Insights from metabolites get us closer to a test for chronic fatigue syndrome

Press Release: Columbia University’s Mailman School of Public Health, July 9, 2018. A study led by researchers at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health has identified a constellation of metabolites related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Combining this data with data from an earlier microbiome study, the researchers now report they can predict whether or not someone has the disorder with a confidence of 84 percent.

The research team analyzed blood samples provided by 50 patients with ME/CFS and 50 controls matched for sex and age who were recruited at four clinical sites across the United States. Using mass spectrometry, a laboratory technique used to identify molecules by measuring their mass, the scientists found 562 metabolites — microscopic byproducts of human and microbial processes such as sugar, fat, and protein molecules. They excluded molecules related to antidepressants and other drugs patients might be taking.

Their metabolomics analysis, among the most detailed and meticulous to date, uncovered altered levels of metabolites, including choline, carnitine and several complex lipids present in patients with ME/CFS. The altered metabolites suggest dysfunction of the mitochrondria, the cellular powerplant, a finding in line with those reported by other research teams. Uniquely, the CII study also reports a second distinct pattern of metabolites in patients with ME/CFS and irritable bowel syndrome (IBS), matching earlier findings from their 2017 fecal microbiome study. Half of the patients with ME/CFS also had IBS.

When the researchers combined biomarkers from both the microbiome study and the new metabolome study, they reported a .836 predictive score, indicating an 84 percent certainty as to the presence of ME/CFS — better than with either study alone.

“This is a strong predictive model that suggests we’re getting close to the point where we’ll have lab tests that will allow us to say with a high level of certainty who has this disorder,” says first author Dorottya Nagy-Szakal, MD, PhD, a researcher at CII.

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Meta-analysis investigating post-exertional malaise between patients and controls

Abstract:

Post-exertional malaise is either required or included in many previously proposed case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. A meta-analysis of odds ratios (ORs; association between patient status and post-exertional malaise status) and a number of potential moderators (i.e. study-level characteristics) of effect size were conducted.

Post-exertional malaise was found to be 10.4 times more likely to be associated with a myalgic encephalomyelitis/chronic fatigue syndrome diagnosis than with control status. Significant moderators of effect size included patient recruitment strategy and control selection. These findings suggest that post-exertional malaise should be considered a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome.

Source: Brown A, Jason LA. Meta-analysis investigating post-exertional malaise between patients and controls. J Health Psychol. 2018 Jul 1:1359105318784161. doi: 10.1177/1359105318784161. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29974812

Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome

Abstract:

Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion.

The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest.

Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion.

In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

Source: Andreas Finkelmeyer, Jiabao He, Laura Maclachlan, Andrew M. Blamire, Julia L. Newton. Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome. PLoS ONE. Published: July 3, 2018 https://doi.org/10.1371/journal.pone.0200068 (Full article)

Are ME/CFS Patient Organizations “Militant”?

Abstract:

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a contested illness category. This paper investigates the common claim that patients with ME/CFS—and by extension, ME/CFS patient organizations (POs)—exhibit “militant” social and political tendencies. The paper opens with a history of the protracted scientific disagreement over ME/CFS. We observe that ME/CFS POs, medical doctors, and medical researchers exhibit clear differences in opinion over how to conceptualize this illness.

However, we identify a common trope in the discourse over ME/CFS: the claim of “militant” patient activism. Scrutinizing this charge, we find no compelling evidence that the vast majority of patients with ME/CFS, or the POs representing them, have adopted any such militant political policies or behaviours. Instead, we observe key strategic similarities between ME/CFS POs in the United Kingdom and the AIDs activist organizations of the mid-1980s in the United States which sought to engage scientists using the platform of public activism and via scientific publications.

Finally, we explore the contours of disagreement between POs and the medical community by drawing on the concept of epistemic injustice. We find that widespread negative stereotyping of patients and the marginalization and exclusion of patient voices by medical authorities provides a better explanation for expressions of frustration among patients with ME/CFS.

Source: Blease, C. & Geraghty, K.J. Are ME/CFS Patient Organizations “Militant”? Bioethical Inquiry (2018). https://doi.org/10.1007/s11673-018-9866-5

Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics

Abstract:

The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood.

We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide.

Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

Source: Dorottya Nagy-Szakal, Dinesh K. Barupal, Bohyun Lee, Xiaoyu Che, Brent L. Williams, Ellie J. R. Kahn, Joy E. Ukaigwe, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Bruce Levin, Mady Hornig, Oliver Fiehn & W. Ian Lipkin . Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Scientific Reports, volume 8, Article number: 10056 (2018) https://www.nature.com/articles/s41598-018-28477-9 (Full article)

The Human/Animal Interaction of Chronic Fatigue and Immune Dysfunction Syndrome: A Look At 127 Patients and Their 463 Animals

By R. Tom Glass, D.D.S., Ph.D. Professor Emeritus of Oral and Maxilofacial Pathology and Pathology University of Oklahoma, Health Sciences Center Tulsa, OK 74114

Throughout the recognized existence of Chronic Fatigue and Immune Dysfunction Syndrome, anecdotal reports have linked domestic animals with CFIDS, but no formal scientific studies were reported (1,2). Cats and dogs were implicated by their owners most frequently. The usual association with the presence of the animal in the household of a CFIDS patient, followed by the development of strange diseases or dysfunctions in the animal, many of which mimic CFIDS. The severity of the diseases often necessitated euthanasia. In a fewer number of cases, the onset of CFIDS in the patient was associated with an exposure to a domestic animal which was later found to show signs of CFIDS.

Observations from my animal biopsy service demonstrate two interesting findings in animals of CFIDS patients (unpublished findings). Gingival biopsies from cats demonstrated an unusual epithelial viral vesicle associated with an equally unusual submucosal inflammatory response. Several melanomas were found in dogs of CFIDS patients which had the unique feature of a striking progression of the tumor in the absence of an inflammatory response.

Both dogs and cats are known to be susceptible to a wide range of viruses. With the exception of rabies, no zoonotic (animal to human or human to animal) viral infection transmission has been demonstrated between typical domestic animals and humans (3).

These observations and recognitions prompted the following questions:

  1. Do CFIDS patients have domestic animals (pets)?
  2. What is the interaction between CFIDS patients and their pets?
  3. Do the domestic animals have any clinical signs of CFIDS?
  4. What type of signs or manifestations of CFIDS do animals of CFIDS patients demonstrate?
  5. What is the relationship between the interaction of CFIDS patients and their animals and the onset and course of CFIDS?

and resulted in a series of studies to answer the questions.

The first study was a retrospective study of Center for Disease Control and Prevention (CDC) criteria-met CFIDS patient: using a standardized questionnaire which included patient comments. The study subjects came from a university medical center and CFIDS support groups throughout the United States. Appropriate statistical tests, including mean, median, Z test, multivariant analysis, and Chi-square test, were used. This information was compared to national statistical Information on animal interaction compiled by the American Veterinary Medical Association.

One hundred twenty-seven (127) criteria-met CFIDS patients completed questionnaires on their animal Interactions- There were 114 females and 13 males in the study. All respondents were Caucasian with the exception of one Native American. The mean age of the CFIDS patients was 42.4 years with a median age of 43 years. 61.4% of the respondents were married; 311.6% were either single, divorced, or widowed.

The most striking result of this study was the association between CFIDS patients and animals (usually indoor pets) and the number of animals per CFIDS patient. 97% of the CFIDS patients had animal contact [expected normal contact: 57.9% (4)], with only 2 males and 2 females not reporting animal contact. Reported dog ownership per household for CFIDS males was 9.5 and for CFIDS females was 7.9 (expected national average: 1.52). Reported cat ownership per household for CFIDS males was 6.1 and for CFIDS females was 8.7 (expected national average: 1.95). 106 of the respondents (83.5%) reported that their animals (pets) had atypical diseases with signs and symptoms which mimicked CFIDS in humans. Of these 106 CFIDS patients 100 (94.3%) either were the primary caregiver for the sick animals or had intimate contact (sleeping with, being bitten or scratched by, or kissing the animal). The next most common animal contact was birds (parakeets and ducks were mentioned most often), followed by horses, cows, rabbits, goats, and guinea pigs. Two (2) CFIDS patients had contact with primates. The reported mean age of the dogs was 6 years (median = 6 years); of the cats was 6.2 years (median = 5 years); and of other types of animals was 3.2 years (median = 0.4 years).

