):119-24. http://www.ncbi.nlm.nih.gov/pubmed/9613802

 

The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study

Abstract:

OBJECTIVES: This study examined the prevalence and public health impact of chronic fatigue and chronic  fatigue syndrome in primary care patients in England.

METHODS: There were 2376 subjects, aged 18 through 45 years. Of 214 subjects who fulfilled criteria for chronic fatigue, 185 (86%) were interviewed in the case-control study. Measures included chronic fatigue, psychological morbidity, depression, anxiety, somatic symptoms, symptoms of chronic fatigue syndrome, functional impairment, and psychiatric disorder.

RESULTS: The point prevalence of chronic fatigue was 11.3%, falling to 4.1% if comorbid psychological disorders were excluded. The point prevalence of chronic fatigue syndrome was 2.6%, falling to 0.5% if comorbid psychological disorders were excluded. Rates did not vary by social class. After adjustment for psychological disorder, being female was modestly associated with chronic fatigue. Functional impairment was profound and was associated with psychological disorder.

CONCLUSIONS: Both chronic fatigue and chronic fatigue syndrome are common in primary care patients and represent a considerable public health burden. Selection bias may account for previous suggestions of a link with higher socioeconomic status.

 

Source: Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Public Health. 1997 Sep;87(9):1449-55. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1380968/ (Full article)

 

Chronic fatigue syndrome. A practical guide to assessment and management

Abstract:

Chronic fatigue and chronic fatigue syndrome (CFS) have become increasingly recognized as a common clinical problem, yet one that physicians often find difficult to manage. In this review we suggest a practical, pragmatic, evidence-based approach to the assessment and initial management of the patient whose presentation suggests this diagnosis. The basic principles are simple and for each aspect of management we point out both potential pitfalls and strategies to overcome them.

The first, and most important task is to develop mutual trust and collaboration. The second is to complete an adequate assessment, the aim of which is either to make a diagnosis of CFS or to identify an alternative cause for the patient’s symptoms. The history is most important and should include a detailed account of the symptoms, the associated disability, the choice of coping strategies, and importantly, the patient’s own understanding of his/her illness. The assessment of possible comorbid psychiatric disorders such as depression or anxiety is mandatory.

When the physician is satisfied that no alternative physical or psychiatric disorder can be found to explain symptoms, we suggest that a firm and positive diagnosis of CFS be made.

The treatment of CFS requires that the patient is given a positive explanation of the cause of his symptoms, emphasizing the distinction among factors that may have predisposed them to develop the illness (lifestyle, work stress, personality), triggered the illness (viral infection, life events) and perpetuated the illness (cerebral dysfunction, sleep disorder, depression, inconsistent activity, and misunderstanding of the illness and fear of making it worse).

Interventions are then aimed to overcoming these illness-perpetuating factors. The role of antidepressants remains uncertain but may be tried on a pragmatic basis. Other medications should be avoided. The only treatment strategies of proven efficacy are cognitive behavioral ones. The most important starting point is to promote a consistent pattern of activity, rest, and sleep, followed by a gradual return to normal activity; ongoing review of any ‘catastrophic’ misinterpretation of symptoms and the problem solving of current life difficulties.

We regard chronic fatigue syndrome as important not only because it represents potentially treatable disability and suffering but also because it provides an example for the positive management of medically unexplained illness in general.

 

Source: Sharpe M, Chalder T, Palmer I, Wessely S. Chronic fatigue syndrome. A practical guide to assessment and management. Gen Hosp Psychiatry. 1997 May;19(3):185-99. http://www.ncbi.nlm.nih.gov/pubmed/9218987

 

Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition.

METHODS: Assays for soluble interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination.

RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01).

CONCLUSION: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CFS and CF.

