Selective hyper-responsiveness of the interferon system in major depressive disorders and depression induced by interferon therapy.
BACKGROUND
Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood.


METHODS
50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed.


RESULTS
IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients.


CONCLUSIONS
Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders.
Department of Gastroenterology and Hepatology, University Hospital of Essen, Essen, Germany. joerg.schlaak@uni-due.de
Joerg F
JF
Schlaak
Martin
M
Trippler
Carolina
C
Hoyo-Becerra
Yesim
Y
Erim
Bernhard
B
Kis
Bo
B
Wang
Norbert
N
Scherbaum
Guido
G
Gerken
D000328:Adult; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D003865:Major Depressive Disorder / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000378:metabolism* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D017931:DNA Primers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins