Tag: neuropeptides

Low Vasopressin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (P4-4.006)

Abstract:

Objective: To shed light on the pathophysiology of water homeostasis in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), classified by WHO as a neurological disease (ICD 10 code G933).

Background: The complex symptomatology of ME/CFS includes signs suggesting abnormal water homeostasis and hypovolemia. Since many patients report polyuria-polydipsia, we conducted an observational series of plasma and urine osmolality as well as plasma levels of vasopressin (VP) in consecutive patients diagnosed with ME/CFS according to the Canadian Consensus Criteria.

Design/Methods: Plasma and urine osmolality (P-Osm and U-Osm, respectively) and plasma VP levels were measured in 111 patients after overnight fasting and 10-hour fluid deprivation. The clinical routine also included brain MRI and blood chemistry.

Results: Following the fluid deprivation P-Osm was above normal (>292 mOsm/kg) in 61 patients (55.0%) and U-Osm below normal (< 750 mOsm/kg) in 74 patients (66.7%). VP-levels were below the level of detection (<1.6 pg/mL) in 91 patients (82.0%). A normal level of VP in relation to their P-Osm was found in 11 patients (9.9 %). The state resembling a central type of diabetes insipidus (cDI) would in the absence of hypophyseal imaging findings and blood chemistry consistent with any other hypophyseal hormonal defect be classified as idiopathic.

Conclusions: Our findings suggest that deficiency of vasopressin secretion is a fundamental measurable part of the disease mechanisms, which may underlie a number of symptoms in ME/CFS, including the common complaint of orthostatic intolerance.

Source: Helena Huhmar, Lauri Soinne, Per Sjögren, Bo Christer Bertilson, Per Hamid Ghatan, Björn Bragée, and Olli Polo. Low Vasopressin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (P4-4.006) Neurology, April 9, 2024 issue 102 (17_supplement_1) https://doi.org/10.1212/WNL.000000000020576 https://www.neurology.org/doi/10.1212/WNL.0000000000205761

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID

Abstract:

Background Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology.

Methods In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination.

Results Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-β and CNTF, among soluble analytes.

Conclusions Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

Plain language summary The impact of the COVID-19 vaccine on vaccine-naïve individuals suffering from Long COVID is uncertain. This study assessed the experience and immune signatures of 16 unvaccinated participants with Long COVID. A total of 10 participants had improved health status after vaccination, and one person reported only worsening health. As expected, vaccination increased immune cells and antibodies against the viral spike protein. Immune signatures may prove to be predictors of health status after vaccination. However, given the small number of participants, these initial findings need further validation.

Source: Connor B Grady, Bornali Bhattacharjee, Julio Silva, Jillian Jaycox, Lik Wee Lee, Valter Silva Monteiro, Mitsuaki Sawano, Daisy Massey, César Caraballo, Jeff R. Gehlhausen, Alexandra Tabachnikova, Tianyang Mao, Carolina Lucas, Mario A. Peña-Hernandez, Lan Xu, Tiffany J. Tzeng, Takehiro Takahashi, Jeph Herrin, Diana Berrent Güthe, Athena Akrami, Gina Assaf, Hannah Davis, Karen Harris, Lisa McCorkell, Wade L Schulz, Daniel Grffin, Hannah Wei, Aaron M Ring, Leying Guan, Charles Dela Cruz, Akiko Iwasaki, Harlan M Krumholz. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID. medRxiv 2024.01.11.24300929; doi: https://doi.org/10.1101/2024.01.11.24300929. https://www.medrxiv.org/content/10.1101/2024.01.11.24300929v1.full-text (Full text)

Exosome-Associated Mitochondrial DNA from Patients with ME/CFS Stimulates Human Cultured Microglia to Release IL-1β

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease that presents with fatigue, sleep disturbances, malaise, and cognitive problems. The pathogenesis of ME/CFS is presently unknown and serum levels of potential biomarkers have been inconsistent. Here we show that mitochondrial DNA (mtDNA) associated with serum exosomes, is increased in ME/CFS patients only after exercise. Moreover, exosomes isolated from patients with ME/CFS stimulate significant release of IL-1β from cultured human microglia. These results provide evidence that activation of microglia by serum-derived exosomes may serve as a potential novel pathogenetic factor and target for treatment of ME/CFS.

