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Impact of the BDNF Val66Met Polymorphism on Regional Brain Gray Matter Volumes: Relevance to the Stress Response.

ABSTRACT: OBJECTIVE:Genetic imaging is used to investigate the mechanism by which genetic variants influence brain structure. In a previous study, a structural change of the dorsolateral prefrontal cortex was associated with symptom modulation in post-traumatic stress disorder patients. This study examined the effect of a polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF) on regional gray matter (GM) volumes and the correlations between the dorsolateral prefrontal GM volume and the stress level in healthy volunteers. METHODS:Sixty-one volunteers underwent genotyping for the BDNF Val66Met single nucleotide polymorphism (SNP) and completed the Stress Response Inventory (SRI). Magnetic resonance images were also acquired, and the effect of each subject's BDNF genotype and SRI subscore on his or her dorsolateral prefrontal GM volume was evaluated. RESULTS:The Val/Val homozygotes had significantly larger GM volumes in the prefrontal cortex and the precuneus, the uncus, and the superior temporal and occipital cortices than Met carriers. The Met homozygotes demonstrated a higher stress response in depression domain than Val/Val and Val/Met groups. A negative correlation between the middle frontal cortex GM volume and the SRI depression subscore was found. CONCLUSION:These findings indicate an interaction between genes and brain structure, and they suggest that differences in dorsolateral prefrontal GM volume related to the BDNF Val66Met SNP are associated with resilience to stressful life events, particularly in the dimension of emotion.

SUBMITTER: Kim SN

PROVIDER: S-EPMC3687052 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Impact of the BDNF Val66Met Polymorphism on Regional Brain Gray Matter Volumes: Relevance to the Stress Response.

Kim Sung Nyun SN Kang Do-Hyung DH Yun Je-Yeon JY Lee Tae Young TY Jung Wi Hoon WH Jang Joon Hwan JH Kwon Jun Soo JS

Psychiatry investigation 20130530 2

<h4>Objective</h4>Genetic imaging is used to investigate the mechanism by which genetic variants influence brain structure. In a previous study, a structural change of the dorsolateral prefrontal cortex was associated with symptom modulation in post-traumatic stress disorder patients. This study examined the effect of a polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF) on regional gray matter (GM) volumes and the correlations between the dorsolateral prefrontal GM volume ...[more]

PMID: 23798966

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Project description:Background:Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Methods:Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Results:Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. Conclusions:This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Dataset Information

Impact of the BDNF Val66Met Polymorphism on Regional Brain Gray Matter Volumes: Relevance to the Stress Response.

Publications

Impact of the BDNF Val66Met Polymorphism on Regional Brain Gray Matter Volumes: Relevance to the Stress Response.

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