Interferon- α induced fatigue is predicted by acute changes in stratal magnetisation transfer (qMT)

• Published in: Brain, behavior, and immunity behavior, and immunity, 2015-10, Vol.49, p.e40-e40
• Main Authors: Harrison, N.A, Dowell, N, Cooper, E, Tibble, J, Voon, V, Cercignani, M, Critchley, H
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591
• DOI: 10.1016/j.bbi.2015.06.151

Interferon- α (IFN- α ) is a key mediator of antiviral immune responses used clinically for Hepatitis-C treatment. Though effective, IFN- α induces marked behavioral changes that can appear indistinguishable from major depression. Fatigue and motivational impairment evolve rapidly, suggesting acute engagement of immune-brain communicatory pathways, yet mood impairments only emerge after weeks of treatment. Whether this reflects prolonged modulation of motivational processes underpinning fatigue or separate neurobiological mechanism is unclear. We used quantitative magnetization transfer imaging (qMT), an advanced microstructural neuroimaging technique sensitive to inflammation, in a prospective study design to measure acute brain changes to IFN- α and relate these to later behavioral changes. Twenty-three patients initiating IFN- α treatment for Hepatitis-C underwent qMT and blood-draw at baseline and 4-hours after their first IFN- α injection. Psychological assessments were completed at both scanning sessions, and treatment weeks 4, 8, 12, 24. IFN-alpha 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- α -induced an acute change in striatal microstructure that predicted development of fatigue, but not mood symptoms. These findings highlight qMT as an in-vivo biomarker of central effects of peripheral inflammation. They demonstrate exquisite sensitivity of striatum to IFN- α , implicate striatal perturbation in induced fatigue, and dissociate this from mechanisms underlying mood symptoms providing empirical support for distinct mechanisms mediating action on motivation and mood.