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Acute changes in striatal microstructure predict the development of interferon-alpha induced fatigue

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posted on 2023-06-08, 22:16 authored by Nicholas DowellNicholas Dowell, Ella A Cooper, Jeremy Tibble, Valerie Voon, Hugo CritchleyHugo Critchley, Mara Cercignani, Neil Harrison
BACKGROUND Interferon-alpha (IFN-a) is a key mediator of antiviral immune responses used clinically for hepatitis C treatment. Though effective, IFN-a induces marked behavioral changes that, when severe, can appear indistinguishable from major depression. Curiously, fatigue and motivational impairment evolve rapidly, suggesting acute engagement of immune-brain communicatory pathways, yet mood impairments typically emerge later, after weeks of treatment. Whether this reflects prolonged modulation of motivational processes underpinning fatigue or separate neurobiological mechanisms is currently unclear. METHODS Here, we used quantitative magnetization transfer (qMT) imaging, an advanced microstructural neuroimaging technique sensitive to effects of inflammation, in a prospective study design to measure acute brain changes to IFN-a and relate these to later development of discrete behavioral changes. Twenty-three patients initiating IFN-a treatment for hepatitis C underwent qMT imaging and blood sampling at baseline and 4 hours after their first IFN-a injection. Comprehensive behavioral and psychological assessments were completed at both scanning sessions and at treatment weeks 4, 8, 12, and 24. RESULTS IFN-a injection stimulated an acute inflammatory cytokine response and evoked fatigue that peaked between 4 and 12 weeks, preceding mood change by 4 weeks. In the brain, IFN-a induced an acute change in striatal microstructure that additionally predicted development of fatigue but not mood symptoms. CONCLUSIONS Our findings highlight qMT as an in vivo biomarker of central effects of peripheral inflammation. We demonstrate exquisite sensitivity of the striatum to IFN-a, implicate striatal perturbation in IFN-a-induced fatigue, and dissociate this from mechanisms underlying IFN-a-induced mood symptoms, providing empirical support for distinct neural substrates mediating actions on motivation and mood.

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Publication status

  • Published

File Version

  • Published version

Journal

Biological Psychiatry

ISSN

0006-3223

Publisher

Elsevier

Issue

4

Volume

79

Page range

320-328

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-09-15

First Open Access (FOA) Date

2015-09-15

First Compliant Deposit (FCD) Date

2015-09-15

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