Clinical implications of genetic variation in the serotonin transporter promoter region: a review.
OBJECTIVE
To determine the state of the art in understanding the role of genetic variation in the serotonin transporter (5-HTT) promoter region (5-HTTLPR) in the development of a depressive episode and in its response to treatment.


METHODS
PubMed and Ovid were used to search for articles published prior to December 2007 utilizing the key words serotonin transporter, 5-HTT, 5-HTTLPR, serotonin transporter gene, and SLC6A4.


METHODS
All studies were reviewed, but case reports and small case series were excluded.


METHODS
All relevant articles were read by at least 2 of the coauthors and notes regarding study design, measures, data analysis, and findings were later used to construct the review.


RESULTS
A common genetic variant, the short allele, in which 44 base pairs are missing from the promoter of SLC6A4, is associated with a greater risk for developing a major depressive disorder in patients following exposure to adversity. This association appears to be most important in the early stages of the depressive disorder. Additionally, the likelihood of a positive response to antidepressant treatment may be reduced in these patients in terms of delayed response, greater adverse event load, or, in bipolar patients, mania induction and rapid cycling.


CONCLUSIONS
Selected genetic testing of patients with a recent history of significant adversity may be a reasonable tool that can enlighten treatment options and the course of illness. Ongoing work with the short allele of 5-HTT may also inform clinical guidelines of long-term treatment with antidepressants.
Luddington
Nicole S
NS
Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Kentucky, USA.
Mandadapu
Anitha
A
Husk
Margaret
M
El-Mallakh
Rif S
RS