Tag: neuroendocrinology

Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescent. The disease mechanisms are unknown. Previous studies have suggested elevated plasma levels of several cytokines, but a recent meta-analysis of 38 articles found that of 77 different cytokines measured in plasma, transforming growth factor beta (TGF-β) was the only one that was elevated in patients compared to controls in a sufficient number of articles. In the present study we therefore compared the plasma levels of the three TGF-β isoforms in adolescent CFS patients and healthy controls. In addition, the study explored associations between TGF-β levels, neuroendocrine markers, clinical markers and differentially expressed genes within the CFS group.

METHODS: CFS patients aged 12-18 years (n = 120) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls (n = 68) were recruited from local schools. The three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) were assayed using multiplex technology. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. Whole blood gene expression was assessed by RNA sequencing in a subgroup of patients (n = 29) and controls (n = 18).

RESULTS: Plasma levels of all three isoforms of TGF-β were equal in the CFS patients and the healthy controls. Subgrouping according to the Fukuda and Canada 2003 criteria of CFS did not reveal differential results. Within the CFS group, all isoforms of TGF-β were associated with plasma cortisol, urine norepinephrine and urine epinephrine, and this association pattern was related to fatigue score. Also, TGF-β3 was related to expression of the B cell annotated genes TNFRSF13C and CXCR5.

CONCLUSIONS: Plasma levels of all TGF-β isoforms were not altered in adolescent CFS. However, the TGF-β isoforms were associated with neuroendocrine markers, an association related to fatigue score. Furthermore, TGF-β3 might partly mediate an association between plasma cortisol and B cell gene expression. Trial registration Clinical Trials NCT01040429.

Source: Wyller VB, Nguyen CB, Ludviksen JA, Mollnes TE. Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome. J Transl Med. 2017 Dec 4;15(1):245. doi: 10.1186/s12967-017-1350-1. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1350-1 (Full article)

Neuroendocrine aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the neuroendocrine system. A symposium was organized in March 2001 to explore the possibility of an association between neuroendocrine dysfunction and CFS, with special emphasis on the interactions between neuroendocrine dysfunction and other abnormalities noted in the immune and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Copyright 2004 S. Karger AG, Basel

 

Source: Papanicolaou DA1, Amsterdam JD, Levine S, McCann SM, Moore RC, Newbrand CH, Allen G, Nisenbaum R, Pfaff DW, Tsokos GC, Vgontzas AN, Kales A. Neuroendocrine aspects of chronic fatigue syndrome. Neuroimmunomodulation. 2004;11(2):65-74. http://www.ncbi.nlm.nih.gov/pubmed/14758052

 

The neuroendocrinology of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a common and disabling problem; although most likely of biopsychosocial origin, the nature of the pathophysiological components remains unclear. There has been a wealth of interest in the endocrinology of this condition, which will be reviewed in this article. Most studied has been the hypothalamic-pituitary-adrenal (HPA) axis; although the quality of many studies is poor, the overall balance of evidence points to reduced cortisol output in at least some patients, with some evidence that this is linked to symptom production or persistence.

There is evidence for heightened negative feedback and glucocorticoid receptor function and for impaired ACTH and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication, and ongoing stress, it seems likely that HPA axis disturbance is heterogeneous and of multifactorial etiology in CFS. Studies assessing GH, dehydroepiandrostenedione and its sulfate, melatonin, leptin, and neuroendocrine-monoamine interactions are also reviewed.

There is some evidence from these studies to suggest alterations of dehydroepiandrostenedione sulfate function and abnormal serotonin function in CFS, but whether these changes are of functional importance remains unclear. To obtain a clearer assessment of the etiological and pathophysiological relevance of endocrine changes in CFS, it is suggested that more prospective cohort studies be undertaken in groups at high risk for CFS, that patients with CFS are followed up into recovery, and that multidimensional assessments are undertaken to unravel the influence of the various confounding factors on the observed endocrine changes in CFS.

 

Source: Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr Rev. 2003 Apr;24(2):236-52. http://www.ncbi.nlm.nih.gov/pubmed/12700181

 

The neuroendocrinology of chronic fatigue syndrome and fibromyalgia

Abstract:

BACKGROUND: Disturbance of the HPA axis may be important in the pathophysiology of chronic fatigue syndrome (CFS) and fibromyalgia. Symptoms may be due to: (1) low circulating cortisol; (2) disturbance of central neurotransmitters; or (3) disturbance of the relationship between cortisol and central neurotransmitter function. Accumulating evidence of the complex relationship between cortisol and 5-HT function, make some form of hypothesis (3) most likely. We review the methodology and results of studies of the HPA and other neuroendocrine axes in CFS.