Source: Tsilioni I, Natelson B, Theoharides TC. Exosome-Associated Mitochondrial DNA from Patients with ME/CFS Stimulates Human Cultured Microglia to Release IL-1β. Eur J Neurosci. 2022 Sep 24. doi: 10.1111/ejn.15828. Epub ahead of print. PMID: 36153118. https://pubmed.ncbi.nlm.nih.gov/36153118/

Asthenic disorders as a manifestation of chronic fatigue syndrome

Abstract:

The article explains the changes in terminology and diagnostic criteria for asthenic disorders as manifestations of chronic fatigue syndrome CFS (myalgic encephalomyelitis). Chronic fatigue syndrome is defined as neuroimmune endocrine dysfunction with a purely clinical diagnosis. Probably, viral infections can play a leading role in the pathogenesis. Published diagnostic criteria reveal possible correlations between chronic fatigue syndrome and COVID-19 disease. A promising strategy for the therapy and rehabilitation of patients is the use of smart peptides, a representative of which is the drug cortexin.

Source: Putilina MV. Astenicheskie rasstroistva kak proyavlenie sindroma khronicheskoi ustalosti [Asthenic disorders as a manifestation of chronic fatigue syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(8):125-130. Russian. doi: 10.17116/jnevro2021121081125. PMID: 34481448. [Abstract in English, Russian] https://pubmed.ncbi.nlm.nih.gov/34481448/

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a complex, multi-symptom illness with a multisystem pathogenesis involving alterations in the nervous, endocrine and immune systems.Abnormalities in stress responses have been identified as potential triggers or mediators of CFS symptoms. This study focused on the stress mediator neuropeptide Y (NPY). We hypothesized that NPY would be a useful biomarker for CFS.

METHODS: The CFS patients (n = 93) were from the Chronic Fatigue and Related Disorders Clinic at the University of Miami and met the 1994 case definition of Fukuda and colleagues. Healthy sedentary controls (n = 100)) were from NIH or VA funded studies. Another fatiguing, multi-symptom illness, Gulf War Illness (GWI), was also compared to CFS. We measured NPY in plasma using a radioimmunoassay (RIA). Psychometric measures, available for a subset of CFS patients included: Perceived Stress Scale, Profile of Mood States, ATQ Positive & Negative Self-Talk Scores, the COPE, the Beck Depression Inventory, Fatigue Symptom Inventory, Cognitive Capacity Screening Examination, Medical Outcomes Survey Short Form-36, and the Quality of Life Scale.

RESULTS: Plasma NPY was elevated in CFS subjects, compared to controls (p = .000) and to GWI cases (p = .000). Receiver operating characteristics (ROC) curve analyses indicated that the predictive ability of plasma NPY to distinguish CFS patients from healthy controls and from GWI was significantly better than chance alone. In 42 patients with CFS, plasma NPY had significant correlations (<0.05) with perceived stress, depression, anger/hostility, confusion, negative thoughts, positive thoughts, general health, and cognitive status. In each case the correlation (+ or -) was in the anticipated direction.

CONCLUSIONS: This study is the first in the CFS literature to report that plasma NPY is elevated compared to healthy controls and to a fatigued comparison group, GWI patients. The significant correlations of NPY with stress, negative mood, general health, depression and cognitive function strongly suggest that this peptide be considered as a biomarker to distinguish subsets of CFS.

 

Source: Fletcher MA, Rosenthal M, Antoni M, Ironson G, Zeng XR, Barnes Z, Harvey JM, Hurwitz B, Levis S, Broderick G, Klimas NG. Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome. Behav Brain Funct. 2010 Dec 29;6:76. doi: 10.1186/1744-9081-6-76. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024290/ (Full article)

 

Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs

Abstract:

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression.

Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression.

In a series of studies, commencing in patients with Cushing’s disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide.

In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.

 

Source: Gold PW, Licinio J, Wong ML, Chrousos GP. Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. Ann N Y Acad Sci. 1995 Dec 29;771:716-29. http://www.ncbi.nlm.nih.gov/pubmed/8597444