BDNF variation and mood disorders: A novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects

  • Jiang X
  • Xu K
  • Hoberman J
 et al. 
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The brain-derived neurotrophic factor (BDNF) gene is critical for neuronal function and survival, and is likely to be important in psychiatric disorders. In this study, we used single-nucleotide polymorphism (SNP) discovery, functional analyses, and genetic association studies to better understand the potential role of BDNF sequence variation in behavior. Screening 480 unrelated individuals for SNPs and genotyping was performed in US Caucasian, American Indian, and African American populations. Lifetime DSM-III-R psychiatric diagnoses were assigned and the Tridimensional Personality Questionnaire (TPQ) was administered to measure anxious temperament (harm avoidance (HA)) and novelty seeking (NS). A novel SNP (-281 C>A) in promoter 1 was discovered that had decreased DNA binding in vitro and decreased basal reporter gene activity in transfected rat hippocampal neurons. The frequency of the -281 A allele was 0.03 in a Caucasian sample, but was virtually absent in other populations. Association analyses in a community-based sample showed that individuals with the -281 A allele (13 heterozygotes) had lower TPQ HA (F=4.8, p

Author-supplied keywords

  • Anxiety
  • Brain-derived neurotrophic factor
  • Depression
  • Gene
  • Polymorphism
  • Promoter

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  • Xueying Jiang

  • Ke Xu

  • Joelle Hoberman

  • Feng Tian

  • Aimee J. Marko

  • Juwaria F. Waheed

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