Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295330
Title: Neuroendocrine alterations in chronic fatigue syndrome
Author: Majeed, Tahir
ISNI:       0000 0001 3617 0296
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1996
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Abstract:
Chronic fatigue syndrome (CFS) is an illness that occurs worldwide. Over the years the syndrome has had various labels, ranging from the Victorian one of neurasthenia to the putative neurological diagnosis of benign myalgic encephalomyelitis (Acheson 1959). A working case definition was published by the Centers for Disease Control in 1988 (Holmes et al) and revised in 1994 (Fukuda et al). In the initial studies of patients with CFS, impaired activation of hypothalamic-pituitary-adrenal (HPA) axis (Demitrack et al 1991) and monoaminergic dysfunction (Demitrack et al 1992; Bakheit et al 1992) was reported. Dynamic neuroendocrine challenge tests provide one of the only methods for examining neurotransmitter function in vivo in humans (Checkley 1980). In the following studies these tests were used to examine different neurotransmitter systems and their influence on the functional activity of the HP A, hypothalamic-somatotroph and hypothalamic-prolactin axes. In the first study, serotonin (5-HT) function in CFS was evaluated using the specific 5-HT1A receptor agonist, buspirone. It was found that prolactin responses to this agent were augmented in patients with chronic fatigue syndrome compared to healthy controls. This finding does not support the view that CFS is a form of depressive disorder because in depression, prolactin responses to this 5-HT1A agonist (Bakheit et al 1992) and to d-fenfluramine (Cleare et al 1995) are blunted reflecting decreased 5-HT neurotransmission. The study is therefore of importance in suggesting that CFS unlike depression, may be associated with increased 5-HT function. The second study is based on the hypothesis that abnormalities in the HPA-axis (Demitrack et al 1991) arise from a disturbance in serotinergic neurotransmission. ACTH and cortisol responses to the selective 5-HT1A receptor agonist ipsapirone were examined; no differences in baseline ACTH and cortisol levels were found but in CFS, there was significant attenuation of ACTH release. Study 3 was designed to demonstrate the functional integrity of the hypothalamic-somatotroph axis and its interaction with the HPA-axis. Growth hormone (GH) responses to dexamethasone were examined in two phases, before and after the administration of metyrapone, an inhibitor of 11-beta hydroxylation, given to block steroid synthesis and upregulate brain steroid receptors. Blunted responses were recorded in each phase in patients with CFS and depression compared to healthy controls. It is concluded that the abnormality found is compatible with a decrease response and/or a lack of plasticity in cerebral glucocorticoid receptors. In study 4, noradrenergic function was examined by measuring GH responses to the monoamine reuptake inhibitor, desipramine; blunted responses were found in patients with CFS, compared to healthy individuals. It is concluded that the attenuated response is due to decreased sensitivity of the alpha2-postsynaptic adrenoceptor, secondary to a hyperadrenergic state, indicating that central noradrenergic function is decreased in patients with CFS. In study 5, growth hormone responses to anticholinesterase, pyridostigmine were examined: augmented responses were found in the CFS group, compared to the healthy individuals. This enhanced response reflects increased sensitivity of acetylcholine (ACh) neurotransmitter function in CFS. In studies 6 & 7, growth hormone responses to the dopamine agonist, bromocriptine, and to the GABA(B) agonist, baclofen, were measured in order to assess dopamine (DA) and GABA neurotransmitter function. The responses in patients with CFS were the same as in the healthy controls. It is concluded that dopamine (DA) and GABA neurotransmitter systems are not involved in the pathophysiology of CFS. In summary, the neuroendocrine investigations revealed positive findings of a) upregulation of 5-HT receptors with increased 5-HT function, b) impaired activation of the FTPA-axis to serotonin input, c) cerebral steroid receptor resistance and d) reciprocal dysfunction in noradrenaline (NE) and acetylcholine (ACh)-mediated endocrine responses. These findings suggest that CFS is an organic illness with definite neuroendocrine abnormalities. Some of the neuroendocrine abnormalities are similar to those reported in depression, suggesting the reason why these two illnesses may share common symptoms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.295330  DOI: Not available
Keywords: Medicine
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