Altered Structural Brain Networks Related to Adrenergic/Muscarinic Receptor Autoantibodies in Chronic Fatigue Syndrome

J Neuroimaging. 2020 Nov;30(6):822-827. doi: 10.1111/jon.12751. Epub 2020 Jul 1.


Background and purpose: Recent studies suggest that the autoantibodies against adrenergic/muscarinic receptors might be one of the causes and potential markers of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The purpose of this study was to investigate the structural network changes related to autoantibody titers against adrenergic/muscarinic receptors in ME/CFS by performing a single-subject gray matter similarity-based structural network analysis.

Methods: We prospectively examined 89 consecutive right-handed ME/CFS patients who underwent both brain MRI including 3D T1-wighted images and a blood analysis of autoantibodies titers against β1 adrenergic receptor (β1 AdR-Ab), β2 AdR-Ab, M3 acetylcholine receptor (M3 AchR-Ab), and M4 AchR-Ab. Single-subject gray matter similarity-based structural networks were extracted from segmented gray matter images for each patient. We calculated local network properties (betweenness centrality, clustering coefficient, and characteristic path length) and global network properties (normalized path length λ, normalized clustering coefficient γ, and small-world network value δ). We investigated the correlations between the autoantibody titers and regional gray matter/white matter volumes, the local network properties, and the global network properties.

Results: Betweenness centrality showed a significant positive correlation with β1-AdR-Ab in the right dorsolateral prefrontal cortex. The characteristic path length showed a significant negative correlation with β2-AdR-Ab in the right precentral gyrus. There were no significant correlations between the antibody titers and the regional gray matter/white matter volumes, and the global network properties.

Conclusions: Our findings suggest that β1 AdR-Ab and β2 AdR-Ab are potential markers of ME/CFS.

Keywords: adrenergic/muscarinic receptors; autoantibodies against; myalgic encephalomyelitis/chronic fatigue syndrome; structural network analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / immunology*
  • Cerebral Cortex / diagnostic imaging*
  • Fatigue Syndrome, Chronic / diagnostic imaging*
  • Fatigue Syndrome, Chronic / immunology
  • Female
  • Gray Matter / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Receptors, Adrenergic / immunology*
  • Receptors, Muscarinic / immunology*
  • White Matter / diagnostic imaging
  • Young Adult


  • Autoantibodies
  • Receptors, Adrenergic
  • Receptors, Muscarinic