Interferon-alpha-Induced Changes in NODDI Predispose to the Development of Fatigue

Neuroscience
Nicholas G DowellNeil A Harrison

Abstract

Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. In susceptible patients, fatigue and motivational impairment emerge early and have been linked to changes in basal ganglia (striatal) metabolism, neurochemistry and microstructural integrity. Here we use neurite orientation dispersion and density imaging (NODDI) modeling of multi-shell diffusion MRI to investigate whether changes in orientation-dispersion index (ODI) or neurite density index (NDI) can predict the later emergence of IFN-α-induced fatigue. Eighteen patients initiating IFN-α-based treatment for hepatitis-C underwent diffusion MRI and blood sampling at baseline and 4 h after their first IFN-α injection. They were then followed up with regular psychological assessments for 12 weeks of treatment. IFN-α injection stimulated an acute inflammatory cytokine response and evoked acute fatigue that peaked between 4 and 12 weeks of treatment. Within the brain, IFN-α induced an acute increase in NDI in patients that exper...Continue Reading

Citations

Oct 26, 2018·Arthritis Care & Research·David S PisetskyJennifer L Rogers
Nov 5, 2019·Rheumatology·S Mechiel Korte, Rainer H Straub
Mar 7, 2019·Frontiers in Neuroscience·Sue Y YiJohn-Paul J Yu
Aug 20, 2020·Journal of Neuroscience Methods·Kouhei KamiyaShigeki Aoki
Jul 1, 2021·Oxford Open Immunology·Valeria Mondelli, Carmine M Pariante

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Methods Mentioned

BETA
ELISA
ELISAs

Software Mentioned

MCFLIRT
Matlab
NODDI
Advanced Normalization Tools ( ANTs
correct
FSL FMRIB Software Library
SPSS
NODDImatlab
eddy

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