Plasma Neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome, 2010, Fletcher et al

Discussion in 'ME/CFS research' started by Hutan, May 14, 2020.

  1. Hutan

    Hutan Moderator Staff Member

    Aotearoa New Zealand

    • Abstract
      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.

      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.

      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.

      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.

      Link: (free access)

      PR thread:

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  2. Hutan

    Hutan Moderator Staff Member

    Aotearoa New Zealand
    It's unclear to me from the other papers quoted on the PR thread if high NPY is a problem or an indication of healthy coping with stress (i.e. NPY seemed to be low in people who had experienced repeated exposure to trauma/ had PTSD) - or doesn't really tell us much at all about coping with stress.

    I'm interested to know if there has been any follow-up work on NPY. Or was it one of the many 'biomarkers!!!!' that have since sunk without a trace?
    Last edited: May 14, 2020
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  3. Hutan

    Hutan Moderator Staff Member

    Aotearoa New Zealand
    Screen Shot 2020-05-15 at 3.47.56 AM.png

    From the paper. NPY levels don't look very different in CFS than in the healthy controls or GWI to me - there's a massive amount of overlap.

    (I understand the title of the paper only claims NPY to be a biomarker of symptom severity in ME/CFS, rather than a biomarker of ME/CFS.)
  4. Hutan

    Hutan Moderator Staff Member

    Aotearoa New Zealand
    Symptom severity was assessed with the following measures:

    "On a subset of 42 CFS cases in this study, perceptions of general health and well-being, severity of clinical symptoms of fatigue, stress, cognitive difficulties, psychological distress and maladaptive coping were assessed using the following self-report measures:

    • The Medical Outcomes Survey Short Form-36 (SF-36) assessed health-related quality of life including: limitations in social activities, emotional problems and general health [37].

    • The Perceived Stress Scale (PSS) was used as a measure of stress [38].

    • The Fatigue Severity Inventory (FSI) was designed for measuring fatigue severity. Items in the inventory are statements related to fatigue perceptions [39].

    • The COPE, a multidimensional coping inventory, was used to assess the different ways in which people respond to stress [40]. Subscales for denial, behavioral disengagement and self-blame were used.

    • The Quality of Life Scale (QOL) total score measured general well-being, cognitive functioning, affective status, physical health status and social activity [41].

    • The Profile of Mood States (POMS) a measure of psychological distress consists of 65 adjectives rated on a 0-4 scale that are comprised of subscales measuring 'depression-dejection', 'tension-anxiety', 'anger-hostility', 'confusion-bewilderment', 'vigor-activity' and 'fatigue-inertia' [42].

    • The Adult Temperament Questionnaire (ATQ) is a 77-item self-report instrument used for assessment of positive and negative thoughts and is a measure of stre ss that is possibly predictive of stress-related health problems [43].

    • The Cognitive Capacity Screening Examination (CCSE) was used to quantify the general cognitive status of subjects [44].

    • The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory used to measure severity of depression [45]."
    If any measures relating to physical symptoms were included (e.g. as part of the SF-36), they didn't make it to the results table of correlations between NPY and 'measurements reflective of symptom severity'.

    Table 3 Pearson Correlations (with p < 0.1) of Measurements Reflective of Symptom Severity and Plasma Neuropeptide Y in CFS cases
    Screen Shot 2020-05-15 at 4.16.43 AM.png
  5. Andy

    Andy Committee Member

    Hampshire, UK
    Just looking at this, unrelated, review, it probably didn't get any further as a biomarker as it wasn't specific enough, at a guess.
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  6. spinoza577

    spinoza577 Senior Member (Voting Rights)

    My constant impression from my own experience and from forums is that there are not such negative thoughts, and that there is no depression. It might be not representative, but also this nice ME video #23 from a few days ago doesn´t indicate any depression or negative thoughts in these PwME.

    I would think, agreeing with @Andy, that NPY may be too unspecific and is probably not already well enough understood.

    Nevertheless, if it will be possible to say: "If ME/CFS, then NPY indicates severity in this illness." it would be fine.
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  7. stuck

    stuck Established Member

    When they talk about these neuropeptides in plasma it falls back on the inflammation studies Younger was/is doing to measure what is overexpressing and the systems out of whack.

    Still feels like a pump signal is backwards to me, even though I'm not educated in this.

