Association of a serotonin transporter polymorphism (5-HTTLPR) with depression, perceived stress, and norepinephrine in patients with coronary disease: the Heart and Soul Study.
OBJECTIVE
The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established.


METHODS
In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease.


RESULTS
Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0-2.6; the age- and gender-adjusted odds ratio was also 1.6 (95% CI=1.0-2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 mg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0-3.0).


CONCLUSIONS
Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.
Otte
Christian
C
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. otte@uke.uni-hamburg.de
McCaffery
Jeanne
J
Ali
Sadia
S
Whooley
Mary A
MA
D000368:Aged; D002908:Chronic Disease; D002940:Circadian Rhythm / Q000502:physiology; D015897:Comorbidity; D016001:Confidence Intervals; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics* / Q000652:urine; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000652:urine*; D005260:Female; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008297:Male; D009638:Norepinephrine / Q000652:urine*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000175:diagnosis / Q000453:epidemiology*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D009638:Norepinephrine