Polymorphism of the serotonin transporter: implications for the use of selective serotonin reuptake inhibitors.
Selective serotonin reuptake inhibitors (SSRIs) are used to treat a number of psychiatric disorders related to mood and anxiety, and variations in the serotonin transporter (5-HTT) gene may be involved in a number of these. A polymorphic site in the promoter region is associated with differences in 5-HTT gene expression. Studies suggest that the short allele of the 5-HTT promoter (5-HTTPR) site can adversely influence the antidepressant response to SSRIs, and is associated with anxiety-related traits, depression, and impulsive disorders such as alcohol abuse. Several studies do not replicate these findings; potential confounding factors include age, gender, and population stratification. Other 5-HTT polymorphisms also exist. For example, individuals with the short allele of a variable number of tandem repeats (VNTR) polymorphism, located in the second intron, may have reduced responsiveness to SSRIs, and the STin2.12 allele at this site has been associated with bipolar disorder. Findings both supporting and inconsistent with these conclusions are reviewed. The clinical effects of the polymorphisms may be associated with effects on platelets, neural 5-HTT levels, and indices of serotonergic function.
Lotrich
F E
FE
Department of Psychiatry, Western Psychiatric Institute and Clinics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Pollock
B G
BG
Ferrell
R E
RE
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics*; D026901:Membrane Transport Proteins; D001523:Mental Disorders / Q000188:drug therapy / Q000235:genetics; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human