METHOD: Medline, Embase and Psychlit were searched using the Cochrane Collaboration strategy. A search was also performed on the King’s College CFS database, which includes over 3000 relevant references, and a citation analysis was run on the key paper (Demitrack et al. 1991).

RESULTS: One-third of the studies reporting baseline cortisol found it to be significantly low, usually in one-third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function, and enhanced 5-HT function on neuroendocrine challenge tests. The opioid system, and arginine vasopressin (AVP) may also be abnormal, though the growth hormone (GH) axis appears to be intact, in CFS.

CONCLUSIONS: The significance of these changes, remains unclear. We have little understanding of how neuroendocrine changes relate to the experience of symptoms, and it is unclear whether these changes are primary, or secondary to behavioural changes in sleep or exercise. Longitudinal studies of populations at risk for CFS will help to resolve these issues.

 

Source: Parker AJ, Wessely S, Cleare AJ. The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychol Med. 2001 Nov;31(8):1331-45. http://www.ncbi.nlm.nih.gov/pubmed/11722149

 

Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of interest to examine if these two syndromes have pathogenetic as well as clinical features in common. Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy controls. An attractive hypothesis relating sleep disturbance, altered somatotropic neuroendocrine function and fibromyalgia symptoms has been put forward as a plausible pathogenic mechanism for fibromyalgia syndrome. We therefore sought to investigate the level of somatomedin C in patients with chronic fatigue syndrome.

Somatomedin C levels were determined by radioimmunoassay in frozen serum specimens from 49 patients with CFS and 30 healthy blood donor control subjects of similar age and gender. Somatomedin C levels were higher in patients with CFS than in healthy control subjects (255.3 +/- 68.5 vs 211.9 +/- 76.2, P = 0.01). There was no effect of gender, use of nonsteroidal anti-inflammatory drugs or tricyclic drugs on levels of somatomedin C. There was a tendency for somatomedin C levels to fall with age.

In contrast to patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic neuroendocrine axis.

 

Source: Bennett AL, Mayes DM, Fagioli LR, Guerriero R, Komaroff AL. Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):91-6. http://www.ncbi.nlm.nih.gov/pubmed/9201651

 

Neuroendocrine correlates of chronic fatigue syndrome: a brief review

Abstract:

Chronic fatigue syndrome remains one of the more perplexing syndromes in contemporary clinical medicine. One approach to understanding this condition has been to acknowledge its similarities to other disorders of clearer pathophysiology.

In this review, a rationale for the study of neuroendocrine correlates of chronic fatigue syndrome is presented, based in part on the clinical observation that asthenic or fatigue states share many of the somatic symptom characteristics seen in recognized endocrine disorders. Of additional interest is the observation that psychological symptoms, particularly disturbances in mood and anxiety, are equally prominent in this condition.

At this time, several reports have provided replicated evidence of disruptions in the integrity of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. It is notable that the pattern of the alteration in the stress response apparatus is not reminiscent of the well-understood hypercortisolism of melancholic depression but, rather, suggests a sustained inactivation of central nervous system components of this system.

Recent work also implicates alterations in central serotonergic tone in the overall pathophysiology of this finding. The implications of these observations are far from clear, but they highlight the fact that, though chronic fatigue syndrome overlaps with the well-described illness category of major depression, these are not identical clinical conditions.

 

Source: Demitrack MA. Neuroendocrine correlates of chronic fatigue syndrome: a brief review. J Psychiatr Res. 1997 Jan-Feb;31(1):69-82. http://www.ncbi.nlm.nih.gov/pubmed/9201649

 

Short-term night-shift working mimics the pituitary-adrenocortical dysfunction in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether a short period (5 days) of night-shift work affected the pituitary-adrenal responses to CRH. Ten nurses (8 female and 2 male; age 28.1 +/- 1.7 yr: mean +/- SEM) working at the Royal Liverpool University Hospital, and who regularly undertook periods of night and day shift work were enrolled.

