Electrodermal dissociation of chronic fatigue and depression: evidence for distinct physiological mechanisms

Abstract:

Chronic fatigue syndrome (CFS) has an estimated prevalence between 0.5% and 3%, yet its diagnosis remains contentious. CFS is characterized by subjective symptoms that can be difficult to verify; moreover, depression is a commonly reported CFS complaint, whereas fatigue is a common symptom of depression.

Our primary goal was dissociation of these disorders using psychophysiological methods. As previous research has implicated the autonomic nervous system in CFS, we conducted what we believe to be the first analysis of bilateral electrodermal and skin temperature responses of dextral females in a cross-modal orienting task, to investigate differences between these two patient groups and controls.

A multivariate analysis of variance (MANOVA) examining three measures of electrodermal activity revealed prestimulus tonic skin conductance levels (SCLs) were markedly lower for the CFS group, with no difference between controls and depressives. Concurrent skin temperature levels were higher for the CFS group than the other two groups.

These findings indicate that, despite overtly similar cognitive and symptom profiles, depression and CFS patients can be differentiated with psychophysiological measures. This study adds to the growing body of evidence demonstrating that CFS and depression have distinct neurobiological profiles, consistent with unique aetiologies.

Copyright 2004 Elsevier B.V.

 

Source: Pazderka-Robinson H, Morrison JW, Flor-Henry P. Electrodermal dissociation of chronic fatigue and depression: evidence for distinct physiological mechanisms. Int J Psychophysiol. 2004 Aug;53(3):171-82. http://www.ncbi.nlm.nih.gov/pubmed/15246671

 

Dysautonomias: clinical disorders of the autonomic nervous system

Abstract:

The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities.

In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after “patchy” autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops.

Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with beta-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology.

 

Source: Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G. Dysautonomias: clinical disorders of the autonomic nervous system. Ann Intern Med. 2002 Nov 5;137(9):753-63. http://www.ncbi.nlm.nih.gov/pubmed/12416949

 

Chronic fatigue syndrome: a hypothesis focusing on the autonomic nervous system

Abstract:

Chronic fatigue syndrome is a debilitating illness of unknown aetiology, with estimated levels of prevalence of up to about 8. 7/100 000 in the U.S.A. Like pain fatigue it is a personal, emotionally rich experience, which may originate from peripheral or central sites (or both). The nature of the symptoms is complex and reflects the interaction of the patient with the environment and cultural milieu. Accordingly the common use of the same terminology for different types of fatigue may be misleading.

Autonomic activation is a key component of both real and simulated physical exercise. Alterations in autonomic nervous system activity are a key component of several physiopathological conditions. In chronic fatigue syndrome disturbances in autonomic activity, and in other homoeostatic mechanisms, such as the hormonal and immune systems, have been reported recently.

In this review we followed the hypothesis that in chronic fatigue syndrome the paradoxical condition of disturbing somatic symptoms in the absence of organic evidence of disease might be addressed by focusing on attending functional correlates. In particular we addressed possible alterations in cardiovascular autonomic control, as can be assessed by spectral analysis of R-R interval and systolic arterial pressure variability.

With this approach, in subjects complaining of unexplained fatigue, we obtained data suggesting a condition of prevailing sympathetic modulation of the sino-atrial node at rest, and reduced responsiveness to excitatory stimuli. Far from considering the issue resolved, we propose that in the context of the multiple physiological and psychological interactions involved in the perception and self-reporting of symptoms, attendant changes in physiological equivalents might furnish a convenient assessment independent from subjective components.

Indices of sympathetic modulation could, accordingly, provide quantifiable signs of the interaction between subject’s efforts and environmental demands, independently of self descriptions, which could provide convenient measurable outcomes, both for diagnosis and treatment titration in chronic fatigue syndrome.

Comment in: Long- and short-term blood pressure and RR-interval variability and psychosomatic distress in chronic fatigue syndrome. [Clin Sci (Lond). 1999]

 

Source: Pagani M, Lucini D. Chronic fatigue syndrome: a hypothesis focusing on the autonomic nervous system. Clin Sci (Lond). 1999 Jan;96(1):117-25. http://www.ncbi.nlm.nih.gov/pubmed/9857114

 

Does the chronic fatigue syndrome involve the autonomic nervous system?

Abstract:

PURPOSE: To investigate the role of the autonomic nervous system in the symptoms of patients with chronic fatigue syndrome (CFS) and delineate the pathogenesis of the orthostatic Intolerance and predisposition to neurally mediated syncope reported in this patient group.

