Background
Major depressive disorder (MDD) occurs in a subset of patients receiving interferon-alpha
treatment, although many are resilient to this side effect. Genetic differences in
the serotonin reuptake transporter promoter (5-HTTLPR) may interact with the inflammatory
system and influence depression risk.
Methods
A cohort of 71 nondepressed hepatitis C patients about to receive interferon-alpha
was prospectively followed, employing a diagnostic structured clinical interview (Structured
Clinical Interview for DSM-IV Axis I Disorders [SCID-I]) and self-report questionnaires.
Patients were genotyped for the 5-HTTLPR (LG, LA, and S) and the variable number of tandem repeats (VNTR) polymorphism in the second
intron. Kaplan-Meier analyses were used to compare major depression incidence. Genotype
effects on sleep quality (Pittsburgh Sleep Quality Index) and Beck Depression Inventory
(BDI) were assessed using mixed-effect repeated-measure analyses.
Results
The LA allele was associated with a decreased rate of developing MDD (Mantel-Cox log rank
test p < .05) with the LA/LA genotype being the most resilient. This genotype was also associated with better
sleep quality [F(61.2,2) = 3.3, p < .05]. The ability of baseline sleep quality to predict depression incidence disappeared
when also including genotype in the model. Conversely, the relationship of neuroticism
with depression incidence (B = .07, SE = .02, p < .005) was not mitigated when including genotype.
Conclusions
Using a prospective design, 5-HTTLPR is associated with MDD incidence during interferon-alpha
treatment. Preliminary evidence that this effect could be mediated by effects on sleep
quality was observed. These findings provide support for a possible interaction between
inflammatory cytokine (interferon-alpha) exposure and 5-HTTLPR variability in MDD.
Key words
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Article info
Publication history
Published online: September 19, 2008
Accepted:
August 7,
2008
Received in revised form:
August 7,
2008
Received:
April 29,
2008
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
