Citation

Youssef MM, Underwood MD, Huang YY, Hsiung SC, Liu Y, Simpson NR, Bakalian MJ, Rosoklija GB, Dwork AJ, Arango V, Mann JJ. Int. J. Neuropsychopharmacol. 2018; 21(6): 528-538.

Affiliation

Department of Radiology, Columbia University, New York, NY, USA.

Copyright

(Copyright © 2018, Cambridge University Press)

DOI

10.1093/ijnp/pyy008

PMID

29432620

Abstract

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces BDNF protein levels. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both MDD and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD.

METHODS: BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC, BA24), caudal brainstem and rostral brainstem. The relationships between these measures and MDD, death by suicide and reported ELA were examined.

RESULTS: Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or ELA was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to ELA and/or died by suicide compared to non-suicide decedents and no reported ELA.

CONCLUSIONS: This study provides further evidence implicating low brain BDNF and the BDNF Met allele in major depression risk. Future studies should seek to determine how altered BDNF expression contributes to depression and suicide.

Language: en

Keywords

brain-derived neurotrophic factor; childhood adversity; depression; single nucleotide polymorphism; suicide