Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders

Yw, Yu; Tsai, Shih‐Jen; Tj, Chen; Cai, Lin; Cj, Hong

doi:10.1038/sj.mp.4001141

Cited by 229 publications

(152 citation statements)

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“…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: 73%

“…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: 73%

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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“…Of the MDD patients, 121 had been enrolled in our previous study. 14 An additional 415 normal subjects (male/ female: 195/220; mean age: 41.47 years (s.d. : 16.14)) were enrolled as controls after undergoing a psychiatric interview to rule out psychotic or mood disorders.…”

Section: Methodsmentioning

confidence: 99%

Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

et al. 2008

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Evidence suggests that glycogen synthase kinase-3b (GSK3B) activity is increased significantly in the brain of patients with major depressive disorders (MDD). Inhibition of GSK3B is thought to be a key feature in the therapeutic mechanism of antidepressants. To investigate whether common genetic variants in the GSK3B gene are associated with MDD and the therapeutic response to antidepressants, four polymorphisms (rs334558 (À50 T4C), rs13321783 (IVS7 þ 9227 A4G), rs2319398 (IVS7 þ 11660 G4T) and rs6808874 (IVS11 þ 4251 T4A)) of the GSK3B gene were genotyped in 230 Chinese MDD patients and 415 controls. Among the MDD patients, 168 accepted selective serotonin reuptake inhibitor (SSRI) (fluoxetine or citalopram) antidepressant treatment and therapeutic evaluation for 4 weeks and 117 for 8 weeks. Significant association with MDD was not shown in the alleles and genotypes of single loci or four-locus haplotypes. However, three of the four polymorphisms investigated were significantly associated with 4-week antidepressant therapeutic effect (P ¼ 0.002-0.011). Of the four-locus haplotype analysis, the GSK3B TAGT carriers showed a poorer response to antidepressants in 4-week (Po0.0001) and 8-week (P ¼ 0.015) evaluation compared with other haplotype groups and would quite likely be the nonremitter to 8-week antidepressant treatment (P ¼ 0.006). Our findings show, for the first time, that GSK3B genetic variants play a role in the SSRI antidepressant therapeutic response and support the hypothesis that drugs regulating GSK3B activity may represent a novel treatment strategy for MDD.

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“…These mice show reduced 5-HT tissue concentrations and increased extracellular concentrations of 5-HT in the striatum and probably other structures (for review see Murphy et al 51 ). The l-allele of the 5-HTTLPR polymorphism is associated with better SSRI antidepressive effects than the s-allele 49,52,53 and with faster response to several SSRI's. 54,55 Combined treatment with a 5-HT 1A blocker to prevent negative feedback at the somatodendritic level compensated for the worse antidepressant effect of SSRIs in s/s and s/l genotypes, 56 suggesting higher 5-HT 1A negative feedback in s-allele genotypes.…”

Section: -Ht Transportermentioning

confidence: 97%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders

Cited by 229 publications

References 20 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

Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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