Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response

Min, Wenjiao; Li, Tao; Ma, Xiaoyan; Li, Zhengyu; Yu, Tao; Gao, Dong; Zhang, Bo; Yun, Yang; Sun, Xiaochuan

doi:10.1007/s00213-009-1550-3

Cited by 69 publications

(39 citation statements)

References 48 publications

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“…It was reported that the STin2 polymorphism can play a role as a risk factor in MDD [198][199][200] and suicidal behaviour, 201,202 creating a synergistic effect with 5-HTTLPR. 203 The STin2 polymorphism seems to also affect antidepressant response, as reported by different authors, 85,175,182,191 and it was proposed that a STin2 10/12 genotype (where 10/12 indicates the number of repeats in the 2 alleles) may be associated with a poorer antidepressant effect, especially in Asian populations. 204 Some studies were not able to replicate these findings.…”

Section: Comtmentioning

confidence: 88%

“…[176][177][178][179][180] On the other hand, studies involving Asian populations usually report conflicting results: some studies reported that the short 5-HTTLPR allele was associated with better outcomes, [181][182][183][184] some found no effect of 5-HTTLPR genotype on treatment efficacy 121,185,186 and some reported that the long 5-HTTLPR allele was associated with better outcomes. 83,[187][188][189][190][191] Interestingly, Lotrich and colleagues 192 recently reported that paroxetine blood concentration was positively associated with HAM-D response in a sample of elderly patients, but this association was found to be significant only in carriers of the short allele. In contrast, when augmentation strategies have been investigated, the short allele has been associated with a better response in patients prescribed pindolol or lithium.…”

Section: Comtmentioning

confidence: 99%

“…191 In a genome-wide association study, rs36029 and rs1532701 showed nominally significant associations with response to nortriptyline, but neither of them survived after gene-wide or hypothesis-wide correction.…”

Section: -Httlprmentioning

confidence: 99%

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Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

154

103

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87Personalized medicine -the adaptation of therapies based on an individual's genetic and molecular profile -is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

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Section: Comtmentioning

confidence: 88%

Section: Comtmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

154

103

View full text Add to dashboard Cite

show abstract

“…For instance, polymorphisms in the SLC6A4 gene were associated with antidepressant response or remission [28,68,76,81,88,91]. Similar SLC6A4 variants have shown an association with lithium treatment outcomes in patients with BPD [75,102].…”

Section: Lithium Treatment For Bipolar Disordermentioning

confidence: 97%

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry. So far, the progress of uncovering single nucleotide polymorphisms (SNPs) underpinning treatment efficacy in mood disorders (e.g., SNPs associated with selective serotonin re-uptake inhibitors or lithium treatment response in patients with bipolar disorder and major depressive disorder) are encouraging, but not adequate. Genetic studies have pointed to a number of SNPs located at candidate genes that possibly influence response to; (a) antidepressants COMT, HTR2A, HTR1A, CNR1, SLC6A4, NPY, MAOA, IL1B, GRIK4, BDNF, GNB3, FKBP5, CYP2D6, CYP2C19, and ABCB1 and (b) mood stabilizers (lithium) 5-HTT, TPH, DRD1, FYN, INPP1, CREB1, BDNF, GSK3β, ARNTL, TIM, DPB, NR3C1, BCR, XBP1, and CACNG2. We suggest three alternative and complementary strategies to implement knowledge gained from pharmacogenomic studies. The first strategy can be to implement diagnostic, therapeutic, or prognostic genetic testing based on candidate genes or gene products. The second alternative is an integrative analysis (systems genomics approach) to combine omics data obtained from the different pillars of omics investigation, including genomics, epigenomes, proteomics, metabolomics and microbiomes. The main goal of system genomics is an identification and understanding of biological pathways, networks, and modules underlying drug-response. The third strategy aims to the development of multivariable diagnostic or prognostic algorithms (tools) combining individual's genomic information (polygenic score) with other predictors (e.g., omics pillars, neuroimaging, and clinical characteristics) to finally predict therapeutic outcomes. An integration of molecular science with that of traditional clinical practice is the way forward to drug discoveries and novel therapeutic approaches and to characterize psychiatric disorders leading to a better predictive, preventive, and personalized medicine (PPPM) in psychiatry. With future advances in the omics technology and methodological developments for data integration, the goal of PPPM in psychiatry is promising.

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“…Another polymorphism influencing SERT expression, described as 17bp VNTR polymorphism, was identified within intron 2 (STin2) [80]. Several studies reported an influence of STin2 on response to ADs, but other investigations were not able to repeat these findings [81][82][83][84][85]. Moreover, it was proposed that STin2 10/12 genotype may be associated with poorer antidepressant effect, especially in Asian populations [86].…”

Section: Serotonin Transporter (Slc6a4)mentioning

confidence: 99%

Pharmacogenetics of antidepressant drugs: An update

Crisafulli¹,

Drago²,

Calabrò³

et al. 2014

Hosp Pharm Int Multi J

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SUMMARYPharmacological treatment of depressive disorders is characterized by poor predictability of individual response. In recent years, the increasing evidence has demonstrated that genetic factors play a critical role in determining the differences in treatment outcome to antidepressant drugs. A number of pharmacogenetic studies on antidepressant drugs has been conducted, and genetic variations at level of drug metabolizing enzymes, drug transporters and drug targets, possibly influencing the clinical response, have been identified. Pharmacogenetics may hopefully provide the basis for individualized pharmacotherapy of depressive disorders in order to maximize the probability of a favorable response and minimize the risk of adverse drug reactions. In this article, the major findings related to the pharmacogenetics of genes involved in the pharmacokinetics and pharmacodynamics of antidepressant drugs are critically reviewed.

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Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response

Cited by 69 publications

References 48 publications

Pharmacogenetics of antidepressant response

Pharmacogenetics of antidepressant response

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

Pharmacogenetics of antidepressant drugs: An update

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