The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder
- 418 Downloads
A common polymorphism (5HTTLPR) within the promoter region of the serotonin transporter gene (LSC6A4) has been shown to influence response time as well as overall response to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder. We hypothesized that a similar effect in response time to sertraline would be observed and that no effect on response time would be seen in a placebo arm.
We tested the hypothesis that subjects homozygous for the long allele at the 5HTTLPR polymorphism would respond more rapidly to sertraline than subjects carrying one or two copies of the short allele.
HAM-D and CGI-I responses to sertraline and placebo were measured weekly in the context of an 8-week, placebo-controlled study in elderly depressed subjects. Genotyping of the 5HTTLPR polymorphism was performed to test for correlations with response at each week in the sertraline and placebo groups (n=206).
Subjects homozygous for the long allele of 5HTTLPR showed a significant increase in response at week 1 and week 2, as assessed by the CGI-I scale compared with subjects carrying one or two copies of the short allele (P=0.01 at both weeks). No significant difference was observed in the placebo group.
These results suggest that genetic variation in the serotonin transporter gene effects the response time to sertraline and provides complementing evidence to previous reports that this polymorphism affects response time to other SSRIs.
Keywords5HTTLPR Genotype Sertraline Placebo Major depressive disorder
The authors would like to extend their thanks to the individuals who donated DNA samples to this study. In addition, we would like to thank Paul Feeney, Jack Ostroff, and Michael Swietek for orchestrating the collection and anonymization of the samples, and Penny Cohen-Dellolio for her efforts in coordinating and monitoring the clinical sites.
- Arias B, Catalan R, Gasto C, Imaz ML, Gutierrez B, Pintor L Fananas L (2001) Genetic variability in the promoter region of the serotonin transporter gene is associated with clinical remission of major depression after long term treatment with cetalopram. World federation of societies of biological psychiatry, vol 2. The World Journal of Biological Psychiatry, Berlin, p 9SGoogle Scholar
- Collier DA, Stober G, Li T, Heils A, Catalano M, Debella D, Arranz MJ, Murray RM, Vallada HP, Bengel D, Muller CR, Roberts GW, Smeraldi E, Kirov G, Sham P, Lesch KP (1996) A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1:453–460PubMedGoogle Scholar
- Guy W (1976) ECDEU assessment manual for psychopharmacology, revised edn. US Department of Health, Education, and Welfare, WashingtonGoogle Scholar
- Pollock BG, Ferrell, RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S, Kirshner MA, Houck PR, Stack JA, Reynolds CF III, Kupfer DJ (2000) Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 23:587–590CrossRefPubMedGoogle Scholar
- Rausch JL, Johnson ME, Fei Y, Li JQ, Shendarkar N, Hobby HM, Ganapathy V, Leibach RH (2002) Initial conditions of serotonin transporter kinetics and genotype: influence of SSRI treatment trial outcome. Biol Psychiatry 51:723–732Google Scholar
- Yoshida K, Ito K, Sato K, Takahashi H, Kamata M, Higuchi H, Shimizu T, Itoh K, Inoue K, Tezuka T, Suzuki T, Ohkubo T, Sugawara K, Otani K (2002) Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 26:383–386Google Scholar