Efficacy of Paroxetine in Depression Is Influenced by a Functional Polymorphism Within the Promoter of the Serotonin Transporter Gene

Zanardi, Raffaella; Benedetti, Francesco; Bella, Daniela Di; Catalano, Marco; Smeraldi, Enrico

doi:10.1097/00004714-200002000-00021

Cited by 297 publications

(165 citation statements)

References 11 publications

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“…Indeed some evidence suggest that the association between 5-HTTLPR and treatment response is due to acceleration, more than overall response rate. 24,32,46 The results of our study suggest the period of assessment could be an important factor to evaluate the response rate, while on the other hand the remission rate seemed less influenced by the period of assessment because our results showed no heterogeneity in all remission comparison. This could be due to the fact that remission was evaluated in a longer length of observation: only two studies within 4 weeks.…”

Section: -Httlpr and Ssri Meta-analysismentioning

confidence: 56%

“…This could be due to the fact that remission was evaluated in a longer length of observation: only two studies within 4 weeks. 23,24 Finally, as previously discussed, a causative SNP located nearby the 5-HTTLPR could be the cause for association in the opposite direction in Asians.…”

Section: -Httlpr and Ssri Meta-analysismentioning

confidence: 74%

“…Hardy-Weinberg equilibrium was examined in studies where genotype frequencies were included. 9,[15][16][17][18][19][20][21][22][23][24][25] Given the lack of unequivocal data for 5-HTTLPR genotype pooling, we tested both dominant and recessive hypotheses: l/l versus l/s-s/s and l/l-l/s versus s/s. Outcome was defined with three phenotypes: remission rate, response rate, and response rate within 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

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Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

et al. 2006

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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.

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Section: -Httlpr and Ssri Meta-analysismentioning

confidence: 56%

Section: -Httlpr and Ssri Meta-analysismentioning

confidence: 74%

Section: Methodsmentioning

confidence: 99%

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Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

et al. 2006

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“…Given this insight, the findings of G Â E on population level should not be automatically considered to be due to the functional 5-HTTLPR unless a direct relationship is clearly demonstrated. There is also uncertainty as to the nature of the short allele effect in pharmacogenetics studies of antidepressant response with different studies suggesting recessive, 111,112 dominant 117 or co-dominant effects 118 or even a heterosis effect with worst response in the heterozygotes. 119 Epistasis with the brain-derived neurotrophic factor (BDNF) It is unlikely that the 5-HTTLPR interacts with environmental factors independently of other genes.…”

Section: Serotonin Transporter Gene-environment Interaction R Uher Anmentioning

confidence: 99%

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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“…81 Recently, the SERTPR polymorphism has been associated with the antidepressant response to certain selective serotonin reuptake inhibitors, such as fluvoxamine [82][83][84][85] and paroxetine. 86,87 A possible common mechanism may therefore underlie SSRI and lithium efficacy even if the exact mechanism of action of lithium activity is largely unknown.…”

Section: A Serretti Et Almentioning

confidence: 99%

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

et al. 2004

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We previously reported an association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR) and the prophylactic efficacy of lithium in a sample of 201 Italian subjects affected by Mood disorders. The aim of the present study was to replicate analyses on an independent sample. In total, 83 subjects affected by Bipolar disorder were recruited in the Mood Disorders Clinic of the Eginition Hospital of the Athens University, Medical School Department of Psychiatry. All patients were administered with lithium as prophylactic therapy and they were prospectively observed for at least 3 years. Subjects were typed for their SERTPR variant using polymerase chain reaction techniques. SERTPR variants were associated with lithium outcome among those subjects who had few manic episodes before lithium treatment and, as a trend, among subjects who received a high daily dose of lithium (X1200 mg/die). In both cases, subjects with the l/l variant showed a higher probability to develop an illness episode within 3 years of prophylactic treatment with lithium. The present study confirmed our previous observation of a better response of SERTPR*l/s carriers, but could not confirm a poor efficacy in subjects with the SERTPR*s/s genotype. Notwithstanding the conflicting results, SERTPR variants are a possible liability factor for lithium long-term efficacy in mood disorders. Further studies on independent and large samples are required to determine the reliability and direction of the possible association between SERTPR variants and lithium outcome. INTRODUCTIONLithium is an effective prophylactic agent in mood disorders but not all patients equally respond to lithium therapy. Clinical predictors account for less than half of the variance, 1-8 and there are evidences suggesting that genetic factors play a substantial role in lithium prophylaxis effectiveness. [9][10][11][12][13][14][15][16][17][18][19][20] A large number of studies reported an association between prophylactic lithium response and a family history of bipolar disorder, 10,[12][13][14]17 although not unequivocally confirmed. [21][22][23][24][25] Recently, Grof et al 26 reported that lithium response in a sample of relatives of responder probands was 67% compared to 30% in the comparison group.

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Efficacy of Paroxetine in Depression Is Influenced by a Functional Polymorphism Within the Promoter of the Serotonin Transporter Gene

Cited by 297 publications

References 11 publications

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

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