Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder

Chen, Hong; Tj, Chen; Yu, Younger W.‐Y.; Tsai, Shih‐Jen

doi:10.1038/sj.tpj.6500340

Cited by 169 publications

(107 citation statements)

References 38 publications

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“…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%

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: Methodsmentioning

confidence: 99%

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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“…Although not covering the locus systematically, several previous studies have provided suggestive evidence for an involvement of other HTR2A variants in antidepressant outcome (Minov et al, 2001;Cusin et al, 2002;Peters et al, 2004;Choi et al, 2005;Hong et al, 2006;Kato et al, 2006;McMahon et al, 2006;Paddock et al, 2007;Perlis et al, 2009). Post-mortem (McKeith et al, 1987Lopez-Figueroa et al, 2004) and positron emission tomography (PET) (Yates et al, 1990;Yatham et al, 2000;Mintun et al, 2004) studies have reported both increased and decreased HTR2A receptor number and binding in different brain regions of depressed individuals.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in GRIK4, HTR2A, and FKBP5 Show Interactive Effects in Predicting Remission to Antidepressant Treatment

Horstmann

Lucae

Menke

et al. 2009

Neuropsychopharmacol

171

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Single-nucleotide polymorphisms (SNPs) in the FKBP5, GRIK4, and HTR2A genes have been shown to be associated with response to citalopram treatment in the STAR*D sample, but only associations with FKBP5 have so far been tested in the Munich Antidepressant Response Signature (MARS) project. Response and remission of depressive symptoms after 5 weeks of antidepressant treatment were tested against 82 GRIK4 and 37 HTR2A SNPs. Association analysis was conducted in about 300 depressed patients from the MARS project, 10% of whom had bipolar disorder. The most predictive SNPs from these two genes and rs1360780 in FKBP5 were then genotyped in a total of 387 German depressed in-patients to analyze potential additive and interactive effects of these variants. We could not replicate previous findings of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study in our sample. Although not statistically significant, the effect for the best GRIK4 SNP of STAR*D (rs1954787, p ¼ 0.076, p corrected ¼ 0.98) seemed to be in the same direction. On the other hand, the nominally significant association with the top HTR2A SNPs of STAR*D (rs7997012, allelic, p ¼ 0.043, p corrected ¼ 0.62) was with the opposite risk allele. The GRIK4 SNP (rs12800734, genotypic, p ¼ 0.0019, p corrected ¼ 0.12) and the HTR2A SNP (rs17288723, genotypic, p ¼ 0.0011, p corrected ¼ 0.02), which showed the strongest association with remission in our sample, had not been reported previously. Associations across all genetic markers within the GRIK4 (genotypic, p ¼ 0.022) or HTR2A (genotypic, p ¼ 0.012) locus using the Fisher's product method (FPM) were also significant. In all 374 patients, the best predictive model included a main effect for GRIK4 rs12800734 and two significant interactions between GRIK4 rs12800734 and FKBP5 rs1360780, and GRIK4 rs12800734 and HTR2A rs17288723. This three SNP model explained 13.1% of the variance for remission after 5 weeks (p ¼ 0.00051 for the model). Analyzing a sub-sample of 194 patients, plasma ACTH (p ¼ 0.002) and cortisol (p ¼ 0.021) responses of rs12800734 GG (GRIK4) carriers, who also showed favorable treatment response, were significantly lower in the second combined dexamethasone (dex)/corticotrophin-releasing hormone (CRH) test before discharge compared with the other two genotype groups. Despite large differences in ethnicity and design compared with the STAR*D study, our results from the MARS study further support both independent and interactive involvement of GRIK4, HTR2A and FKBP5 in antidepressant treatment response.

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“…6 In contrast to these findings, the majority of previous studies investigating the inheritance of 5-HTTLPR genotype on antidepressant efficacy have found the short allele to be associated with reduced antidepressant response. [7][8][9][10][11][12][13][14][15][16] This may be explained by a number of variables that differ between the studies. First, variation in the criteria used to measure response has differed between studies, with a reduction of 50% or more from baseline Hamilton Depression Rating Scale (HAMD) scores used in certain studies, 4,5,7,13,[15][16][17] but an HAMD score of 8 or less was used to determine response in other studies.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy

et al. 2008

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The majority of antidepressant drugs act by increasing synaptic serotonin levels in the brain. Genetic variation in serotonin-related genes may therefore influence antidepressant efficacy. In this study, nine polymorphisms in four serotonin receptor genes (HTR1B, HTR2A, HTR5A and HTR6) and the serotonin transporter gene (SLC6A4) were analysed to investigate their influence on antidepressant response in a well-characterized unipolar depressive population (n ¼ 166) following a protocolized treatment regimen. 5-HTTLPR short-allele homozygotes were significantly associated with both remission (odds ratios (OR) ¼ 4.00, P ¼ 0.04) and response (OR ¼ 5.06, P ¼ 0.02) following second switch treatment, with a similar trend observed following initial treatment and paroxetine therapy. Following initial treatment, unipolar patients homozygous for the SLC6A4 intron 2 repeat polymorphism were significantly associated with lack of remission (OR ¼ 0.38, P ¼ 0.02) and lack of response (OR ¼ 0.42, P ¼ 0.01). Additionally, the HTR2A C 1354 T polymorphism showed an association with remission (OR ¼ 7.50, P ¼ 0.002) and response (OR ¼ 5.25, P ¼ 0.01) following paroxetine therapy. These results suggest that genetically determined variation in serotonin receptor genes makes a significant contribution to the efficacy of commonly prescribed antidepressant drugs.

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Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder

Cited by 169 publications

References 38 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

Polymorphisms in GRIK4, HTR2A, and FKBP5 Show Interactive Effects in Predicting Remission to Antidepressant Treatment

Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy

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