Molecular Neurobiology

, Volume 53, Issue 4, pp 2550–2571

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

  • Gerwyn Morris
  • Michael Berk
  • Ken Walder
  • Michael Maes
Article

DOI: 10.1007/s12035-015-9262-7

Cite this article as:
Morris, G., Berk, M., Walder, K. et al. Mol Neurobiol (2016) 53: 2550. doi:10.1007/s12035-015-9262-7

Abstract

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

Keywords

Immune Inflammation Oxidative stress Toll-like receptor Cognition Depression Chronic fatigue syndrome Neurology Psychiatry 

Abbreviations

CFS

Chronic fatigue syndrome

TNFα

Tumor necrosis factor

IL

Interleukin

NF-ΚB

Nuclear factor-ΚB

IFN

Interferons

TLR

Toll-like receptors

PAMPs

Pathogen-associated molecular patterns

DAMPs

Damage-associated molecular patterns

MAPK

Mitogen-activated protein kinase

ROS

Reactive oxygen species

RNS

Reactive nitrogen species

4-HNE

4-Hydroxynonenal

MDA

Malondialdehyde

EBV

Epstein-Barr virus

CAEBV

Chronic activated Epstein-Barr virus syndrome

ME

Myalgic encephalomyelitis

CEBVS

Chronic EBV syndrome

MS

Multiple sclerosis

MSRV

MS retrovirus

HHV

Human herpes virus

Th2

T helper 2

DCs

Dendritic cells

Bcl2

B cell lymphoma 2

BAX

Bcl-2-associated X protein

PCR

Polymerase chain reaction

NS1

Nonstructural protein

CNS

Central nervous system

CSF

Cerebrospinal fluid

TGF-β1

Transforming growth factor β1

MRI

Magnetic resonance imaging

HCMV

Human cytomegalovirus

Nrf2

Nuclear factor erythroid 2 [NF-E2]-related factor 2

mTOR

Mammalian target of rapamycin protein

Bf

Borrelia burgdorferi

PG

Prostaglandin

ERK

Extracellular signal-regulated kinase

COX-2

Cyclooxygenase 2

SC

Stachybotrys chartarum

NADH

Reduced nicotinamide adenine dinucleotide

JNK

c-Jun N-terminal kinase

FoxP3

Forkhead box P3

DON

Vomitoxin or deoxynivalenol

STAT3

Signal transducer and activator of transcription 3

iNOS

Inducible nitric oxide synthase

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Gerwyn Morris
    • 1
  • Michael Berk
    • 2
    • 3
  • Ken Walder
    • 4
  • Michael Maes
    • 2
    • 5
  1. 1.Tir Na NogLlanelliUK
  2. 2.IMPACT Strategic Research Centre, School of MedicineDeakin UniversityGeelongAustralia
  3. 3.Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia
  4. 4.Centre for Molecular and Medical Research, School of MedicineDeakin UniversityGeelongAustralia
  5. 5.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand

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