Tag: noradrenaline

Central noradrenergic deficiency in post-infectious chronic fatigue: Neurobehavioral correlates

Abstract:

Fatigue, brain fog and post-exertional malaise are major features of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2. To date, no specific neurotransmitter abnormalities have been found in either condition. We examined the possibility of central catecholaminergic involvement and clinical correlates in post-infectious myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 groups compared to healthy volunteers and, as positive controls, Parkinson’s disease patients.

In an observational, cross-sectional cohort study conducted at the National Institutes of Health Clinical Center we measured CSF levels of catecholamines and metabolites in the four groups and assessed correlations with neurobehavioral measures. CSF indices of the central Norepinephrine Pathway (norepinephrine + 3,4-dihydroxyphenylglycol + 3-methoxy-4-hydroxyphenylglycol) and Dopamine Pathway (dopamine + 3,4-dihydroxyphenylacetic acid + homovanillic acid) were measured and related to patient-recorded outcomes and physiological assessments.

Mean values for Norepinephrine Pathway activity (in pmol/mL) were lower in the post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, post-acute sequelae of severe acute respiratory syndrome coronavirus 2, and Parkinson’s disease groups compared to the healthy volunteer cohort (post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (-15.9, 95% confidence interval [-26.1, -5.7], P = 0.0006); post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (-9.62, [-17.9, -1.4], P = 0.015); Parkinson’s disease (-19.4, [-27.5, -11.3], P < 0.0001)).

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 participants with post-exertional malaise had evidence of central noradrenergic deficiency compared to healthy volunteers (-18.3 [-31.3, -5.3], P = 0.0018). The post-infectious myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 groups did not differ from the healthy group in values for the Dopamine Pathway index. Across all participants, Norepinephrine Pathway activity correlated positively with handgrip duration and general health and negatively with fatigue.

We conclude that post-infectious myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 feature a specific central neurotransmitter pattern involving noradrenergic but not dopaminergic deficiency. The noradrenergic abnormality is associated with major symptoms such as post-exertional malaise.

Source: Aregawi L, Walitt B, Sullivan P, Norato G, Benjamin RN, Goldstein DS. Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates. Brain Commun. 2026 May 13;8(3):fcag173. doi: 10.1093/braincomms/fcag173. PMID: 42205163; PMCID: PMC13202209. https://pmc.ncbi.nlm.nih.gov/articles/PMC13202209/ (Full text)

Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue lasting 6 months or longer. CFS has been associated with a disturbed (re-)activity of the autonomic nervous system. However, the sympathetic adrenomedulla (SAM) remains under-examined in CFS.

To investigate SAM reactivity, we implemented a submaximal cycle ergometry (ERGO) and a pharmacological test (Insulin Tolerance Test, ITT) in 21 CFS patients and 20 age-, sex-, and BMI-matched controls. Plasma norepinephrine and epinephrine were collected once before and twice after the tests (+10/+20, and +30 min).

Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls, while the groups did not differ in their responses to the ITT.

To conclude, we found evidence of altered sympathetic-neural and SAM reactivity in CFS. Exercise stress revealed a subtle catecholaminergic hyporeactivity in CFS patients. It is conceivable that inadequate catecholaminergic responses to physical exertion might contribute to CFS symptoms.

Copyright © 2013 Elsevier B.V. All rights reserved.

 

Source: Strahler J, Fischer S, Nater UM, Ehlert U, Gaab J. Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome. Biol Psychol. 2013 Sep;94(1):160-6. doi: 10.1016/j.biopsycho.2013.06.002. Epub 2013 Jun 13. https://www.ncbi.nlm.nih.gov/pubmed/23770415

 

Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report

Abstract:

BACKGROUND: Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS.

CASE PRESENTATION: A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1β and IL-6 (pyretic cytokines), tumor necrosis factor-α and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview.

CONCLUSIONS: A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients.

 

Source: Oka T, Kanemitsu Y, Sudo N, Hayashi H, Oka K. Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report. Biopsychosoc Med. 2013 Mar 8;7(1):7. doi: 10.1186/1751-0759-7-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599992/ (Full article)

 

Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal

Abstract:

RATIONALE: Subjective and objective impairments in neuropsychological function have been reported in chronic fatigue syndrome (CFS) patients under conditions of high arousal. These impairments may reflect impaired central noradrenaline function such as impaired post-synaptic alpha-2 adrenoceptor function.

OBJECTIVES: To determine whether high-dose clonidine has greater agonist effects at central post-synaptic alpha-2 receptors in CFS patients than controls under conditions of high arousal. As a result clonidine may reverse neuropsychological deficits underlying symptoms of poor concentration and memory.

METHODS: High-dose clonidine (2.5 mg/kg) and placebo challenge tests were given in random order to ten medication-free CFS patients without anxiety disorders, depressive disorders or migraine and ten matched healthy controls under the same stressors (timed neuropsychological testing, venous sampling, intravenous drug administration). Growth hormone, cortisol, blood pressure, pulse rate, visual analogue scales of subjective neuropsychological performance and the performance on several tests from a computerised neuropsychological battery were measured.

RESULTS: In CFS patients versus controls, clonidine enhanced both growth hormone ( P = 0.028) and cortisol release ( P = 0.021) and increased speed in the initial stage of a planning task ( P = 0.023). There were no other differences between CFS patients and controls on hormonal, physiological, symptomatic or neuropsychological measures.

CONCLUSIONS: Under conditions of high arousal, CFS patients may display supersensitive central post-synaptic alpha-2 adrenoceptor function associated with the release of cortisol and growth hormone and initial thinking time in planning tasks.

 

Source: Morriss RK, Robson MJ, Deakin JF. Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal. Psychopharmacology (Berl). 2002 Sep;163(2):166-73. Epub 2002 Jul 30. http://www.ncbi.nlm.nih.gov/pubmed/12202963