 

Source: Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol. 1997 Feb;24(2):372-6. http://www.ncbi.nlm.nih.gov/pubmed/9034999

 

Chronic fatigue syndrome criteria in patients with other forms of unexplained chronic fatigue

Abstract:

To determine the prevalence of chronic fatigue syndrome (CFS) criteria in other forms of unexplained chronic fatigue, 297 consecutive outpatients under the age of 40 from a general medicine practice were studied. After excluding the three with chronic fatigue syndrome, the remaining 294 individuals were divided into those with unexplained chronic fatigue (64 patients) those without (the remaining 230 patients).

Chronic fatigue syndrome criteria noted to be significantly more common in those with unexplained fatigue compared to those without include: fever, painful adenopathy, muscle weakness, myalgia, headache, migratory arthralgia, neuropsychologic symptoms, and sleep disorder. Like chronic fatigue syndrome, unexplained chronic fatigue often started suddenly.

I conclude that the CFS criteria are noted more commonly than expected in other forms of unexplained chronic fatigue.

 

Source: Chester AC. Chronic fatigue syndrome criteria in patients with other forms of unexplained chronic fatigue. J Psychiatr Res. 1997 Jan-Feb;31(1):45-50. http://www.ncbi.nlm.nih.gov/pubmed/9201646

 

Screening for psychiatric disorders in chronic fatigue and chronic fatigue syndrome

Abstract:

Psychiatric disorders are common in chronic fatigue (CF) and chronic fatigue syndrome (CFS). To determine the usefulness of the General Health Questionnaire (GHQ), a self-report measure of psychological distress, in identifying those with psychiatric illnesses, a structured psychiatric interview and the GHQ were administered to 120 CF and 161 CFS patients seen in a referral clinic.

Overall, 87 (35%) patients had a current and 210 (82%) a lifetime psychiatric disorder. Compared to patients without psychiatric disorders, GHQ scores above the threshold (> or = 12) were more frequent among patients with current (p < 0.001) and lifetime (p < 0.05) diagnoses; scores among patients with CF and CFS were similar.

Longer illness duration, greater fatigue severity, and current psychiatric disorders were significant predictors of the GHQ score. In CF and CFS, the best sensitivity (0.69-0.76) and specificity (0.51-0.62) were achieved for current psychiatric diagnoses using a threshold score of > or = 12. Thus, patients scoring < 12 on the GHQ are significantly less likely to have a psychiatric disorder.

 

Source: Buchwald D, Pearlman T, Kith P, Katon W, Schmaling K. Screening for psychiatric disorders in chronic fatigue and chronic fatigue syndrome. J Psychosom Res. 1997 Jan;42(1):87-94. http://www.ncbi.nlm.nih.gov/pubmed/9055216

 

Prevalence of irritable bowel syndrome in chronic fatigue

Abstract:

The aetiologies of irritable bowel syndrome and chronic fatigue are unknown. Psychological as well as physical factors have been implicated in both. Fatigue is common in irritable bowel syndrome patients. The purpose of the study was to determine the prevalence of irritable bowel syndrome in chronic fatigue sufferers.

A bowel symptom questionnaire was sent to all 4,000 members of a self-help group for fatigue sufferers. Of the 1,797 who responded, 1,129 (63%) fulfilled a diagnosis of irritable bowel syndrome (recurrent abdominal pain and at least three Manning criteria). This greatly exceeds estimates of irritable bowel syndrome prevalence of up to 22% in the general population.

Furthermore, irritable bowel syndrome sufferers within this chronic fatigue population reported more Manning criteria (14% had all six Manning criteria) than irritable bowel syndrome sufferers in the general population. This study demonstrates an overlap of symptoms in chronic fatigue and irritable bowel syndrome. In chronic fatigue, irritable bowel symptoms may be one aspect of a more generalised disorder.

 

Source: Gomborone JE, Gorard DA, Dewsnap PA, Libby GW, Farthing MJ. Prevalence of irritable bowel syndrome in chronic fatigue. J R Coll Physicians Lond. 1996 Nov-Dec;30(6):512-3. http://www.ncbi.nlm.nih.gov/pubmed/8961203