The influence of Serotonin Transporter Promoter Polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments.
The definition of a genetic liability profile for specific antidepressant treatment will soon be available offering considerable help in early detection of effective therapy in affective disorders. The search for genetic factors predisposing to drug response or side-effects in affective disorders started only in the last few years. The efficacy of antidepressant action was associated with several polymorphisms, located on coding genes of proteins thought to be involved in the different mechanisms of action of antidepressant treatments. Among these, gene variants in sequences of serotonin pathway proteins were candidate, both for the well known evidence of its involvement in the development of depressive symptomathology and for the wide-world use of selective serotonin reuptake inhibitors as first choice treatment of depression. A polymorphism in the promoter region of the serotonin transporter (SERTPR) was independently associated with efficacy for a range of treatments, other polymorphism located on the tryptophan hydroxylase gene, 5-HT2a receptor and G-protein beta 3 showed some association, while other candidate genes were not associated with treatment efficacy. Possible liability genes controlling at least to some extent both acute and long-term treatment were identified, and the further objective is to identify other candidate genes in order to define individualized treatments according to genetic profile in a future. The present paper reviews the pharmacogenetic studies published to date, focusing the attention on the serotonergic pathway.
Serretti
Alessandro
A
Department of Psychiatry, Istituto Scientifico H San Raffaele, Vita-Salute University, Centro San Raffaele del Monte Tabor Foundation, Via Stamira D'Ancona 20, 20127 Milano, Italy. serretti.alessandro@hsr.it
Benedetti
Francesco
F
Zanardi
Raffaella
R
Smeraldi
Enrico
E
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D000928:Antidepressive Agents; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin