Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients

Yoshida, Keizo; Ito, Kenichi; Sato, Kazuhiro; Takahashi, Hitoshi; Kamata, Mitsuhiro; Higuchi, Hisashi; Shimizu, Tetsuo; Itoh, Ken; Inoue, Ken‐ichiro; Tezuka, Takehiko; Suzuki, Toshio; Ohkubo, Tadashi; Sugawara, Kazunobu; Otani, Koichi

doi:10.1016/s0278-5846(01)00287-1

Cited by 207 publications

(142 citation statements)

References 17 publications

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“…First, the most obvious limitation of this study is that the duration for fluoxetine evaluation was 4 weeks, although there have also been some studies which used 4 weeks as the time point in short-term antidepressant treatment response evaluation (eg Minov et al, 2001;Serretti et al, 2001;Yoshida et al, 2002a). This is the minimal time expected for a treatment response and we may only identify rapid responders, not all responders, to fluoxetine treatment.…”

Section: Discussionmentioning

confidence: 99%

Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response

Yu¹,

Tsai

Hong

et al. 2005

Neuropsychopharmacol

161

121

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Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of biogenic amines, may be implicated in the pathogenesis of major depressive disorder (MDD) and be related to the therapeutic effects of antidepressants. To elucidate a genetic predisposition of MDD, we studied a variable-number-tandem-repeat (VNTR) polymorphism in the promoter region of the MAOA gene in a Chinese population of 230 MDD patients and 217 controls. We also examined the association of this polymorphism and antidepressant therapeutic response in the MDD patients who underwent a 4-week fluoxetine treatment. Our results showed a significantly increased frequency of 4-repeat (4R) allele in MDD patients, especially in the female population. Furthermore, MDD female patients who were 3R homozygotes had a significantly better response to 4-week fluoxetine treatment when compared to 4R carriers (p ¼ 0.024), but there was a nonsignificant difference found in male patients (p ¼ 0.081). Since the 4R allele transcribed 2-10 times more efficiently than those with 3R allele, our findings suggest that the MAOA-uVNTR may be involved in the pathogenesis of MDD and the antidepressant therapeutic mechanisms in Chinese population, and that there may be a gender effect in this association.

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Section: Discussionmentioning

confidence: 99%

Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response

Yu¹,

Tsai

Hong

et al. 2005

Neuropsychopharmacol

161

121

View full text Add to dashboard Cite

show abstract

“…Again, heterozygote frequencies were higher in non-responders (47 vs 31%) which further suggests a recessive allele effect. 5 Both these studies were, however, carried out in Oriental populations where the frequencies of the 5-HTTLPR genotypes differ from Caucasian populations, with the short/short genotype frequency approximately 25% in Caucasian populations but 57% in Asian populations. 2 However, a recent study using a mixed American population (78% Caucasians, 6% African American, 7% Hispanic, 5% Asian and 3% other) also found the short allele to be associated with response to fluoxetine.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy

et al. 2008

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The majority of antidepressant drugs act by increasing synaptic serotonin levels in the brain. Genetic variation in serotonin-related genes may therefore influence antidepressant efficacy. In this study, nine polymorphisms in four serotonin receptor genes (HTR1B, HTR2A, HTR5A and HTR6) and the serotonin transporter gene (SLC6A4) were analysed to investigate their influence on antidepressant response in a well-characterized unipolar depressive population (n ¼ 166) following a protocolized treatment regimen. 5-HTTLPR short-allele homozygotes were significantly associated with both remission (odds ratios (OR) ¼ 4.00, P ¼ 0.04) and response (OR ¼ 5.06, P ¼ 0.02) following second switch treatment, with a similar trend observed following initial treatment and paroxetine therapy. Following initial treatment, unipolar patients homozygous for the SLC6A4 intron 2 repeat polymorphism were significantly associated with lack of remission (OR ¼ 0.38, P ¼ 0.02) and lack of response (OR ¼ 0.42, P ¼ 0.01). Additionally, the HTR2A C 1354 T polymorphism showed an association with remission (OR ¼ 7.50, P ¼ 0.002) and response (OR ¼ 5.25, P ¼ 0.01) following paroxetine therapy. These results suggest that genetically determined variation in serotonin receptor genes makes a significant contribution to the efficacy of commonly prescribed antidepressant drugs.

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“…The most consistent findings have been of associations between antidepressant treatment response with the insert/delete polymorphism of the upstream regulatory region of the serotonin transporter gene. [39][40][41][42][43][44] Other genes shown to be associated with antidepressant treatment response include tryptophan hydroxylase 45,46 and the serotonin 2 A receptor. 47 Antidepressants act on monoaminergic systems with pharmacological effects that are rapid and biochemically evident within hours of initial drug administration.…”

Section: Discussionmentioning

confidence: 99%

Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans

et al. 2004

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There are well-replicated, independent lines of evidence supporting a role for corticotropinreleasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CRHR1 genotypes with the phenotype of antidepressant treatment response in 80 depressed Mexican-Americans in Los Angeles who completed a prospective randomized, placebo lead-in, double-blind treatment of fluoxetine or desipramine, with active treatment for 8 weeks. Subjects were included into the study if they had a diagnosis of depression without other confounding medical or psychiatric diagnoses or treatments. All patients were followed weekly and assessed for changes in the Hamilton rating scales for anxiety (HAM-A) and depression (HAM-D). Inclusion criteria in the study included a HAM-D of 18 or higher. Because CRHR1 affects both depression and anxiety. Patients were classified into a high-anxiety (HA) group if their HAM-A score was 18 or higher and in a low-anxiety (LA) group if their HAM-A score was less than 18. Utilizing the haplotype-tag single-nucleotide polymorphisms rs1876828, rs242939 and rs242941, we tested for haplotypic association between CRHR1 and 8-week response to daily antidepressant treatment. In the HA group (n ¼ 54), homozygosity for the GAG haplotype was associated with a relative 70% greater reduction in HAM-A scores compared to heterozygous (63.174.5 vs 37.176.9%, respectively, P ¼ 0.002). For HAM-D, GAG haplotype homozygosity was associated with a 31% greater reduction in scores after treatment compared to heterozygous (67.374.3 vs 51.276.0%, respectively, P ¼ 0.03). In those with loweranxiety levels at screening, there were no associations between CRHR1 genotype and percent change in HAM-A or HAM-D. These findings of increased response to antidepressants in highly anxious patients homozygous for the GAG haplotype of CRHR1 need to be independently validated and replicated. Such work would support the hypotheses that response to antidepressant treatment is heterogeneous and that the CRHR1 gene and possibly other genes in stress-inflammatory pathways are involved in response to antidepressant treatment. These findings also suggest that variations in the CRHR1 gene may affect response to CRHR1 agonists or antagonists. All data are deposited in www.pharmgkb. Keywords: corticotropin-releasing hormone; corticotropin-releasing hormone receptor; MexicanAmerican; Hispanic; depression; anxiety Major depression is a common and complex disorder of gene-environment interactions. 1 The specific genetic substrates and precipitating environmental factors have not yet been elucidated. The disorder affects 10% of males and 20% of females and has a point prevalence of 3%. Its cost to the US economy exceeds 100 billion dollars per year. 2 Over 20 drugs are approved by the US Food and Drug Administration for treatment of depression, each one with efficacy of approximately 60%. Various subgroups ...

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Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients

Cited by 207 publications

References 17 publications

Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response

Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response

Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy

Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans

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