Variation in brain-derived neurotrophic factor (BDNF) gene is associated with symptoms of depression

Background: Brain-derived neurotrophic factor (BDNF) is putatively involved in the pathophysiology of depression. This study examined associations between BDNF genotype at the Val66Met locus, depression symptoms, and serum BDNF levels. Methods: Twenty-eight subjects in the primary study (25 female, 3 male) completed diagnostic interviews, self-report questionnaires, and provided blood samples for serum BDNF quantification and buccal cell samples for genotyping. Data from a second sample of 189 subjects (94 female, 95 male) were also analyzed. Results: The Val/Val genotype was associated with higher scores on the Cognitive-Affective factor of the Beek Depression Inventory-II (BDI-II) in the primary sample. No evidence was found for association between genotype and serum BDNF in this sample. Consistent with the primary study, Val/Val genotype was associated with higher total BDI-II scores, Cognitive-Affective factor scores, and Somatic-Vegetative factor scores, in the second sample. Serum BDNF measures were not available for the second sample. Limitations: The mechanism through which BDNF genotype translates into (putative) differences in depression symptoms is not known. Conclusions: In contrast to case-control association studies, we demonstrate two changes in the operationalization of the phenotype. Additionally, we found an association between Val/Val genotype and higher levels of depression symptoms. This result is distinct from an association between BDNF genotype and diagnosis of depression, and it may help to clarify our understanding of genetic liability to depression, which will ultimately lead to more nuanced and effective treatment strategies. (C) 2008 Elsevier B.V. All rights reserved.