TPH2 polymorphisms may modify clinical picture in treatment-resistant depression

Anttila, Sami; Viikki, Merja; Huuhka, Kaija; Huuhka, Martti; Rontu, Riikka; Lehtimäki, Terho; Leìnonen, Esa

doi:10.1016/j.neulet.2009.08.018

Cited by 30 publications

(26 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rs1386494 of TPH2 has been associated with major depression (Zill et al, 2004a), treatment-resistant depression (Anttila et al, 2009) and suicidal behavior (Zill et al, 2004b). However, we found a negative association between rs1386494 of TPH2 and SCZ in this study.…”

Section: Discussioncontrasting

confidence: 82%

Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population

Tee

Chow²,

Tang³

et al. 2010

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.

show abstract

Section: Discussioncontrasting

confidence: 82%

Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population

Tee

Chow²,

Tang³

et al. 2010

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…[ 3 ]] not in terms of citalopram response, but in terms of level 2 and 3 (i.e., next-step) treatment outcomes. Of the four genes studied, onethe potassium channel gene KCNK2, or TREK1 -was signifi cantly associated with failure to respond to two or more treatments and three or more treatments in STAR*D. Notably, this effect was not apparent when citalopram responders and nonresponders were contrasted, suggesting the potential utility of studying more extreme phenotypes.…”

Section: Association Studies Of Trdmentioning

confidence: 99%

“…Association was reported for a SNP in vascular endothelial growth factor (VEGF) -VEGF2578 [ 38 ] as well as one in tryptophan hydroxylase 1 (TPH1) [ 41 ]. (As noted below, the same authors also investigated other candidates including the serotonin 2A receptor (HTR2A) [ 39 ], tryptophan hydroxylase 2 (TPH2) [ 3 ], and multiple other genes (ACE, RGS4, GNB3).…”

Section: Association Studies Of Trdmentioning

confidence: 99%

“…In one report, one SNP (rs11030101) in brain-derived neurotrophic factor (BDNF) was associated with response [ 40 ]. However, this result must be interpreted in the context of numerous negative associations drawn from the same cohort, including TPH2 [ 3 ], angiotensin converting enzyme (ACE) [ 34 ], regulator of G protein signaling 4 (RGS4) [ 18 ], and apolipoprotein E (APOE) [ 19 ]. Another study failed to identify main effects for SNPs in HTR2A previously associated with antidepressant response, although SNP-by-sex effects were suggested [ 39 ].…”

Section: Treatment Outcomes In Trd Cohortsmentioning

confidence: 99%

“…This palette of enzymes is responsible for hepatic phase I metabolism of many psychotropic medications [see Chap. [ 3 ]]. …”

Section: Clinical Statusmentioning

confidence: 99%

See 2 more Smart Citations

Genomic Studies of Treatment Resistance in Major Depressive Disorder

Perlis

2016

Genetic Influences on Response to Drug Treatment for Major Psychiatric Disorders

View full text Add to dashboard Cite

Treatment-resistant depression describes the subset of individuals with major depressive disorder who do not reach symptomatic remission despite multiple adequate treatment trials. While treatment resistance has a substantial impact on functioning, quality of life, and healthcare costs, little is known about the underlying neurobiology. While at least some treatment-resistant depression (TRD) risk is likely to be heritable, based primarily on evidence from antidepressant pharmacogenomics, studies to date have failed to reliably identify rare or common genetic variation associated with this phenotype. Challenges in the study of TRD include misclassifi cation arising from medication intolerance or inadequate treatment trials, the heterogeneity of the concept itself, and most notably the absence of well-characterized cohorts with DNA available for study. New strategies to identify large cohorts from biobanks or disease registries and efforts to meta-analyze multiple cohorts may facilitate the identifi cation of risk variants. In addition, further studies to understand the potential utility of pharmacogenomic testing among individuals with TRD or to stratify risk for TRD are needed. Background and MotivationAround 1/3 of individuals who receive initial antidepressant treatment for major depressive disorder will not reach symptomatic remission. A subset of these, perhaps approaching 50 %, will not remit despite additional antidepressant treatment [ 31 ]. Such nonremission in the face of adequate antidepressant trials is referred to as treatment-resistant depression [ 9 ], a concept fi rst characterized more than 40

show abstract