PATIENTS AND METHODS: Twenty-three CFS patients and controls performed a battery of autonomic function tests. The CFS patients completed questionnaires pertaining to autonomic and CFS symptoms, their level of physical activity, and premorbid and coexisting psychiatric disorders. The relationship between autonomic test results, cardiovascular deconditioning, and psychiatric disorders was examined with multivariate statistics and the evidence that autonomic changes seen in CFS might be secondary to a postviral, idiopathic autonomic neuropathy was explored.

RESULTS: The CFS subjects had a significant increase in baseline (P < 0.01) and maximum heart rate (HR) on standing and tilting (both P < 0.0001). Tests of parasympathetic nervous system function (the expiratory inspiratory ratio, P < 0.005; maximum minus minimum HR difference, P < 0.05), were significantly less in the CFS group as were measures of sympathetic nervous system function (systolic blood pressure decrease with tilting, P < 0.01; diastolic blood pressure decrease with tilting, P < 0.05; and the systolic blood pressure decrease during phase II of a Valsalva maneuver, P < 0.05). Twenty-five percent of CFS subjects had a positive tilt table test. The physical activity index was a significant predictor of autonomic test results (resting, sitting, standing, and tilted HR, P < 0.05 to P < 0.009); and the blood pressure decrease in phase II of the Valvalsa maneuver, P < 0.05) whereas premorbid and coexistent psychiatric conditions were not. The onset of autonomic symptoms occurred within 4 weeks of a viral infection in 46% of patients-a temporal pattern that is consistent with a postviral, idiopathic autonomic neuropathy.

CONCLUSION: Patients with CFS show alterations in measures of sympathetic and parasympathetic nervous system function. These results, which provide the physiological basis for the orthostatic intolerance and other symptoms of autonomic function in this patient group, may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both.

 

Source: Freeman R, Komaroff AL. Does the chronic fatigue syndrome involve the autonomic nervous system? Am J Med. 1997 Apr;102(4):357-64. http://www.ncbi.nlm.nih.gov/pubmed/9217617

 

The rise and fall of the chronic fatigue syndrome as defined by Holmes et al.

Abstract:

This paper is a sequel to my monograph on neurocirculatory asthenia and chronic fatigue syndrome. It pays special attention to the nature of chronic fatigue syndrome, to the forms of neurocirculatory asthenia, and above all to the 6th form in which profound fatigue is the dominant symptom. All forms including the 6th are characterized by the presence of concomitant symptoms due to dysfunction of the autonomic nervous system. Chronic fatigue syndrome as defined by Holmes et al is devoid of these symptoms. Up till the present day no case histories of it have been published. It is argued that chronic fatigue syndrome sensu Holmes et al does not exist, the 6th form of neurocirculatory asthenia having to take up its place.

 

Source: van Waveren EK. The rise and fall of the chronic fatigue syndrome as defined by Holmes et al. Med Hypotheses. 1996 Feb;46(2):63-6. http://www.ncbi.nlm.nih.gov/pubmed/8692045

 

Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) often complain of an inability to maintain activity levels and a variety of autonomic-like symptoms that make everyday activity intolerable at times. The purpose of the study was to determine if there were differences in vagal activity at fixed breathing rates in women with CFS.

Twelve women with the diagnosis of CFS between the ages of 32 and 59 years volunteered for the study. Healthy women, who were between the ages of 30 and 49, served as controls. Full signal electrocardiograph and respiratory signals were collected during a paced breathing protocol of three fixed breathing rates (8, 12 and 18 breaths/min) performed in the sitting and standing postures. Vagal activity was analyzed by means of heart rate spectral analysis to determine the subject’s response to specific breathing rates and postures. Heart rate variability was used as a non-invasive method of measuring the parasympathetic component of the autonomic nervous system.

Using this method, although there was significantly less vagal power in the sitting versus the standing postures for both groups, the overall vagal power was significantly lower (p < 0.034) in the CFS group versus healthy controls. Vagal power was also significantly lower (p < 0.01 to p < 0.05) at all breathing rates in both postures except while standing and breathing at 18 breaths/min. Knowledge of the differences in vagal activity for CFS patients may allow stratification for the analysis of other research variables.

 

Source: Sisto SA, Tapp W, Drastal S, Bergen M, DeMasi I, Cordero D, Natelson B. Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome. Clin Auton Res. 1995 Jun;5(3):139-43. http://www.ncbi.nlm.nih.gov/pubmed/7549414

 

Sympathetic overactivity in subjects complaining of unexplained fatigue

Abstract:

Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate.

Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively.

We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest.

The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.

 

Source: Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A. Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci (Lond). 1994 Dec;87(6):655-61. http://www.ncbi.nlm.nih.gov/pubmed/7874856