Association between a serotonin transporter gene variant and hopelessness among men in the Heart and Soul Study

Hopelessness is associated with mortality in patients with cardiac disease even after accounting for severity of depression. We sought to determine whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with increased hopelessness, and whether this effect is modified by sex, age, antidepressant use or depression in patients with coronary heart disease.

We conducted a cross-sectional study of 870 patients with stable coronary heart disease. Our primary outcomes were hopelessness score (range 0-8) and hopeless category (low, moderate and high) as measured by the Everson hopelessness scale. Analysis of covariance and ordinal logistic regression were used to examine the independent association of genotype with hopelessness.

Compared to patients with l/l genotype, adjusted odds of a higher hopeless category increased by 35% for the l/s genotype and 80% for s/s genotype (p-value for trend = 0.004). Analysis of covariance demonstrated that the effect of 5-HTTLPR genotype on hopelessness was modified by sex (.04), but not by racial group (p = 0.63). Among men, odds of higher hopeless category increased by 40% for the l/s genotype and by 2.3-fold for s/s genotype (p-value p < 0.001), compared to no effect in the smaller female sample (p = 0.42). Results stratified by race demonstrated a similar dose-response effect of the s allele on hopelessness across racial groups.

We found that the 5-HTTLPR is independently associated with hopelessness among men with cardiovascular disease.