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Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue
Nicholas G Dowell1, Ella A Cooper2, Jeremy Tibble3
1Brighton and Sussex Medical School, University of Sussex.
Biological Psychiatry
|July 15, 2015
Summary
Interferon-alpha (IFN-α) treatment for hepatitis C causes fatigue by affecting brain striatal microstructure. This study shows these brain changes predict fatigue but not mood changes, suggesting separate mechanisms for motivation and mood.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Interferon-alpha (IFN-α) is used to treat hepatitis C.
- IFN-α can cause severe behavioral changes, including depression-like symptoms.
- Rapid onset of fatigue suggests early immune-brain pathway involvement, but mood changes appear later.
Purpose of the Study:
- To investigate acute brain changes induced by IFN-α.
- To correlate these brain changes with subsequent behavioral effects like fatigue and mood changes.
- To explore the neurobiological mechanisms underlying IFN-α's behavioral side effects.
Main Methods:
- Prospective study using quantitative magnetization transfer (qMT) imaging.
- Measured acute brain microstructural changes 4 hours after the first IFN-α injection.
- Assessed behavioral and psychological changes at baseline and multiple time points up to 24 weeks.
Main Results:
- IFN-α triggered an acute inflammatory response and fatigue.
- Fatigue peaked 4-12 weeks after treatment initiation, preceding mood changes.
- An acute change in striatal microstructure predicted fatigue development but not mood symptoms.
Conclusions:
- Quantitative magnetization transfer (qMT) imaging serves as a biomarker for central effects of peripheral inflammation.
- The striatum is highly sensitive to IFN-α, and its perturbation is linked to IFN-α-induced fatigue.
- Distinct neural substrates mediate IFN-α's effects on motivation (fatigue) and mood.