All of these differences between expected and observed values were found to be statistically significant (p>001) including a statistically significant higher (.02<p£ 05) possession of cats by single, divorced, and widowed persons than married people. Statistical analysis (Chi-square) of the relationship between intimate contact by CFIDS patients and the presence of CFIDS like signs in their animals was highly significant (p£ 001). 67% of the respondents that had such contact stated that the animal showed CFIDS-like signs prior to the human and 33% of the respondents felt that the otherwise healthy animal contracted its CFIDS signs from the CFDS patient. The place where the pet was obtained was as follows: Friends (35%), Commercial (26%), Stray (21%), Pound (15%), Self-bred (3%), 41% of the CFIDS patients had animals that were still alive while 69% of the CFIDS patients had animals that had either died or were moribund at the time of the survey.

Finally, of equal importance were the CFIDS patient’s comments. These comments were often voluminous and detailed the interaction between the animals and the CFIDS patient. It is very clear that the CFIDS patients, in general, are “animal lovers” even though frquently the patient comments spoke of allergies to animals. Simliarly, the respondents gave excellent descriptions of their animal’s(s’) CFIDS-like signs from time of onset to ultimate temination.Respondents also noted that the animals were often the “living being” most consistently in close contact with the CFIDS patient.

The conclusion of this study was that CFIDS patients not only have pets, but that there is a significant animal interaction and that a large number of these animals have atypical or unusual diseases which at least mimic CFIDS.

In the second study, the CFIDS patients reported on a total of 463 animals: 115 healthy animals (which served as a control group for the study) and 348 animals which showed signs of either dysfunction or disease. The control group was comprised of 51 dogs (44%), 39 cats (34%), and 25 animals that were grouped together as “others”. The “others” group was predominantly large animals: horses, cows, goats, and pigs. All the control animals were still living and well at the time of the survey or had died of either traumatic or natural causes.

The group of animals which showed signs of either dysfunction or disease were made up of 189 dogs (54%), 144 cats (41%), and 15 animals that were grouped together as “others”. This “others” group was predominantly small domestic pets: birds, hamsters, and guinea pigs. The mean age of the dogs in this study was 6.5 years (median 6 years); of the cats was 6.2 years (median = 5 years); and of other types of animals was 3.2 years (median = 0.4 years).

The distribution of signs of the animals showing either dysfunction or disease are as follows: 137 animals (59 cats; 64 dogs; 14 others) were classified as having “General Signs.” 36 animals (15 cats; 14 dogs; 7 others) of the general signs category were classified as being “Sick NOS” because the animals were clearly Ill, but no diagnosis could be or had been rendered by a veterinarian. The “Sick NOS” animals were often described as having the same types of clinical signs as their owner. 26 animals (9 cats; 9 dogs; 7 others) in the general signs category died suddenly of unexplained causes. 26 animals (11 cats; 15 dogs) of the general signs category had a variety of altered immune conditions. including allergies, skin rashes, hair loss, systemic lupus erythematosus, and sneezing. 20 animals (3 cats; 17 dogs) developed Parvo or other viral Infections. 11 animals (9 cats; 2 dogs) transmitted their conditions to other animals either by birth or direct contact. 10 animals (9 cats; 1 dog) were listed as having eaten mice, rats, or other wild animals. 9 animals (3 cats; 6 dogs) had non-viral infections.

122 animals (41 cats; 81 dogs) had “Neurological” signs. 32 animals (17 cat.; 15 dogs) of the neurological category had lethargy, weakness, or sleep disorders. 30 animals (9 cats; 21 dogs) in the neurological category had seizures, tremors, or tail twitching. 19 animals (4 cat:; 15 dogs) demonstrated hind limb dragging, myalgia, arthralgia, or Bell’s palsy. 16 animals (6 cats; 10 dogs) were anxious, depressed, moody, or demonstrated inappropriate behavior, including urination and defecation outside their litterbox. 15 animals (4 cats; 11 dogs) had photophobia, ocular discharge, or blindness. 10 animals (1 cat; 9 dogs) had deafness, ear sensitivity, or loss of balance.

