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Association study of a brain-derived neurotrophic-factor polymorphism and short-term antidepressant response in major depressive disorders.

ABSTRACT: Major depressive disorder (MDD) is one of the most common mental disorders worldwide. Single nucleotide polymorphisms (SNPs) can be used in clinical association studies to determine the contribution of genes to drug efficacy. A common SNP in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is a candidate SNP for influencing antidepressant treatment outcome. In this study, our goal was to determine the relationship between the Val66Met polymorphism in the BDNF gene and the rapid antidepressant response to venlafaxine in a Taiwanese population with MDD. Overall, the BDNF Val66Met polymorphism was found not to be associated with short-term venlafaxine treatment outcome. However, the BDNF Val66Met polymorphism showed a trend to be associated with rapid venlafaxine treatment response in female patients. Future research with independent replication in large sample sizes is needed to confirm the role of the BDNF Val66Met polymorphism identified in this study.

SUBMITTER: Lin E

PROVIDER: S-EPMC3513194 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Association study of a brain-derived neurotrophic-factor polymorphism and short-term antidepressant response in major depressive disorders.

Lin Eugene E Chen Po See PS Huang Lung-Cheng LC Hsu Sen-Yen SY

Pharmacogenomics and personalized medicine 20081021

Major depressive disorder (MDD) is one of the most common mental disorders worldwide. Single nucleotide polymorphisms (SNPs) can be used in clinical association studies to determine the contribution of genes to drug efficacy. A common SNP in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is a candidate SNP for influencing antidepressant treatment outcome. In this study, our goal was to determine the relationship between ...[more]

PMID: 23226029

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Project description:The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known.Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results.Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex.These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features.

Dataset Information

Association study of a brain-derived neurotrophic-factor polymorphism and short-term antidepressant response in major depressive disorders.

Publications

Association study of a brain-derived neurotrophic-factor polymorphism and short-term antidepressant response in major depressive disorders.

Similar Datasets

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