News Reader.info

ABSTRACT The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not

consistent across studies. A meta-analysis was performed on 15 studies including data of 1435 subjects. We tested three phenotypes: remission rate, response rate and response rate within 4

weeks using the cochrane review manager. We observed a significant association of the s/s variant of 5-HTTLPR with remission rate (_P_<0.0001) and both s/s and s/l variants with response

rate (_P_=0.0002). Response rate within 4 weeks was associated in both models (_P_=0.003–_P_<0.00001). This effect is quite robust to ethnic differences although a significant

heterogeneity is present in Asian samples. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access

through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink *

Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional

subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS INCIDENCE AND RISK FACTORS OF ANTIDEPRESSANT WITHDRAWAL SYMPTOMS: A META-ANALYSIS AND

SYSTEMATIC REVIEW Article 11 October 2024 GENOME-WIDE ASSOCIATION STUDIES OF ANTIDEPRESSANT CLASS RESPONSE AND TREATMENT-RESISTANT DEPRESSION Article Open access 26 October 2020 ASSOCIATIONS

BETWEEN THE 1438A/G, 102T/C, AND RS7997012G/A POLYMORPHISMS OF HTR2A AND THE SAFETY AND EFFICACY OF ANTIDEPRESSANTS IN DEPRESSION: A META-ANALYSIS Article 23 October 2020 REFERENCES *

Greenberg PE, Stiglin LE, Finkelstein SN, Berndt ER . The economic burden of depression in 1990. _J Clin Psychiatry_ 1993; 54: 405–418. CAS  PubMed  Google Scholar  * Sartorius N . The

economic and social burden of depression. _J Clin Psychiatry_ 2001; 62(Suppl 15): 8–11. PubMed  Google Scholar  * Wittchen H-U, Jacobi F . Size and burden of mental disorders in Europe – a

critical review and appraisal of 27 studies. _Eur Neuropsychopharmacol_ 2005; 15: 357–376. Article  CAS  PubMed  Google Scholar  * Ustun TB . The worldwide burden of depression in the 21st

century. In: Weismann MM (ed). _Treatment of Depression: Bridging the 21st Century_. American Psichiatric Press: Washington, DC, 2001, pp 35–45. Google Scholar  * Fava M, Davidson KG .

Definition and epidemiology of treatment-resistant depression. _Psychiatr Clin North Am_ 1996; 19: 179–200. Article  CAS  PubMed  Google Scholar  * Fava M . Diagnosis and definition of

treatment-resistant depression. _Biol Psychiatry_ 2003; 53: 649–659. Article  PubMed  Google Scholar  * Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D _et al_. Allelic variation

of human serotonin trasporter gene expression. _J Neurochem_ 1996; 66: 2621–2624. Article  CAS  PubMed  Google Scholar  * Serretti A, Calati R, Mandelli L, De Ronchi D . Serotonin

transporter gene variants and behaviour: a comprehensive review. _Current Drug Targets_, in press. * Smeraldi E, Zanardi R, Benedetti F, Dibella D, Perez J, Catalano M . Polymorphism within

the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. _Mol Psychiatry_ 1998; 3: 508–511. Article  CAS  PubMed  Google Scholar  * Serretti A, Artioli P,

Quartesan R . Pharmacogenetics in the treatment of depression: pharmacodynamic studies. _Pharmacogenet Genom_ 2005; 15: 61–67. Article  CAS  Google Scholar  * Smits KM, Smits LJ, Schouten

JS, Stelma FF, Nelemans P, Prins MH . Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic

review. _Mol Psychiatry_ 2004; 9: 433–441. Article  CAS  PubMed  Google Scholar  * Munafo MR, Flint J . Meta-analysis of genetic association studies. _Trends Genet_ 2004; 20: 439–444.

Article  CAS  PubMed  Google Scholar  * Cho HJ, Meira-Lima I, Cordeiro Q, Michelon L, Sham P, Vallada H _et al_. Population-based and family-based studies on the serotonin transporter gene

polymorphisms and bipolar disorder: a systematic review and meta-analysis. _Mol Psychiatry_ 2005; 12: 12. Google Scholar  * Lasky-Su JA, Faraone SV, Glatt SJ, Tsuang MT . Meta-analysis of

the association between two polymorphisms in the serotonin transporter gene and affective disorders. _Am J Med Genet B Neuropsychiatr Genet_ 2005; 133: 110–115. Article  Google Scholar  *

Arias B, Catalan R, Gasto C, Gutierrez B, Fananas L . 5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a

