Tag: serotonin

Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has been associated with increased prolactin (PRL) responses to the serotonin (5-HT) releasing agent fenfluramine. It is not known whether this abnormality is due to increased 5-HT release or heightened sensitivity of post-synaptic 5-HT receptors.

METHODS: We measured the increase in plasma PRL produced by the directly acting 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP), in patients with CFS and healthy controls. We also compared the ability of mCPP to lower slow wave sleep (SWS) in the sleep polysomnogram of both subject groups. Finally, we measured plasma amino-acid levels to determine whether tryptophan availability differed between CFS subjects and controls.

RESULTS: mCPP elevated plasma PRL equivalently in patients with CFS and controls. Similarly, the decrease in SWS produced by mCPP did not differ between the two subject groups. Plasma-free tryptophan was significantly decreased in CFS.

CONCLUSIONS: The sensitivity of post-synaptic 5-HT2c receptors is not increased in patients with CFS. This suggests that the increased PRL response to fenfluramine in CFS is due to elevated activity of pre-synaptic 5-HT neurones. This change is unlikely to be due to increased peripheral availability of tryptophan.

 

Source: Vassallo CM, Feldman E, Peto T, Castell L, Sharpley AL, Cowen PJ. Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome. Psychol Med. 2001 May;31(4):585-91. http://www.ncbi.nlm.nih.gov/pubmed/11352361

 

Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists–preliminary results

Abstract:

OBJECTIVE: The serotonin system presumably is involved in the pathogenesis of chronic fatigue syndrome (CFS). Results from a few studies led to the hypothesis of a “postsynaptic hyperresponsiveness” in CFS. Therefore we intended to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

PATIENTS AND METHODS: 2 patient groups (10 patients each; CFS according to the CDC classification criteria) received either oral tropisetron (5 mg once daily) or oral ondansetron (2 x 8 mg daily), open-labelled. Treatment duration was 15 days. Treatment response was evaluated by visual analog scales (VAS) for fatigue and capability.

RESULTS: 19 patients finished their respective study. In the tropisetron group 6/9 (VAS fatigue) and 7/9 (VAS capability) patients documented benefit, 8/10 rsp. 8/10 patients in the ondansetron group. The score changes (VAS before and after treatment) in case of response were more pronounced in the tropisetron group. The frequency of concomitant symptoms did not differ significantly in the treatment groups. The overall analysis of both studies showed a remarkable improvement (> or = 35%) of approximately one third of the patients in both VAS. Treatment was well tolerated.

CONCLUSION: Our preliminary results encourage to perform placebo-controlled, double-blind studies to further evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Source: Späth M, Welzel D, Färber L. Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists–preliminary results. Scand J Rheumatol Suppl. 2000;113:72-7. http://www.ncbi.nlm.nih.gov/pubmed/11028837

The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity

Abstract:

The authors compared in a group of 118 patients with autoimmune thyroiditis and a positive antibody titre against ovaries the grade of fatigue with the presence of organ specific and non-specific autoantibodies in the peripheral blood stream, antibodies against EBV and CMV, immunoglobulin concentrations, biochemical parameters of the lipid metabolism, glucose tolerance, ion balance and melatonin and serotonin levels. Patients with autoimmune thyroiditis were differentiated according to the degree of fatigue into three groups: 38 with fatigue typical for CFS, 30 with occasional fatigue and 50 without the feeling of fatigue.

Fatigue of the CFS type was characterized by a significantly higher incidence of autoantibodies against the adrenals and a higher cholesterol level. Increased fatigue of the patients was associated with a lower melatonin level, a higher serotonin level and a lower M/S ratio as compared with patients without fatigue. In other indicators no differences were found. Fatigue in CFS could be associated, similarly as in autoimmune endocrinopathies, with impaired immunoendocrine regulation. In autoimmune thyroiditis, regardless of the concomitant presence of fatigue, in addition to antibodies against thyroid peroxidase most frequently antibodies against the ovaries were detected.

 

Source: Sterzl I, Fucíková T, Hrdá P, Matucha P, Zamrazil V. The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity. Vnitr Lek. 1998 Aug;44(8):456-60. [Article in Czech] http://www.ncbi.nlm.nih.gov/pubmed/10358448

 

Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms.

Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia).

How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function.

In order to provide a more refined view of the nature of the HPA disturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition.

