Effect of 5‐HT1A gene polymorphisms on antidepressant response in major depressive disorder

Kato, Masaki; Fukuda, Tsuyoshi; Wakeno, Masataka; Okugawa, Gaku; Takekita, Yoshiteru; Watanabe, Syunsuke; Yamashita, Megumi; Hosoi, Yuka; Azuma, Junichi; Kinoshita, Toshihiko; Serretti, Alessandro

doi:10.1002/ajmg.b.30783

Cited by 100 publications

(56 citation statements)

References 39 publications

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“…Carriers of the asparatate allele seemed to have a greater reduction in depressive symptomatology compared with glycine homozygotes, 246 although this finding was not confirmed in subsequent studies. 243,244 Recently, Kato and colleagues 239 reported several other polymorphisms within this gene associated with better response (e.g., rs10042486 C/C and rs1364043 T/T). Table 7 lists relevant studies on this topic.…”

Section: -Httlprmentioning

confidence: 99%

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Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

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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: -Httlprmentioning

confidence: 99%

“…13. 267 It is a G protein-coupled receptor that stimulates adenylyl cyclase via G coupling, together with receptors Porcelli et al 239 …”

Section: Serotoninmentioning

confidence: 99%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

Self Cite

161

103

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“…One of the widely discussed causes is a polymorphism of 5-HT1A receptor-encoding gene, Htr1a [32,33]. A mechanism by which SSRI exert their antidepressant effects involves the desensitization of presynaptic 5-HT1A receptors due to the rise of the extracellular 5-HT [34][35][36][37].…”

Section: Fluoxetine Monotherapymentioning

confidence: 99%

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

et al. 2012

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Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitaryadrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamopituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.

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“…We contacted the corresponding authors with regard to the genotype data in these studies. They and Kato et al 20 informed us that there were no genotyping errors. (3) The overall sample size included in the meta-analysis was relatively small (1658 patients and 2046 control subjects).…”

Section: Discussionmentioning

confidence: 94%

Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis

et al. 2009

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Several genetic studies have shown an association between the 5-HT1A receptor gene (HTR1A) and major depressive disorder (MDD); however, results have been rather inconsistent. Moreover, to our knowledge, no association study on HTR1A and MDD in the Japanese population has been reported. Therefore, to evaluate the association between HTR1A and MDD, we conducted a case-control study of Japanese population samples with two single-nucleotide polymorphisms (SNPs), including rs6295 (C-1019G) in HTR1A. In addition, we conducted a meta-analysis of rs6295, which has been examined in other papers. Using one functional SNP (rs6295) and one tagging SNP (rs878567) selected with the HapMap database, we conducted a genetic association analysis of case-control samples (331 patients with MDD and 804 controls) in the Japanese population. Seven population-based association studies, including this study, met our criteria for the meta-analysis of rs6295. We found an association between rs878567 and Japanese MDD patients in the allele-wise analysis, but the significance of this association did not remain after Bonferroni's correction. We also did not detect any association between HTR1A and MDD in the allele/ genotype-wise or haplotype-wise analysis. On the other hand, we detected an association between rs6295 and MDD in the metaanalysis (P(Z)¼0.0327). In an explorative analysis, rs6295 was associated with Asian MDD patients after correction for multiple testing (P(Z)¼0.0176), but not with Caucasian MDD patients (P(Z)¼0.138). Our results suggest that HTR1A may not have a role in the pathophysiology of Japanese MDD patients. On the other hand, according to the meta-analysis, HTR1A was associated with MDD patients, especially in the Asian population. Keywords: case-control study; functional SNP; major depressive disorder (MDD); meta-analysis; serotonin 1A receptor gene (HTR1A); tagging SNP INTRODUCTION Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for major depressive disorder (MDD). The evidence for such an association is discussed in more detail in reviews. 1,2 Several genetic studies have shown an association between the serotonin 1A (5-HT1A) receptor gene (HTR1A) and MDD; however, results have been rather inconsistent. A recent meta-analysis showed no association between HTR1A and MDD. 3 However, two very recent studies reported that rs6295 (C-1019G) in the promoter region of HTR1A, which regulates HTR1A transcription, 4,5 was associated with MDD in the Chinese population. 6,7 Moreover, to our knowledge, no association study of HTR1A and MDD in the Japanese population has been reported. Therefore, we examined the association between HTR1A and MDD in the Japanese, using the recently recommended strategy of 'genebased' association analysis. 8 Moreover, we conducted an updated

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Effect of 5‐HT1A gene polymorphisms on antidepressant response in major depressive disorder

Cited by 100 publications

References 39 publications

Pharmacogenetics of antidepressant response

Pharmacogenetics of antidepressant response

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis

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