12-weeks follow up study. _J Clin Psychopharmacol_ 2003; 23: 563–567. Article  CAS  PubMed  Google Scholar  * Hong CJ, Chen TJ, Yu YW, Tsai SJ . Response to fluoxetine and serotonin 1A

receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. _Pharmacogenom J_ 2006; 6: 27–33. Article  CAS  Google Scholar  * Joyce PR, Mulder RT, Luty SE, McKenzie JM,

Miller AL, Rogers GR _et al_. Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine

and nortriptyline. _Int J Neuropsychopharmacol_ 2003; 6: 339–346. Article  CAS  PubMed  Google Scholar  * Kato M, Fukuda T, Wakeno M, Fukuda K, Okugawa G, Ikenaga Y _et al_. Effects of the

serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients. _Neuropsychobiol_

2006; 53: 186–195. Article  CAS  Google Scholar  * Kim DK, Lim SW, Lee S, Sohn SE, Kim S, Hahn CG _et al_. Serotonin transporter gene polymorphism and antidepressant response. _Neuroreport_

2000; 11: 215–219. Article  CAS  PubMed  Google Scholar  * Kirchheiner J, Nickchen K, Sasse J, Bauer M, Roots I, Brockmoller J . A 40-basepair VNTR polymorphism in the dopamine transporter

(DAT1) gene and the rapid response to antidepressant treatment. _Pharmacogenom J_ 2006. * Serretti A, Artioli P . The pharmacogenomics of selective serotonin reuptake inhibitors.

_Pharmacogenom J_ 2004; 4: 233–244. Article  CAS  Google Scholar  * Yoshida K, Ito K, Sato K, Takahashi H, Kamata M, Higuchi H _et al_. Influence of the serotonin transporter gene-linked

polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. _Prog Neuropsychopharmacol Biol Psychiatry_ 2002; 26: 383–386. Article  CAS  PubMed  Google

Scholar  * Yu YW, Tsai SJ, Chen TJ, Lin CH, Hong CJ . Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive

disorders. _Mol Psychiatry_ 2002; 7: 1115–1119. Article  CAS  PubMed  Google Scholar  * Zanardi R, Benedetti F, Di Bella D, Catalano M, Smeraldi E . Efficacy of paroxetine in depression is

influenced by a functional polymorphism within the promoter of the serotonin transporter gene. _J Clin Psychopharmacol_ 2000; 20: 105–107. Article  CAS  PubMed  Google Scholar  * Zanardi R,

Serretti A, Rossini D, Franchini L, Cusin C, Lattuada E _et al_. Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional

depression. _Biol Psychiatry_ 2001; 50: 323–330. Article  CAS  PubMed  Google Scholar  * Quitkin FM, Rabkin JG, Ross D, Stewart JW . Identification of true drug response to antidepressants.

Use of pattern analysis. _Arch Gen Psychiatry_ 1984; 41: 782–786. Article  CAS  PubMed  Google Scholar  * Durham LK, Webb SM, Milos PM, Clary CM, Seymour AB . The serotonin transporter

polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. _Psychopharmacology (Berlin)_ 2004; 174: 525–529.

Article  CAS  Google Scholar  * Kraft JB, Slager SL, McGrath PJ, Hamilton SP . Sequence analysis of the serotonin transporter and associations with antidepressant response. _Biol Psychiatry_

2005; 58: 374–381. Article  CAS  PubMed  Google Scholar  * Lee MS, Lee HY, Lee HJ, Ryu SH . Serotonin transporter promoter gene polymorphism and long-term outcome of antidepressant

treatment. _Psychiatr Genet_ 2004; 14: 111–115. Article  PubMed  Google Scholar  * Minov C, Baghai TC, Schule C, Zwanzger P, Schwarz MJ, Zill P _et al_. Serotonin-2A-receptor and

-transporter polymorphisms: lack of association in patients with major depression. _Neurosci Lett_ 2001; 303: 119–122. Article  CAS  PubMed  Google Scholar  * Murphy Jr GM, Hollander SB,

Rodrigues HE, Kremer C, Schatzberg AF . Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major

depression. _Arch Gen Psychiatry_ 2004; 61: 1163–1169. Article  CAS  PubMed  Google Scholar  * Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA _et al_. Allelic variation

in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. _Neuropsychopharmacology_ 2000; 23: 587–590. Article  CAS  PubMed  Google

Scholar  * Rausch JL, Johnson ME, Fei YJ, Li JQ, Shendarkar N, Hobby HM _et al_. Initial conditions of serotonin transporter kinetics and genotype: influence on SSRI treatment trial outcome.

