Tag: Demitrack

Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) fall into the spectrum of what might be termed stress-associated syndromes by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. These illnesses also share perturbation of the hypothalamic-pituitary-adrenal axis and sympathetic stress response systems. In this article, the authors discuss the specific neurohormonal abnormalities found in FM and CFS and potential mechanisms by which dysfunction of neurohormonal stress-response systems could contribute to vulnerability to stress-associated syndromes and to the symptoms of FM and CFS.

 

Source: Crofford LJ, Demitrack MA. Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 1996 May;22(2):267-84. http://www.ncbi.nlm.nih.gov/pubmed/8860799

 

Seasonal symptom variation in patients with chronic fatigue: comparison with major mood disorders

Abstract:

The psychobiology of idiopathic fatigue has received renewed interest in the medical literature in recent years. In order to examine the relation between chronic, idiopathic fatigue and specific subtypes of depressive illness, we characterized the pattern and severity of seasonal symptom variation in 73 patients with chronic, idiopathic fatigue, compared to patients with major depression (n = 55), atypical depression (n = 35), and seasonal affective disorder (n = 16) Fifty of the fatigued subjects also met the specific Centers for Disease Control and Prevention case criteria for chronic fatigue syndrome, though this definition was unable to discriminate a distinct subgroup of patients, based on their seasonality scores alone. As a group, the fatigued subjects reported the lowest levels of symptom seasonality of any of the study groups. Further, even in those fatigued subjects with scores in the range of those seen in patients with seasonal affective disorder, seasonality was not reported to be a subjectively distressing problem. These findings lend support to the idea that although chronic fatigue shares some clinical features with certain mood disorders, they are not the same illnesses. These data are also consistent with the emerging view that chronic fatigue represents a heterogeneously determined clinical condition.

 

Source: Zubieta JK, Engleberg NC, Yargiç LI, Pande AC, Demitrack MA. Seasonal symptom variation in patients with chronic fatigue: comparison with major mood disorders. J Psychiatr Res. 1994 Jan-Feb;28(1):13-22. http://www.ncbi.nlm.nih.gov/pubmed/8064638

 

Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings

Abstract:

The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature.

The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness “chronic fatigue syndrome.” Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis.

In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals.

Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity.

 

Source: Demitrack MA, Gold PW, Dale JK, Krahn DD, Kling MA, Straus SE. Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings. Biol Psychiatry. 1992 Dec 15;32(12):1065-77. http://www.ncbi.nlm.nih.gov/pubmed/1282370

 

Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is characterized by persistent or relapsing debilitating fatigue for at least 6 months in the absence of a medical diagnosis that would explain the clinical presentation. Because primary glucocorticoid deficiency states and affective disorders putatively associated with a deficiency of the arousal-producing neuropeptide CRH can be associated with similar symptoms, we report here a study of the functional integrity of the various components of the hypothalamic-pituitary-adrenal axis in patients meeting research case criteria for chronic fatigue syndrome.

Thirty patients and 72 normal volunteers were studied. Basal activity of the hypothalamic-pituitary-adrenal axis was estimated by determinations of 24-h urinary free cortisol-excretion, evening basal plasma total and free cortisol concentrations, and the cortisol binding globulin-binding capacity. The adrenal cortex was evaluated indirectly by cortisol responses during ovine CRH (oCRH) stimulation testing and directly by cortisol responses to graded submaximal doses of ACTH. Plasma ACTH and cortisol responses to oCRH were employed as a direct measure of the functional integrity of the pituitary corticotroph cell. Central CRH secretion was assessed by measuring its level in cerebrospinal fluid.

Compared to normal subjects, patients demonstrated significantly reduced basal evening glucocorticoid levels (89.0 +/- 8.7 vs. 148.4 +/- 20.3 nmol/L; P less than 0.01) and low 24-h urinary free cortisol excretion (122.7 +/- 8.9 vs. 203.1 +/- 10.7 nmol/24 h; P less than 0.0002), but elevated basal evening ACTH concentrations.

There was increased adrenocortical sensitivity to ACTH, but a reduced maximal response [F(3.26, 65.16) = 5.50; P = 0.0015). Patients showed attenuated net integrated ACTH responses to oCRH (128.0 +/- 26.4 vs. 225.4 +/- 34.5 pmol/L.min, P less than 0.04). Cerebrospinal fluid CRH levels in patients were no different from control values (8.4 +/- 0.6 vs. 7.7 +/- 0.5 pmol/L; P = NS).

Although we cannot definitively account for the etiology of the mild glucocorticoid deficiency seen in chronic fatigue syndrome patients, the enhanced adrenocortical sensitivity to exogenous ACTH and blunted ACTH responses to oCRH are incompatible with a primary adrenal insufficiency. A pituitary source is also unlikely, since basal evening plasma ACTH concentrations were elevated.

Hence, the data are most compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH or some other central stimulus to the pituitary-adrenal axis. Whether a mild glucocorticoid deficiency or a putative deficiency of an arousal-producing neuropeptide such as CRH is related to the clinical symptomatology of the chronic fatigue syndrome remains to be determined.

 

Source: Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos GP, Gold PW. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. 1991 Dec;73(6):1224-34. http://www.ncbi.nlm.nih.gov/pubmed/1659582