    There was a new article that makes me wonder about how signalling gets messed up in these channels and pathways, why laying down is essential for me to function, why it matters to put pressure on the sinus and brainstem, why the 'be dormant' is the 'normal' signal in our brains and how it could be changed with a bit of brain signal tinkering.

    Could the pores be juiced to change the signal? This article seems to suggest TFP does something in one dose. Is this a new approach to an old problem or is it tried-and-failed already?

    'Cell pores' discovery gives hope to millions of brain and spinal cord injury patients

    by Aston University

    May 14, 2020

    Scientists have discovered a new treatment to dramatically reduce swelling after brain and spinal cord injuries, offering hope to 75 million victims worldwide each year.

    The breakthrough in treating such injuries—referred to as central nervous system (CNS) edema—is thought to be hugely significant because current options are limited to putting patients in an induced coma or performing risky surgery.

    The researchers used an already-licensed anti-psychotic medicine—trifluoperazine (TFP) - to alter the behaviour of tiny water channel 'pores' in cells known as aquaporins.

    Testing the treatment on injured rats, they found those animals given a single dose of the drug at the trauma site recovered full movement and sensitivity in as little as two weeks, compared to an untreated group that continued to show motor and sensory impairment beyond six weeks after the injury.

    The treatment works by counteracting the cells' normal reaction to a loss of oxygen in the CNS—the brain and spinal cord—caused by trauma. Under such conditions, cells quickly become 'saltier' because of a build-up of ions, causing a rush of water through the aquaporins which makes the cells swell and exerts pressure on the skull and spine. This build-up of pressure damages fragile brain and spinal cord tissues, disrupting the flow of electrical signals from the brain to the body and vice versa.

    But the scientists discovered that TFP can stop this from happening. Focusing their efforts on important star-shaped brain and spinal cord cells called astrocytes, they found TFP prevents a protein called calmodulin from binding with the aquaporins. Normally, this binding effect sends the aquaporins shooting to the surface of the cell, letting in more water. By halting this action, the permeability of the cells is reduced.

    Journal article: Cell (2020).

    DOI: 10.1016/j.cell.2020.03.037
  8. stuck

    stuck Established Member

    I meant to start that last comment with "in my thought process"... and did some quick look ups on that TFP they suggest -- it's NOT a "nice" drug, but maybe the components can be analyzed to understand why it works on some things. An excerpt of wiki: It has been experimentally used as a drug to kill eukaryotic pathogens like fungi and amoebozoa in humans.[5]
    Which fed my wondering about being infected by some pathogen not yet understood...
    So I'll just now wait for Jonathan to explain why it's wrong and keep "stucking" around. :/
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  9. Cytokinda

    Cytokinda Established Member

    NPY popped up on my radar recently too, though not from this^ study.

    <consults notes>
    It seems I fell down a rabbit hole after reading Cort's recent piece about the NZ researchers looking at a PVN theory:

    Down that rabbit hole I stumbled upon:
    Endocannabinoid and Nitric Oxide Systems of the Hypothalamic Paraventricular Nucleus Mediate Effects of NPY on Energy Expenditure

    And this study that states neuropeptide y may be a mast cell activator:
    Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders

    Based on the study at the top of this thread, I agree with others that NPY doesn't seem particularly useful on its own. However, if it's available clinically, it can be tracked by individuals as they try different treatments. It does seem to be available via Quest (USA):
    Quest NPY

    "Neuropeptide Y is a 36 amino acid peptide very similar throughout all species of mammals. It is found primarily in the sympathetic nervous system, gut and brain. Neuropeptide Y is closely related structurally to Peptide YY and Vasoactive Intestinal Polypeptide. Neuropeptide Y has key roles in cardiovascular and hypothalamic function. It potentiates vasoconstriction, causing an increase in blood pressure. Levels are increased by stress, Dexamethasone, septic shock, relaxation of colon, Atrial Natriuretic Factor, water and sodium secretion, Luteinizing Hormone and ACTH. Levels are inhibited by Amphetamines, and are decreased in patients with Alzheimer's disease. Neuropeptide Y inhibits Norepinephrine, the effect of Cholecystokinin, Renin release, Insulin and Glucagon secretion, and the Melanotropins. Actions of Y are enhanced by a2 adrenoreceptor agonists."

    Sorry, I'm too foggy right now to deconstruct/analyze these shares; I just wanted to post some NPY links while I still remember that I ever read anything about it.
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