Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide
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Abstract
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.
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The BDNF Val66Met polymorphism is associated with cognitive processes and cognitive impairment in neurodegenerative disease such as Parkinson's disease and Alzheimer's disease, and with several brain disorders including MDD, bipolar disorder, epilepsy, schizophrenia, aging and dementia, and stroke.
“More specifically, BDNF Val66Met polymorphism is associated with cognitive processes [112,123,124,125,126,127], and cognitive impairment in neurodegenerative disease, such as Parkinson’s disease (PD) [128,129] and AD [130,131], and even more with several brain disorders, including MDD and bipolar disorder [132,133,134,135,136,137], epilepsy [138,139,140], schizophrenia [125,141,142,143,144], aging”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [134]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredLow brain BDNF and the BDNF Met allele are implicated in major depression risk.
“providing further evidence implicating low brain BDNF and the BDNF Met allele in major depression risk (Youssef et al. 2018).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Youssef et al. 2018
Subjects with the Met allele of the Bdnf gene have an increased risk for depression.
“Finally, a recent study showed that subjects with the Met allele of the Bdnf gene had an increased risk for depression (Youssef et al. 2018).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Youssef et al. 2018
Depressed patients have lower BDNF levels in the anterior cingulate cortex and caudal brainstem compared to non-depressed subjects.
“post-mortem analyses showed that depressed patients also have lower BDNF levels in the anterior cingulate cortex (ACC) and the caudal brainstem compared to non-depressed subjects”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Youssef et al. 2018
Subjects with the Met allele of the BDNF gene are more likely to develop depression.
“Finally, a recent paper showed that subjects with the Met allele of the BDNF gene are more likely to develop depression [134].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [134]
The BDNF gene Met allele increases risk for suicidal behavior, particularly in depressed individuals and those exposed to early-life stress, where it may act by loss of ACC volume and altered decision-making or depression circuitry.
“The BDNF gene Met allele, a part of BDNF functional polymorphism (rs6265), increases the risk for suicidal behavior (183, 184), particularly in depressed individuals (185) and in those exposed to early-life stress (186, 187), where it may do so by loss of ACC volume (188) and altered decision-making or depression circuitry.”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [187]
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- Authors
- Youssef, M. M., Underwood, M. D., Huang, Y.-Y., Hsiung, S.-C., Liu, Y., Simpson, N. R., Bakalian, M. J., Rosoklija, G. B., Dwork, A. J., Arango, V., & Mann, J. J.
- Affiliations
- New York State Psychiatric Institute (US)
- Macedonian Academy of Sciences and Arts (MK)
- Corresponding author
- Underwood, Mark D
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-08
- Volume
- 21
- Issue
- 6
- Pages
- 528-538
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC6007393
- OpenAlex
- W2950435009
- Cited by
- 183
- References
- 110
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 20 · 2023: 22 · 2022: 35 · 2021: 49 · 2020: 23 · 2019: 14 · 2018: 5
- FWCI
- 14.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, public-domain)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH40210, MH62185, MH90964, MH64168)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- brain-derived neurotrophic factor, BDNF Val66Met polymorphism, major depressive disorder, suicide, childhood adversity, anterior cingulate cortex, dorsolateral prefrontal cortex, caudal brainstem, postmortem brain, genetic risk
- MeSH terms
- Adult Survivors of Child Adverse Events, Adult, Alleles, Brain, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Suicide, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genetic Association Studies
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