Genetic Predictors of Depressive Symptoms Among Patients Treated With Interferon-α

Investigators:

Amira Pierucci-Lagha, Jonathan Covault, Herbert Bonkovsky, Elizabeth Wright, and Henry R. Kranzler

Hypotheses/Aims

This study will examine the hypothesis that polymorphisms associated with genes encoding proteins that play a central role in serotonin neurotransmission (e.g., the serotonin transporter protein), and arachidonic acid (AA) metabolism [e.g., fatty acid co-enzyme A ligase 4 (FACL4)], moderate the effect of interferon-α (IFN-α) therapy on mood symptoms.

This proposal will employ a pharmacogenetic approach to address the following specific aims:

1. To determine whether alleles at two candidate genes implicated in susceptibility to depression predict a depressive response among patients treated with IFN-α. We hypothesize that patients who are homozygous for the L allele at a polymorphic site in the promoter region of the gene encoding the serotonin transporter, or who have the intron 1 T-allele variant of FACL4 will have a significantly greater depressive response to treatment with IFN-α therapy than patients without these genotypes.
2. To determine whether these genotypic predictors have an additive or interactive effect on the depressive response to IFN-α treatment. We hypothesize that the effects of these genes will be additive, such that subjects with the risk-associated genotype for both of these candidate genes will have the highest risk of depression during IFN-α treatment.

The ultimate goal of this research is to identify individuals who may be at increased risk for the development of depression secondary to IFN-α therapy and who may benefit from prophylactic antidepressant treatment.