Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression

Anttila, Sami; Huuhka, Kaija; Huuhka, Martti; Rontu, Riikka; Hurme, Mikko; Leìnonen, Esa; Lehtimäki, Terho

doi:10.1007/s00702-007-0705-9

Cited by 89 publications

(52 citation statements)

References 25 publications

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“…Since most suicide attempts by bipolar patients occur during depressive or mixed states [51] , bipolar patients carrying the Met allele may be more vulnerable to depressive symptoms as well as suicidal behavior. This is supported by evidence of an association between the Met allele and geriatric depression [52] , post-stroke depression [53] and the risk of depression, the latter through interactions with the serotonin transporter gene [54][55][56] . Although the Val allele has been associated with susceptibility to bipolar disorder [11,12] , this speculative relationship should be validated by a systematic assessment of the severity of depressive symptoms in bipolar disorder patients.…”

Section: Discussionmentioning

confidence: 49%

Brain-Derived Neurotrophic Factor Val/Met Polymorphism and Bipolar Disorder

Kim¹,

Kim²,

Hong³

et al. 2008

Neuropsychobiology

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Background/Aims: The substitution of valine by methionine in the brain-derived neurotrophic factor (BDNF Val/Met) gene alters the intracellular trafficking and regulated secretion of BDNF. This study tested whether the BDNF Val/Met polymorphism is associated with bipolar disorder in Korean subjects, and whether clinical features vary according to genotype. Methods: The allelic and genotypic distributions of BDNF Val/Met were determined in a population of 169 bipolar patients and 251 normal controls. Between-genotype comparisons of clinical features were performed without a priori knowledge of the genotype of individual patients. Results: Allelic distributions did not differ significantly between bipolar patients and controls (χ² = 0.400, p = 0.821). However, the rate of suicide attempts among the Val/Val (11.3%), Val/Met (28.8%) and Met/Met (38.9%) genotype groups were significantly different (χ² = 9.879, p = 0.007). Relative to patients with the Val/Val genotype, those with the Met/Met genotype had a 4.9-fold higher risk of suicide attempts (95% CI, 1.7–14.7). Conclusions: These findings suggest that BDNF Val/Met is related to the suicidal behavior of bipolar patients, and may have clinical relevance as a biological indicator of bipolar patients at risk of suicide.

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Section: Discussionmentioning

confidence: 49%

Brain-Derived Neurotrophic Factor Val/Met Polymorphism and Bipolar Disorder

Kim¹,

Kim²,

Hong³

et al. 2008

Neuropsychobiology

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“…11,19,21,33,34,36,37,40,42,43 Statistical analysis The meta-analysis examined the allelic association of the Met allele with the risk of MDD relative to the Val allele (OR Met versus Val). Besides this, genotypic ORs were calculated for the heterozygous Val/Met and homozygous Met/Met genotypes separately, with the Val/Val genotype as the reference.…”

Section: Data Extractionmentioning

confidence: 99%

“…Excluded: no MDD phenotype, 8,14,67,68,[85][86][87][88][89][90][91][92][93][94][95][96][97] no case-control design, 22,31,[98][99][100][101][102][103] no adults 104,105 and no Hardy-Weinberg equilibrium (HWE). 106 Included: Caucasian studies, 11,[33][34][35][36][37][38][39][40] Asian studies 19,21,[41][42][43] and gender studies. 11,19,21,[34][35][36][37][38][40]…”

Section: Meta-regression Analysesmentioning

confidence: 99%

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Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

et al. 2008

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Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR MET , 95% CI; 1.27 (1.10-1.47); OR MET/MET , 95% CI; 1.67 (1.19-2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest.

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“…The val66met polymorphism in the BDNF gene has been shown to lead to an increased risk of depression in some, but not all, studies [41][42][43][44] and has been associated with treatment resistant depression in conjunction with the 5HT1A C-(1019)G SNP mentioned previously [45]. MTHFR may also influence serotonin levels.…”

Section: Introductionmentioning

confidence: 99%

Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury

Lanctôt¹,

Rapoport

Chan³

et al. 2010

Brain Injury

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Objectives-To determine which serotonergic system-related single nucleotide polymorphisms (SNPs) predicted variation in treatment response to citalopram in depression following a traumatic brain injury (TBI).Methods-Ninety (50 M/40 F, aged 39.9, SD = 18.0 years) post-TBI patients with a major depressive episode (MDE) were recruited into a 6-week open-label study of citalopram (20 mg/ day). Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value <0.025). Results-MTHFR CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptConclusion-Results suggest that polymorphisms in genes related to the serotonergic system may help predict short-term response to citalopram and tolerability to the medication in patients with MDE following a TBI. KeywordsTraumatic brain injury; serotonin receptors; serotonin transporter; brain derived neurotrophic factor (BDNF); methylenetetrahydrofolate reductase (MTHFR); tryptophan hydroxylase (TPH)

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Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression

Cited by 89 publications

References 25 publications

Brain-Derived Neurotrophic Factor Val/Met Polymorphism and Bipolar Disorder

Brain-Derived Neurotrophic Factor Val/Met Polymorphism and Bipolar Disorder

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury

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