36 animals (21 cat.; 15 dogs) demonstrated “Gastrointestinal” signs. 13 animals (9 cats; 4 dogs) in the gastrointestinal category had inflamed gingiva, mouth odor, tooth loss, or drooling. 10 animal, (4 cats; 6 dogs) in the gastrointestinal category had diarrhea or abdominal distention. 9 animals (5 cat.; 4 dogs) demonstrated anorexia. 3 animals (2 cats; I dog) had increased appetite without weight gain. 1 cat had hard stools.

33 animals (18 cats; 14 dogs; 1 other) showed “Reticuloendothelial or Blood Disorders”. 12 animals (3 cats; 8 dogs; 1 other) of this category demonstrated bleeding or blood disorders. 10 animals (9 cats; I dog) in this category developed leukemia. While all of the leukemic cats were positive for feline leukemia virus [FLV], 5 of the cats had been vaccinated against FLV prior to the onset of their feline leukemia. 7 animals (5 cat.; 2 dogs) died of either feline AIDS or canine immune defidency (AIDS). 2 dogs showed massive and generalized lymphadenopathy. 1 cat and 1 dog died of lymphoma (lymphosarcoma).

Excluding leukemia and lymphoma, 15 animals (3 cats;12 dogs) developed tumors (“Neoplasia”). 8 animals (2 cats; 6 dogs) in this category had either fatal and/or multiple tumors which were not further classified, but which resulted in euthanasia of the animal. 4 dogs of this category died from malignant tumors of epithelial origin (3 squamous cell carcinomas and 1 transitional cell carcinoma), while 1 cat developed perianal adenomas, but was still living at the time of the survey. 1 dog died of a functional pituitary tumor and 1 dog died of melanoma.

Only 5 animals (2 cats; 3 dogs) were reported to have “Endocrine Disorders”. 2 cats and 2 dogs in this category had thyroid hyperplasia or thyroid nodules and 1 dog has pituitary hyperplasia.

Of equal importance, 113 of the 127 patients 89%) stated that their own CFIDS symptoms directly related their interaction with animals. Specifically, 79 of the respondents (71%) stated that they either had contact with multiple animals, were farmers, or were caretakers of multiple animals. 18 of these CFIDS patients (16%) note that the onset of their CFIDS symptoms were temporarily associated with the obtaining of a new pet, while 2 CFID patients (1%) noted that their CFIDS symptoms improved after the pet left or died. 9 respondents (8%) stated the other family members also contracted CFIDS in such manner as to implicate the pet as being possibly a common link in etiology. 3 CFIDS patients noted that the onset their CFIDS symptoms directly followed a flea bite episode and 2 CFDS patients reported that the prior owner of the home in which they contracted their CFIDS was inhabited by both CFIDS patients and sick animals.

As was noted in the first study, CFIDS patients care deeply for their animals. This observation can be understood by the detail and thoroughness with which the CFIDS patients filled out the information concerning the symptoms, laboratory results (such as blood count., blood chemistries, biopsy reports, etc.) and the courses of the animal’s(s’) condition. For the most part, it was the CF1DS patient who filled out the questionnaire. It must be remembered that these patients usually have severe fatigue and for them to have given such attention to detail was a major task.

Both studies also noted what an important role the pet plays in the CFIDS patient’s life. An analysis of the comments by the CFDS patients demonstrates unequivocally that the pet was often the CFIDS patient’s major contact with a living being. While it is imperative to consider the results of this study, it is equally imperative not to isolate CFIDS patients from their pets Rather, prevention of intimate contact, such as sharing food or kissing between the CFIDS patient and the pet, should be encouraged.

While the results of this study have certain subjective elements, such as reliance upon CFIDS patient and fault observations or the possibility of “symptom transference” (e.g., arthralgia in a pet is more likely to be noted by an arthralgic patient than a person free of joint pain), the recurrent finding of certain symptoms that may be common to both the CFIDS patient and the animal warrant attention It is important to consider the possibility that CFIDS may be transmitted from human to animal and/or from animal to human. If one considers the symptom of lethargy in the animals, the 32 CFIDS patients who observed this symptom all noted that the lack of energy was different than they had observed before in either the affected animal or in other animals in the same household who did not demonstrate the symptom. The seizure disorders and sudden unexplained deaths were more dramatic and objective signs of possible transmission of an agent that affects the nervous system. While seizure disorders and sudden unexplained deaths are not accepted features of CFIDS in humans, others have noted anecdotally a higher than usual number of seizure disorders and even sudden unexplained deaths in CFIDS patients.