 

Source: Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann N Y Acad Sci. 1998 May 1;840:684-97. http://www.ncbi.nlm.nih.gov/pubmed/9629295

 

Increased brain serotonin function in men with chronic fatigue syndrome

Recent neuroendocrine studies suggest that patients with chronic fatigue syndrome may have increased brain serotonin activity.1 2 This could be relevant to the pathophysiology of chronic fatigue syndrome because serotonin pathways have a role in mediating central fatigue.3 Currently, however, the existence of abnormal serotonin neuroendocrine function in patients with chronic fatigue syndrome is controversial because of contradictory findings from samples of heterogeneous patients 4 5 and the use of serotonin probes such as buspirone, which are of doubtful pharmacological specificity.1 We aimed to measure the increase in plasma prolactin after administration of the selective serotonin releasing agent d-fenfluramine in men rigorously diagnosed as having the chronic fatigue syndrome and carefully matched healthy controls.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127129/pdf/9251547.pdf

 

Source: Sharpe M, Hawton K, Clements A, Cowen PJ. Increased brain serotonin function in men with chronic fatigue syndrome. BMJ. 1997 Jul 19;315(7101):164-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127129/

 

Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome

Abstract:

We examined 5HT1a-mediated ACTH release in patients with chronic fatigue syndrome (CFS) using a between-subjects design. Patients attending a specialist outpatient clinic for CFS, who fulfilled CDC criteria, together with age- and sex-matched healthy comparison subjects, were recruited. Subjects had a cannula inserted in a forearm vein at 0830 h and were allowed to relax until 0900 h, when baseline bloods for ACTH and cortisol were drawn.

They were then given ipsapirone 20 mg PO and further blood for hormone estimation was taken at +30, +60, +90, +120 and +180 min. Baseline ACTH and cortisol levels did not differ between the two groups. Release of ACTH (but not cortisol) in response to ipsapirone challenge was significantly blunted in patients with CFS. We conclude that serotonergic activation of the hypothalamic-pituitary-adrenal axis is defective in CFS. This defect may be of pathophysiological significance.

 

Source: Dinan TG, Majeed T, Lavelle E, Scott LV, Berti C, Behan P. Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychoneuroendocrinology. 1997 May;22(4):261-7. http://www.ncbi.nlm.nih.gov/pubmed/9226729

 

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

 

Increased prolactin response to buspirone in chronic fatigue syndrome

Abstract:

We studied the endocrine and subjective responses that followed acute administration of the 5-HT1A receptor agonist buspirone (0.5 mg/kg orally) in 11 male patients with chronic fatigue syndrome (CFS) and a group of matched healthy controls.

Patients with CFS had significantly higher plasma prolactin concentrations and experienced more nausea in response to buspirone than did controls. However, the growth hormone response to buspirone did not distinguish CFS patients from controls.

Our data question whether the enhancement of buspirone-induced prolactin release in CFS is a consequence of increased sensitivity of post-synaptic 5-HT1A receptors. It is possible that the increased prolactin response to buspirone in CFS could reflect changes in dopamine function.

 

Source: Sharpe M, Clements A, Hawton K, Young AH, Sargent P, Cowen PJ. Increased prolactin response to buspirone in chronic fatigue syndrome. J Affect Disord. 1996 Nov 4;41(1):71-6. http://www.ncbi.nlm.nih.gov/pubmed/8938208

 

Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome

Abstract:

Prolactin and cortisol responses to dl-fenfluramine challenge were examined in 11 patients with chronic fatigue syndrome and in 11 healthy controls who were age and gender matched. After obtaining two baseline samples, each subject was given 60 mg of dl-fenfluramine orally and further blood samples were drawn hourly during the following five hours in order to measure prolactin and cortisol levels. There was no difference in either baseline or fenfluramine-induced hormonal responses between patients with chronic fatigue syndrome and controls. There was also no correlation between depression scores on HAM-D and hormonal responses in patients with chronic fatigue syndrome. The findings of this study do not support a role for 5-HT in chronic fatigue syndrome.

Comment in: Re: Endocrine responses to fenfluramine challenge in chronic fatigue syndrome. [Can J Psychiatry. 1996]

 

Source: Yatham LN, Morehouse RL, Chisholm BT, Haase DA, MacDonald DD, Marrie TJ. Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome. Can J Psychiatry. 1995 Mar;40(2):93-6. http://www.ncbi.nlm.nih.gov/pubmed/7788624

 

Pharmacological approaches to the therapy of chronic fatigue syndrome

Abstract:

Although a variety of pharmacological agents have been used to treat patients with chronic fatigue syndrome none has been shown to effect a complete resolution of symptoms.

Data obtained from a retrospective study and from an objective assessment of the aerobic work capacity of patients with this disorder suggest that the underlying pathophysiological abnormality is a disorder of sleep regulation. This results not only in profound fatigue and lethargy but also reduced sensory threshold for pain, disordered temperature regulation, cardiovascular abnormalities, disturbed higher cerebral function and mental depression.

Drugs which modulate sleep, such as tricyclic antidepressants, have a limited effect in improving the symptoms that CFS patients experience. We suggest that other agents which affect central nervous system neurotransmitters, particularly serotonin, may have potential in the management of this condition and need to be evaluated in large controlled clinical trials.

 

Source: McCluskey DR. Pharmacological approaches to the therapy of chronic fatigue syndrome. Ciba Found Symp. 1993;173:280-7; discussion 287-97. http://www.ncbi.nlm.nih.gov/pubmed/8491103