Chronic Interferon-Alpha Administration Disrupts Sleep Continuity and Depth in Patients with Hepatitis C: Association with Fatigue, Motor Slowing, and Increased Evening Cortisol

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Biological psychiatry (Impact Factor: 9.47). 11/2010; 68(10):942-9. DOI: 10.1016/j.biopsych.2010.04.019
Source: PubMed

ABSTRACT Consequences of chronic exposure to cytokines of the innate immune system on sleep in humans and the association of cytokine-induced sleep alterations with behavior, motor performance, and cortisol secretion are unknown.
Thirty-one patients with hepatitis C without pre-existing sleep disorders underwent nighttime polysomnography, daytime multiple sleep latency testing, behavioral assessments, neuropsychological testing, and serial blood sampling at baseline and after ∼12 weeks of either treatment with the innate immune cytokine interferon (IFN)-alpha (n = 19) or no treatment (n = 12). Fatigue and sleepiness were assessed using the Multidimensional Fatigue Inventory and Epworth Sleepiness Scale.
Interferon-alpha administration led to significant increases in wake after sleep onset and significant decreases in stage 3/4 sleep and sleep efficiency. Rapid eye movement latency and stage 2 sleep were significantly increased during IFN-alpha treatment. Decreases in stage 3/4 sleep and increases in rapid eye movement latency were associated with increases in fatigue, whereas decreases in sleep efficiency were associated with reduced motor speed. Increased wake after sleep onset was associated with increased evening plasma cortisol. Despite IFN-alpha-induced increases in fatigue, daytime sleepiness did not increase. In fact, IFN-alpha-treated patients exhibited decreased propensity to fall asleep during daytime nap opportunities.
Chronic exposure to an innate immune cytokine reduced sleep continuity and depth and induced a sleep pattern consistent with insomnia and hyperarousal. These data suggest that innate immune cytokines may provide a mechanistic link between disorders associated with chronic inflammation, including medical and/or psychiatric illnesses and insomnia, which, in turn, is associated with fatigue, motor slowing, and altered cortisol.

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Available from: Charles L Raison, Jan 16, 2014
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    • "There is a wide variety of adverse effects due to the use of interferon alpha 2a, including flu-like syndrome (unusual tiredness, fever, chills, muscle aches, and joint pain), injection site reaction (redness, pain at the site of injection), proneness to serious infections, new or worsening autoimmune disease 5– 7, myelosuppression 8, 9, depression, suicide, suicidal thoughts, and cardiovascular problems 10, 11 such as hypotension or hypertension, arrhythmia and myocardial infarction. Patients may also suffer from nausea, vomiting, loss of appetite, diarrhea, cough, dry mouth, dizziness, vertigo, sweating, itching, hair loss, fatigue, abdominal pain, constipation, sore throat, insomnia 12, anxiety and numbness. "
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    • "Using a within-subjects design we observed no significant alteration in REM latency after 6 weeks IFN-α treatment (Pers comm, David N Christmas, 2011). Our finding of no decrease in REM latency is similar to an independent study by a different group that observed an REM latency increase during IFN-α treatment.92 The difference between these studies has yet to be explained, but importantly neither observed the decrease in REM latency predicted by the 5HT depletion hypothesis. "
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