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

•NODDI, was used to probe subtle changes to tissue microstructure associated with IFN-α.•We found a strong correlation between changes in neurite density index with acute and long-term fatigue following IFN-α.•This observation confirms that the striatum is a key brain area targeted by IFN with impli...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Neuroscience Ročník 403; s. 111 - 117
Hlavní autoři: Dowell, N.G., Bouyagoub, S., Tibble, J., Voon, V., Cercignani, M., Harrison, N.A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Ltd 01.04.2019
Elsevier Science
Témata:
Brain - diagnostic imaging
cytokine
Cytokines - blood
depression
Depression - blood
Depression - diagnostic imaging
Depression - immunology
Diffusion Magnetic Resonance Imaging - methods
diffusion MRI
fatigue
Fatigue - blood
Fatigue - diagnostic imaging
Fatigue - etiology
Fatigue - immunology
Female
Hepatitis C - blood
Hepatitis C - diagnostic imaging
Hepatitis C - immunology
Hepatitis C - therapy
Humans
Immunologic Factors - adverse effects
Immunologic Factors - therapeutic use
inflammation
Inflammation - blood
Inflammation - diagnostic imaging
Inflammation - immunology
Inflammation - therapy
Interferon-alpha - adverse effects
Interferon-alpha - therapeutic use
Male
Middle Aged
Neurites
Prospective Studies
Treatment Outcome
cytokine
MRI
MT
FDG
ROI
TNF
IFN-α
HAMD
NDI
fatigue
FWE
ODI
inflammation
NODDI
diffusion MRI
depression
ISSN:0306-4522, 1873-7544, 1873-7544
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:•NODDI, was used to probe subtle changes to tissue microstructure associated with IFN-α.•We found a strong correlation between changes in neurite density index with acute and long-term fatigue following IFN-α.•This observation confirms that the striatum is a key brain area targeted by IFN with implications for impaired motivation. 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 experienced a simultaneous increase in IFN-α-induced fatigue but not in patients that did not. Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8 weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0306-4522
1873-7544
1873-7544
DOI:10.1016/j.neuroscience.2017.12.040