Pharmacogenetics in major depression: A comprehensive meta-analysis

Niitsu, Tomihisa; Fabbri, Chiara; Bentini, Francesco; Serretti, Alessandro

doi:10.1016/j.pnpbp.2013.05.011

Cited by 178 publications

(149 citation statements)

References 138 publications

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“…Indeed, the rs6265 heterozygous genotype was associated with better treatment outcome as confirmed by a recent meta-analysis (Niitsu et al 2013), although some inconsistent or negative findings were also reported (Fabbri et al 2013a). …”

Section: Genetic Polymorphismsmentioning

confidence: 83%

“…The effect of rs3800373 and rs1360780 on antidepressant response was confirmed in subjects of Caucasian ethnicity by a recent meta-analysis (Niitsu et al 2013). Interestingly, rs1360780 TT genotype showed FKBP5 protein levels that were twice as high as C allele carriers in vitro (Binder et al 2004).…”

Section: Genetic Polymorphismsmentioning

confidence: 92%

“…The study also found that rs878567 (syn-onymous SNP located downstream of the gene) T allele was associated with MDD susceptibility (Kishi et al 2013). The most recent meta-analyses that inves-tigated the role of rs6295 in antidepressant efficacy provided negative findings (Zhao et al 2012;Niitsu et al 2013). Other polymorphisms in the gene were marginally investigated.…”

Section: Genetic Polymorphismsmentioning

confidence: 99%

“…(rs6311 or -1438A/G, rs6313 or 102C/T, rs7997012 and rs7333412) have been investigated within the 5-HT2A gene with several positive but often inconsistent findings (Polesskaya and Sokolov 2002;Lin et al 2009;Fabbri et al 2013b;Niitsu et al 2013;Zhao et al 2014). Interestingly, the region downstream to the first intron of the gene was found to harbour other possibly relevant polymorphisms in the context of anti-depressant response.…”

Section: Genetic Polymorphisms Different Polymorphismsmentioning

confidence: 99%

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Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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Section: Genetic Polymorphismsmentioning

confidence: 83%

Section: Genetic Polymorphismsmentioning

confidence: 92%

Section: Genetic Polymorphismsmentioning

confidence: 99%

Section: Genetic Polymorphisms Different Polymorphismsmentioning

confidence: 99%

See 2 more Smart Citations

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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show abstract

“…Nevertheless, three studies and a meta-analysis [64][65][66][67] demonstrated a significant association between Met allelecarrying genotypes and a higher risk of suicide attempts in depressed patients. Another meta-analysis reported better response to selective serotonin reuptake inhibitors (SSRI) treatment in depressed patients with heterozygous genotypes for Val66Met, compared with homozygous genotypes [68]. A less studied polymorphism (rs11030101) within the BDNF gene has been previously associated with BD [69].…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic factors associated with suicide in mood disorder patients

Antypa¹,

Souery²,

Tomasini³

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.

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ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

Breitenstein

Brückl

Ising

et al. 2015

American J of Med Genetics Pt B

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The efflux pump P-glycoprotein (P-gp), a gene product of the ABCB1 gene, plays a pivotal role in the transfer of various molecules across the blood-brain barrier. P-gp protects the brain by selectively extruding its substrates, including certain antidepressive drugs, thereby limiting their uptake into the brain. Uhr et al. [2008] first showed that ABCB1 variants predicted the remission to antidepressants with P-gp substrate properties in patients suffering from major depression (MD). Other studies investigating the influence of ABCB1 polymorphisms on antidepressant treatment response produced inconclusive results. In this meta-analysis, we systematically summarized 16 pharmacogenetic studies focused on the association of ABCB1 variants and antidepressant treatment outcome in patients with MD (overall n = 2695). We investigated the association of treatment outcome and six ABCB1 single nucleotide polymorphisms (SNPs): rs2032583, rs2235015, rs2235040, rs1045642, rs2032582, rs1128503. We stratified for admission status, ethnicity, and prescription of concomitant medication. SNP rs2032583 showed a nominally significant association across all studies (P = 0.035, SNP was studied in a total of 2,037 patients) and a significant Bonferroni-corrected association among inpatients (P = 1.5 × 10(-05) , n = 485). Also SNP rs2235015 was significantly associated with antidepressant treatment outcome withstanding Bonferroni correction (P = 3.0 × 10(-04) ) among inpatients in a smaller subsample (n = 195). There were no significant associations of the other SNPs tested with antidepressant treatment outcome. Future pharmacogenetic association studies should focus on the role of the ABCB1 SNP rs2032583 in antidepressant outcome prediction.

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Pharmacogenetics in major depression: A comprehensive meta-analysis

Cited by 178 publications

References 138 publications

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Clinical and genetic factors associated with suicide in mood disorder patients

ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

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