Serotonin receptor 1A −1019C/G variant: Impact on antidepressant pharmacoresponse in melancholic depression?

Baune, Bernhard T.; Hohoff, Christa; Roehrs, Tilmann; Deckert, J.; Arolt, Volker; Domschke, Katharina

doi:10.1016/j.neulet.2008.03.001

Cited by 52 publications

(26 citation statements)

References 27 publications

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“…This hypothesis has been partially confirmed by a series of studies that reported either a better response to SSRIs in patients homozygous for the C allele of 5-HT 1A 83,222,239-242 despite evidence that this variant is not associated with antidepressant response 85,116,243 or restricted solely to the female sex. 244 Baune and colleagues 245 found a better outcome in carriers of the G allele with melancholic depression. A glycine-to-asparatate substitution at amino acid 272 (rs1800042) and its association with antidepressant response has also been explored.…”

Section: -Httlprmentioning

confidence: 98%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

160

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: 98%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

160

103

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“…In an attempt to further extend the present knowledge of the NET and 5-HTT influence on antidepressant treatment response, particular attention was paid to effects potentially specific to gender and melancholic or anxious depression as clinically relevant phenotypes of depression, which have been suggested to be differentially influenced by genetic variants [19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Norepinephrine and Serotonin Transporter Genes: Impact on Treatment Response in Depression

Baffa¹,

Hohoff²,

Baune³

et al. 2010

Neuropsychobiology

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Background/Aims: The norepinephrine transporter (NET) and serotonin transporter (5-HTT) genes constitute promising candidate genes in major depression. Seven polymorphisms in the promoter, intronic and exonic region of the NET gene, as well as serotonin-transporter-linked promoter region (5-HTTLPR) and 5-HTT rs25531 polymorphisms were analyzed with respect to antidepressant treatment response with particular attention to gender effects and subtypes of melancholic or anxious depression. Methods: 252 unrelated Caucasian patients (f = 142; m = 110) with major depression were genotyped for NET and 5-HTT polymorphisms. Genotype effects on Hamilton Depression Rating Scale score changes over 6 weeks of antidepressant treatment were analyzed using analysis of covariance with repeated measures. Results: There was no effect of any of the 7 investigated NET, or the two 5-HTT polymorphisms, on the overall treatment response. An additional –/CT insertion/deletion (ins/del) polymorphism (rs58532686), however, was significantly associated with melancholic depression, with a better response in 12 patients carrying the deletion. Stratification for anxious versus nonanxious depression revealed a significantly detrimental effect of the less active 5-HTTLPR S allele (p = 0.007) and 5-HTTLPR/5-HTT rs25531 haplotypes on treatment response in patients with anxious depression. Conclusion: The present findings do not support a major impact of the NET and 5-HTT genes on antidepressant treatment response in major depression per se. However, there might be an impact of a –/CT ins/del polymorphism in the enhancer domain of the NET gene on treatment response in melancholic depression, which remains to be functionally investigated in future studies. The observed significant influence of the 5-HTT gene variation on antidepressant treatment in anxious depression points to anxious depression as a potential diagnostic entity of its own, requiring specific diagnostic and therapeutic attention.

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“…For example, increased 5-HT platelet reuptake and increased CSF levels of 5-hydroxyindoleacetic acid were found in patients with delusional MDD [34]. The hypothesis is supported also by a previous pharmacogenetic study, which found better antidepressant response in HTR1A rs6295 G allele carriers only when melancholic features were present [21]. …”

Section: Discussionmentioning

confidence: 66%

“…The choice to investigate these two particular subtypes of MDD was due to the need to follow standard DSM-IV criteria to allow easy replication of the results and features of our sample (there were no cases with catatonic features, postpartum onset or atypical features). Moreover, a previous study suggested that antidepressant response in melancholic MDD may be affected by specific genetic variants [21], and the particular clinical features, but also the particular treatment response, of these two subtypes of MDD [22,23,24,25,26] suggest that specific biological factors may be involved.…”

Section: Introductionmentioning

confidence: 99%

TPH1, MAOA, Serotonin Receptor 2A and 2C Genes in Citalopram Response: Possible Effect in Melancholic and Psychotic Depression

Arias

Fabbri²,

Gressier³

et al. 2012

Neuropsychobiology

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Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal. Methods: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD. Results: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F_{(6, 378)} = 2.90; p = 0.009) and melancholic (F_{(6, 381)} = 2.86; p = 0.0097) features. Conclusions: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features.

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Serotonin receptor 1A −1019C/G variant: Impact on antidepressant pharmacoresponse in melancholic depression?

Cited by 52 publications

References 27 publications

Pharmacogenetics of antidepressant response

Pharmacogenetics of antidepressant response

Norepinephrine and Serotonin Transporter Genes: Impact on Treatment Response in Depression

TPH1, MAOA, Serotonin Receptor 2A and 2C Genes in Citalopram Response: Possible Effect in Melancholic and Psychotic Depression

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