Dataset Information

Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response.

ABSTRACT:

Context

Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics.

Objective

To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22 kilobases that contained all BDNF exons and their flanking regions.

Design

Case-control study.

Setting

University of California, Los Angeles, and University of Miami.

Participants

Two hundred sixty-four controls and 272 Mexican Americans with major depressive disorder (MDD) from Los Angeles who were assessed by the same bilingual clinical research team.

Main outcome measures

Identification of novel genetic polymorphisms in the BDNF gene and assessment of their frequencies and associations with MDD or antidepressant response.

Results

We identified 83 novel single-nucleotide polymorphisms (SNPs): 30 in untranslated regions, 4 in coding sequences, 37 in introns, and 12 in upstream regions; 3 of 4 rare novel coding SNPs were nonsynonymous. Association analyses of patients with MDD and controls showed that 6 SNPs were associated with MDD (rs12273539, rs11030103, rs6265, rs28722151, rs41282918, and rs11030101) and 2 haplotypes in different blocks (one including Val66, another near exon VIIIh) were significantly associated with MDD. One recently reported 5' untranslated region SNP, rs61888800, was associated with antidepressant response after adjusting for age, sex, medication, and baseline score on the 21-item Hamilton Depression Rating Scale.

Conclusions

Our data support the concept that extensive resequencing of key candidate genes can lead to the discovery of substantial numbers of new variants. Further studies using larger independent samples are needed to confirm the association of the rs61888800 SNP with antidepressant response.

Trial registration

clinicaltrials.gov Identifier: NCT00265291.

SUBMITTER: Licinio J

PROVIDER: S-EPMC4272010 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response.

Licinio Julio J Dong Chuanhui C Wong Ma-Li ML

Archives of general psychiatry 20090501 5

<h4>Context</h4>Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics.<h4>Objective</h4>To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22 kilobases that contained all BDNF exons and their flanking regions.<h4>Design</h4>Case-control study.<h4>Setting</h4>University of Calif ...[more]

PMID: 19414708

Similar Datasets

Project description:Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the "neurotrophin hypothesis of depression" involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD.

Dataset Information

Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response.

Context

Objective

Design

Setting

Participants

Main outcome measures

Results

Conclusions

Trial registration

Publications

Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets