Risk for depression during interferon-alpha treatment is affected by the serotonin transporter polymorphism.
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 (L(G), L(A), 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 L(A) allele was associated with a decreased rate of developing MDD (Mantel-Cox log rank test p < .05) with the L(A)/L(A) 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.
Lotrich
Francis E
FE
Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. lotrichfe@upmc.edu
Ferrell
Robert E
RE
Rabinovitz
Mordechai
M
Pollock
Bruce G
BG
D000483:Alleles; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D003865:Major Depressive Disorder / Q000139:chemically induced* / Q000235:genetics* / Q000523:psychology; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy / Q000523:psychology; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009497:Neurotic Disorders / Q000523:psychology; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011994:Recombinant Proteins; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012890:Sleep / Q000502:physiology
D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA
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