_Biol Psychiatry_ 2002; 51: 723–732. Article  CAS  PubMed  Google Scholar  * Lesch KP . Variation of serotonergic gene expression: neurodevelopment and the complexity of response to

psychopharmacologic drugs. _Eur Neuropsychopharmacol_ 2001; 11: 457–474. Article  CAS  PubMed  Google Scholar  * Hranilovic D, Stefulj J, Schwab S, Borrmann-Hassenbach M, Albus M, Jernej B

_et al_. Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression. _Biol Psychiatry_ 2004; 55: 1090–1094. Article  CAS  PubMed 

Google Scholar  * Greenberg BD, Tolliver TJ, Huang SJ, Li Q, Bengel D, Murphy DL . Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood

platelets. _Am J Med Genet_ 1999; 88: 83–87. Article  CAS  PubMed  Google Scholar  * Javors MA, Seneviratne C, Roache JD, Ait-Daoud N, Bergeson SE, Walss-Bass MC _et al_. Platelet serotonin

uptake and paroxetine binding among allelic genotypes of the serotonin transporter in alcoholics. _Prog Neuropsychopharmacol Biol Psychiatry_ 2005; 29: 7–13. Article  CAS  PubMed  Google

Scholar  * Teshima KM, Przeworski M . Directional positive selection on an allele of arbitrary dominance. _Genetics_ 2006; 172: 713–718. Article  CAS  PubMed  PubMed Central  Google Scholar

  * Williams NM, O'Donovan MC, Owen MJ . Is the dysbindin gene (DTNBP1) a susceptibility gene for schizophrenia? _Schizophr Bull_ 2005; 31: 800–805. Article  PubMed  Google Scholar  *

Allison DB . Transmission-disequilibrium tests for quantitative traits. _Am J Hum Genet_ 1997; 60: 676–690. CAS  PubMed  PubMed Central  Google Scholar  * Peters EJ, Slager SL, McGrath PJ,

Knowles JA, Hamilton SP . Investigation of serotonin-related genes in antidepressant response. _Mol Psychiatry_ 2004; 9: 879–889. Article  CAS  PubMed  Google Scholar  * Hu XZ, Lipsky RH,

Zhu G, Akhtar LA, Taubman J, Greenberg BD _et al_. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. _Am J Hum Genet_ 2006; 78: 815–826.

Article  CAS  PubMed  PubMed Central  Google Scholar  * Nakamura M, Ueno S, Sano A, Tanabe H . The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic

variants. _Mol Psychiatry_ 2000; 5: 32–38. Article  CAS  PubMed  Google Scholar  * Smeraldi E, Serretti A, Artioli P, Lorenzi C, Catalano M . Serotonin transporter gene-linked polymorphic

region: possible pharmacogenetic implications of rare variants. _Psychiatr Genet_ 2006; 16: 153–158. Article  PubMed  Google Scholar  * Kunugi H, Hattori M, Kato T, Tatsumi M, Sakai T,

Sasaki T _et al_. Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. _Mol Psychiatry_ 1997; 2: 457–462. Article  CAS 

PubMed  Google Scholar  * Kato M, Ikenaga Y, Wakeno M, Okugawa G, Nobuhara K, Fukuda T _et al_. Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin

transporter promoter polymorphism. _Int Clin Psychopharmacol_ 2005; 20: 151–156. Article  PubMed  Google Scholar  * Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I _et al_.

Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. _Mol Psychiatry_ 2004; 9: 442–473. Article  CAS  PubMed 

Google Scholar  * Kendler KS . ‘A gene for …’: the nature of gene action in psychiatric disorders. _Am J Psychiatry_ 2005; 162: 1243–1252. Article  PubMed  Google Scholar  Download

references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute of Psychiatry, University of Bologna, Bologna, Italy A Serretti, M Kato & D De Ronchi * Department of Neuropsychiatry,

Kansai Medical University, Osaka, Japan M Kato & T Kinoshita Authors * A Serretti View author publications You can also search for this author inPubMed Google Scholar * M Kato View

author publications You can also search for this author inPubMed Google Scholar * D De Ronchi View author publications You can also search for this author inPubMed Google Scholar * T

Kinoshita View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A Serretti. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Serretti, A., Kato, M., De Ronchi, D. _et al._ Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with

selective serotonin reuptake inhibitor efficacy in depressed patients. _Mol Psychiatry_ 12, 247–257 (2007). https://doi.org/10.1038/sj.mp.4001926 Download citation * Received: 26 July 2006 *

Revised: 31 August 2006 * Accepted: 25 September 2006 * Published: 05 December 2006 * Issue Date: 01 March 2007 * DOI: https://doi.org/10.1038/sj.mp.4001926 SHARE THIS ARTICLE Anyone you

share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the

Springer Nature SharedIt content-sharing initiative KEYWORDS * depression * meta-analysis * 5-HTTLPR * polymorphism * treatment response * SSRI