VIENNA – Patients with coronary heart disease who carry the short allele of the serotonin transporter gene have significantly higher rates of major depression and perceived stress than do those who are homozygous for the long allele, Dr. Christian Otte said at the annual congress of the European College of Neuropsychopharmacology.
Moreover, patients with coronary heart disease (CHD) who carry the s (or short) allele of a functional polymorphism in the promoter region of the serotonin transporter gene also have higher 24-hour norepinephrine excretion than do those who have two long alleles (the l/l genotype), according to data from the prospective Heart and Soul Study.
“Since both depression and higher norepinephrine values have been associated with worse cardiac outcome, this might be a mechanism by which carriers of the short allele of the serotonin transporter gene might be at greater risk to suffer from cardiac events,” explained Dr. Otte, a psychiatrist at University Hospital Hamburg-Eppendorf (Germany).
The Heart and Soul Study is an ongoing prospective cohort study based at the University of California, San Francisco, and involving 1,024 patients with CHD. The aim of the study is to shed new light on the association between depression and cardiovascular events. For purposes of the genetic study of serotonin transporter gene polymorphism, Dr. Otte restricted the analysis to the 557 whites, the largest racial group in the study. Of this group, 17% were homozygous for the s/s genotype, 52% were s/l, and 31% were l/l.
The prevalence of current major depression as assessed by the Computerized Diagnostic Interview Schedule was 25% among participants carrying an s allele, a significantly higher rate than the 17% in l/l subjects. After statistical adjustment for age and gender, CHD patients with an s allele for the serotonin transporter gene had a 60% increased rate of major depression. They also were 60% more likely to score in the moderate to high range for perceived stress, as reflected in a score greater than 5 on the Perceived Stress Scale.
Moreover, s allele carriers had a mean 24-hour norepinephrine excretion of 55.6 mg/day, compared with 50.2 mg/day in l/l patients, and they were 70% more likely to fall within the top quartile for 24-hour norepinephrine.
Dr. Otte said his research was inspired by a “classic” study of conducted by investigators at King's College London, who demonstrated that carriers of one or two copies of the s allele who experienced stressful life events were much more likely to develop depression than were l/l individuals with a comparable degree of life stress (Science 2003;301:386–9).
The Heart and Soul Study investigators reasoned that a chronic debilitating medical illness such as CHD might operate as an ongoing major stressor that would permit them to learn whether the s allele is related to depression, an extremely common CHD comorbidity.
The study is supported by the Department of Veterans Affairs, the Robert Wood Johnson Foundation, the American Federation for Aging Research, the Ischemia Research and Education Foundation, and NARSAD: The Mental Health Research Association.
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