Measurements were made of basal ACTH and cortisol concentrations, and their responses to iv ovine CRH (1 microgram.kg-1). Basal ACTH concentrations were higher during the night shift than during the day shift (12.9 +/- 5.1 pmol.L-1 vs. 4.7 +/- 1.2 pmol.L-1, P < 0.01) whereas cortisol concentrations were lower (551 +/- 48 nmol.L – 1 vs. 871 +/- 132 nmol.L – 1, P < 0.01). After CRH injection, ACTH concentrations remained consistently higher during the night shift, but the integrated increase in ACTH concentration was lower (P < 0.05) than during the day shift. Conversely, the increase in cortisol concentration was greater during the night shift than the day shift (283 +/- 53 nmol.L-1 vs. 134 +/- 41 nmol.L-1, P < 0.05).

We conclude that the pituitary-adrenal responses to CRH are markedly disrupted after only 5 days of nighttime work. These abnormalities mimic those previously observed in patients with chronic fatigue syndrome. Neuroendocrine abnormalities reported to be characteristic of chronic fatigue syndrome may be merely the consequence of disrupted sleep and social routine.

 

Source: Leese G, Chattington P, Fraser W, Vora J, Edwards R, Williams G. Short-term night-shift working mimics the pituitary-adrenocortical dysfunction in chronic fatigue syndrome. J Clin Endocrinol Metab. 1996 May;81(5):1867-70. http://www.ncbi.nlm.nih.gov/pubmed/8626849

 

Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome

Abstract:

The justification for disordered chronobiology for fibromyalgia and chronic fatigue syndrome (CFS) is based on the following evidence: The studies on disordered sleep physiology and the symptoms of fibromyalgia and CFS; the experimental studies that draw a link between interleukin-1 (IL-1), immune-neuroendocrine-thermal systems and the sleep-wake cycle; studies and preliminary data of the inter-relationships of sleep-wakefulness, IL-1, and aspects of peripheral immune and neuroendocrine functions in healthy men and in women during differing phases of the menstrual cycle; and the observations of alterations in the immune-neuroendocrine functions of patients with fibromyalgia and CFS (Moldofsky, 1993b, d). Time series analyses of measures of the circadian pattern of the sleep-wake behavioural system, immune, neuroendocrine and temperature functions in patients with fibromyalgia and CFS should determine whether alterations of aspects of the neuro-immune-endocrine systems that accompany disordered sleep physiology result in nonrestorative sleep, pain, fatigue, cognitive and mood symptoms in patients with fibromyalgia and CFS.

 

Source: Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. Adv Neuroimmunol. 1995;5(1):39-56. http://www.ncbi.nlm.nih.gov/pubmed/7795892

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

Abstract:

Operational diagnostic criteria for fibromyalgia were applied to most clinical studies during the past year. Similar diagnostic criteria for chronic fatigue syndrome are being revised, but criteria for myofascial pain have not been agreed on or tested. Intense research efforts focused on the role of neurohormones and the hypothalamic-pituitary-adrenal axis in fibromyalgia and chronic fatigue syndrome over the past year.

 

Source: Goldenberg DL. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol. 1993 Mar;5(2):199-208. http://www.ncbi.nlm.nih.gov/pubmed/8452771

 

The neuropsychiatry of chronic fatigue syndrome

Abstract:

This paper explores the relationship between chronic fatigue syndrome (CFS) and psychiatric disorder, with special reference to neuropsychiatry, Topics reviewed include (1) epidemiological evidence of central disorder in CFS; (2) evidence from longitudinal studies of an interaction between vulnerability to CFS and psychiatric disorder; and (3) evidence from neuroimaging, neuropsychology, neurophysiology and neuroendocrinology of disordered CNS function in CFS. The most impressive evidence of CNS disturbance comes from neuroendocrinological studies, which suggest a role of hypothalamic disorder as a final common pathway for CFS. It is concluded that the equal and opposite tendencies of psychiatry to be ‘brainless’ and neurology to be ‘mindless’ have led to needless controversy over the nature of CFS. Now that the contributions of psychiatric disorder to CFS, and of neurobiological dysfunction to psychiatric disorder, are both established, it will be possible to make real advances in understanding the nature of CFS.

 

Source: Wessely S. The neuropsychiatry of chronic fatigue syndrome. Ciba Found Symp. 1993;173:212-29; discussion 229-37. http://www.ncbi.nlm.nih.gov/pubmed/8491099