While this study demonstrates the multiplicity of CFIDS-like signs in the animals, it is this same multi-organ involvement in the CFIDS patients that makes CFIDS so difficult to diagnose in humans. As with CFIDS in humans, the animals usually showed no laboratory evidence of a specific disease entity. There was, however, a predominance of neumlogic, neuromuscular, and rheumatologic symptoms in the animals just as there are in CFIDS patients. The result of these studies need to alert the veterinary profession of the need to inquire as to the health of the animal owner and their family. Conversations with a number of clinical veterinarians have pointed out that they are commonly confronted with conditions in domestic animals which do not fall into well established disease patterns. The most common of these deal with neurological and infectious diseases. These two areas were the most often reported as the pet signs found by CFIDS patients. Somewhat confounding was the low number of animals demonstrating endocrine disease. This under-reporting may be more of a lack of testing than a lack of disease as these tests are expensive and CFIDS patients are often financially unable to afford their own diagnostic tests., much less their animal’s(s’).

The results of these studies also need to alert the veterinaray profession that should there be a possibility of animal to human transmission of CFIDS, veterinarians might want to consider the wearing of protective clothing, gloves, eyewear, and masks when examining animals. We have received a number of reports from veterinarians around the country, especially from female veterinarians, that they have had to substantially limit their practices due to fatigue and other CFIDS-like symptoms. Similarly, precautions need to be taken to prevent CFIDS from being transmitted from one animal to another.

The conclusions of the second study were that animals of CFIDS patients demonstrated a wide range of disease and dysfunctional signs, similar to their CFIDS owners. The interactions between the animal and the CFIDS patients was often intimate. The study showed that the course of CFIDS in the animals varied widely, but after more thorough analyses of the data and of subsequent data, it appears that the animals have two distinct courses: 1. Their CFIDS signs produce progressive deterioration and the animal dies or 2. The animals appear to completely recover, usually after about five years.

In closing, both of the above studies had one common conclusion: animal interaction is a very important part of CFIDS patients’ lives’. I am often asked by CFIDS patients, knowing what I do about the CFIDS patient/animal interaction, if I would recommend that CFIDS patients have pets. While there is no way for me to survey animals, from my interaction with my own pet. and with the way CFIDS patients love their pets’ I would say that any pet would willingly run the risk of contracting CFIDS for the love, care and attention they will receive from CFIDS patients.

REFERENCES:

1. Ostrom, N. 50 Things You Should Know About the Chronic Fatigue Syndrome: New York: That New Magazine, 1992: pp 25, 26, 36, 37

2. Ostrom, N. What Really Killed Gilda Radner? New York: That New Magazine, Inc., 1991 pp. 159-164, 345-352

3. Cotran, RS., Kumar, V., Robbins, SL. Robbins Pathological Basis of Disease, 4th ed. Philadelphia: W. B. Saunders Co., 1989; pp. 309-310

4. Wise, JK. The Veterinary Sevice Market for Companion Animals. Schaumburg, IL; American Veterinary Association, 1992; pp. 5-65.

AUTHORS NOTE: This article is the first of three articles on my experiences with Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS; aka CFS). The first article deals with the interaction between CFIDS patients and their animals. The second article will deal with the actual autopsy findings of sick animals owned by CFIDS patients, the transmission of the CFIDS infectious agent to healthy animals, and the autopsy results of these animals. The third article will deal with the oral and head and neck manifestations of CFIDS, a lip biopsy of minor salivary glands for the confirmation of CFIDS, and some interesting therapy for the head and neck pain so often experienced by CFIDS patients [The second and third articles by Dr. Glass will he published in the next two consecutive issues of MPWC News – Ed. note.] In the early 1990’s, the following studies were conducted on CFIDS patients and their animals. The articles were sent to a number of both medical joumals and veterinary medical journals. The response from the editor of the medical journals was that while the articles were well-written, thorough and timely, they were better placed in veterinary medical journals. The veterinary medical joumal editors agreed with the medical journal editors in terms of the validity of the studies; however, they felt that if they published the articles, they might jeopardize the entire practice of veterinary medicine as small animals comprise the largest segments of such practices.

