Primary care companion to the Journal of clinical psychiatry · 2009
Clinical implications of genetic variation in the serotonin transporter promoter region: a review.
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Luddington Nicole S, Mandadapu Anitha, Husk Margaret, El-Mallakh Rif S
Аннотация
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.
DATA SOURCES: 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.
STUDY SELECTION: All studies were reviewed, but case reports and small case series were excluded.
DATA EXTRACTION: 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.
DATA SYNTHESIS: 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.
DATA SOURCES: 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.
STUDY SELECTION: All studies were reviewed, but case reports and small case series were excluded.
DATA EXTRACTION: 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.
DATA SYNTHESIS: 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.