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Author Notes:

Jennifer C. Felger, Ph.D., Winship Cancer Institute, Emory University School of Medicine, 1365-B Clifton Road, 5th Floor, Atlanta, GA 30322; jfelger@gmail.com.

All authors declare that there are no conflicts of interest, and all financial disclosures are listed for each author: Charles L. Raison serves as a consultant for Pamlab LLC and Biolex Therapeutics; Andrew H. Miller has served as a consultant for Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Lundbeck Research USA, F. Hoffmann-La Roche Ltd., Schering-Plough Research Institute and Wyeth/Pfizer Inc. and has received research support from Centocor Inc., GlaxoSmithKline, and Schering-Plough Research Institute; Jennifer C. Felger, Steve W. Cole, Thaddeus W. W. Pace, Bobbi J Woolwine, Gregory H. Doho, and Fang Hu have nothing to declare.


Research Funding:

This study was supported in part by grants from the National Institutes of Health to CLR (K23 MH064619, R01 MH070553); AHM (K05 MH069124, R01 HL073921, MHR01MH075102, T32 MH020018); and JCF (F32 MH093054) as well as the Emory Center for AIDS Research (P30 AI050409); and the Cancer Genomics Shared Resource of the Emory University School of Medicine.

In addition, the study was supported by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program; and PHS Grant M01 RR0039 from the General Clinical Research Center program, National Institutes of Health, National Center for Research Resources.


  • Social Sciences
  • Science & Technology
  • Life Sciences & Biomedicine
  • Psychology, Clinical
  • Psychiatry
  • Psychology
  • Depression
  • fatigue
  • gene array
  • interferon-alpha
  • 2 '-5 '-oligoadenylate synthetase

Molecular signatures of peripheral blood mononuclear cells during chronic interferon-alpha treatment: relationship with depression and fatigue


Journal Title:

Psychological Medicine


Volume 42, Number 8


, Pages 1591-1603

Type of Work:

Article | Post-print: After Peer Review


Background: Interferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cells in vivo and its relationship to IFN-α-induced behavioral changes. Method: Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-α therapy (n=10) or at 12 weeks of IFN-α treatment (n=11). Results: Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2′-5′-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-α-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-α-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-α signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-α-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-α and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression. Conclusions: Depression and fatigue during chronic IFN-α administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

Copyright information:

© 2011 Cambridge University Press.

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