Source: This article appeared in the Spring 1998 Vol 3 Number 2 Edition of the Medical Professionals With CFIDS (MPWC) News

The “Biology-First” Hypothesis: Functional disorders may begin and end with biology-A scoping review

Abstract:

While it is generally accepted that gastrointestinal infections can cause functional disturbances in the upper and lower gastrointestinal tract-known as postinfectious irritable bowel syndrome (PI-IBS) and functional dyspepsia (PI-FD)-it has still not been widely recognized that such an infection can also initiate functional non-intestinal diseases, and that non-intestinal infections can provoke both intestinal and non-intestinal functional disturbances. We conducted a scoping review of the respective literature and-on the basis of these data-hypothesize that medically unexplained functional symptoms and syndromes following an infection may have a biological (genetic, endocrine, microbiological) origin, and that psychological and social factors, which may contribute to the disease “phenotype,” are secondary to this biological cause. If this holds true, then the search for psychological and social theories and factors to explain why one patient develops a chronic functional disorder while another does not is-at least for postinfectious states-misleading and detracts from exploring and identifying the true origins of these essentially biological disorders. The biopsychosocial model may, as the term implies, always begin with biology, also for functional (somatoform) disorders.

Source: Enck P, Mazurak N. The “Biology-First” Hypothesis: Functional disorders may begin and end with biology-A scoping review. Neurogastroenterol Motil. 2018 Jun 28:e13394. doi: 10.1111/nmo.13394. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29956418

Liver volume is lower and associates with resting and dynamic blood pressure variability in chronic fatigue syndrome

Abstract:

Background: Chronic fatigue syndrome (CFS) in many cases is characterised by abnormal autonomic function and lower blood pressure (BP). In animals the liver is a capacitance vessel for BP homeostasis. We developed a novel liver magnetic resonance (MR) imaging technique to compare liver volume in CFS to controls, and to explore its role in cardiovascular physiology.

Methods: Liver MR (single breath-hold, enhanced T1-weighted, high-resolution isotropic volume excitation 3-Tesla Achieva, NL) determined liver volume. Red cell and plasma volume were also measured. A 10 min resting cardiac autonomic assessment using beat-to-beat measurement (Taskforce; CNSystems) was followed by assessment of hemodynamic response to standing to determine blood pressure drop and return to baseline.

Results: Forty-four CFS patients (age = 45.5, 34f/10 m, Fukuda criteria) and 10 age, activity and sex matched controls (age = 49.4, 7f/3 m) participated. Adjusted for body size, CFS patients had significantly reduced liver volumes (775 (101) ml/m2 v 846 (96) ml/m2; p = 0.02). At rest, liver volume was unrelated to symptom severity, heart rate, BP or heart rate variability. Both increased systolic and diastolic low frequency (LF) BP variability (predominantly sympathetic) were associated with lower liver volumes. On standing, liver volume was unrelated to BP drop but was associated with successful BP return-to-baseline. Red cell and plasma volume were associated positively with liver volume. Multivariate analysis confirmed return-to-baseline BP on standing which was independently associated with liver volume.

Conclusion: Liver volumes were smaller in CFS compared to controls. The relationship between return-to-baseline BP after standing and liver volume suggests, as in animals, that the liver is involved in maintenance of BP.

Abbreviations: ACI: Accelerated cardiac index; BPV: Blood pressure variability; BRS: Baroreflex sensitivity; CFS: chronic fatigue syndrome; Chr: Chromium; CI: cardiac index; FIS: Fatigue impact scale; HF: High frequency; HRV: Heart rate variability; LF: Low frequency; MR: magnetic resonance; NU: normalised units; SD: Standardised deviation; PSD: power spectral density; SI: Stroke index; TPRI: Total peripheral resistance index

SourcePawel Zalewski, Andreas Finkelmeyer, James Frith, Laura Maclachlan, Andrew Blamire & Julia L. Newton (2018) Liver volume is lower and associates with resting and dynamic blood pressure variability in chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2018.1488525