The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression
Abstract
BACKGROUND: The role of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of affective disorders such as depression has been controversial. Mounting evidence comes from structural imaging, that the functional BDNF Val66Met polymorphism influences the hippocampal volume with carriers of the 66Met allele (Val/Met and Met/Met group) having smaller hippocampi. Given that stress-induced atrophy of the hippocampus is associated with the pathogenesis of affective disorders, the functional BDNF Val66Met polymorphism could be an incremental risk factor. METHOD: Eighty-seven healthy Caucasian participants underwent structural imaging and were genotyped for the BDNF Val66Met polymorphism. Data were analysed by means of voxel-based morphometry (VBM). RESULTS: Region of interest (ROI) analyses revealed an association between the 66Met allele and smaller parahippocampal volumes and a smaller right amygdala. In addition, the whole-brain analysis showed that the thalamus, fusiformus gyrus and several parts of the frontal gyrus were smaller in 66Met allele carriers. CONCLUSIONS: This study demonstrates that the impact of the BDNF Val66Met polymorphism is not confined to the hippocampus but also extends to the parahippocampal gyrus and the amygdala.
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The Met allele of BDNF Val66Met has been associated with reduced amygdala and hippocampus volume.
“as well as reduced amygdala and hippocampus volume (Montag et al. 2009).”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Montag et al. 2009
Cites
A psychobiological model of temperament and character
Cloninger, C. R. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820240059008 · Cited by 5,458 · see citing works
Decreased serum brain-derived neurotrophic factor levels in major depressed patients
Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J.-M. (2002) · Psychiatry Research · doi:10.1016/s0165-1781(02)00005-7 · Cited by 1,232 · see citing works
Pezawas, L., Verchinski, B. A., Mattay, V. S., Callicott, J. H., Kolachana, B. S., Straub, R. E., Egan, M. F., Meyer-Lindenberg, A., & Weinberger, D. R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2680-04.2004 · Cited by 890 · see citing works
Genetic covariation between neuroticism and the symptoms of anxiety and depression
Jardine, R., Martin, N. G., Henderson, A. S., & Rao, D. C. (1984) · Genetic Epidemiology · doi:10.1002/gepi.1370010202 · Cited by 351 · see citing works
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Miranda, M., Morici, J. F., Zanoni, M. B., & Bekinschtein, P. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00363 · Cited by 1,416 · see citing works
Colucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207777 · Cited by 991 · see citing works
Gene–environment interactions: early life stress and risk for depressive and anxiety disorders
Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2151-x · Cited by 269 · see citing works
“2010), as well as reduced amygdala and hippocampus volume (Montag et al. 2009).”
BackgroundVoxelwise meta-analysis of gray matter reduction in major depressive disorder
Du, M.-Y., Wu, Q.-Z., Yue, Q., Li, J., Liao, Y., Kuang, W.-H., Huang, X.-Q., Chan, R. C. K., Mechelli, A., & Gong, Q.-Y. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.09.014 · Cited by 237 · see citing works
Boersma, G. J., Lee, R. S., Cordner, Z. A., Ewald, E. R., Purcell, R. H., Moghadam, A. A., & Tamashiro, K. L. (2014) · Epigenetics · doi:10.4161/epi.27558 · Cited by 172 · see citing works
Common Variants in Psychiatric Risk Genes Predict Brain Structure at Birth
Knickmeyer, R. C., Wang, J., Zhu, H., Geng, X., Woolson, S., Hamer, R. M., Konneker, T., Lin, W., Styner, M., & Gilmore, J. H. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhs401 · Cited by 149 · see citing works
Mueller, S. C., Aouidad, A., Gorodetsky, E., Goldman, D., Pine, D. S., & Ernst, M. (2013) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2012.11.016 · Cited by 103 · see citing works
Carballedo, A., Amico, F., Ugwu, I., Fagan, A. J., Fahey, C., Morris, D., Meaney, J. F., Leemans, A., & Frodl, T. (2012) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32060 · Cited by 95 · see citing works
Lotrich, F. E., Albusaysi, S., & Ferrell, R. E. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.263 · Cited by 92 · see citing works
Brain structures implicated in inflammation-associated depression
Harrison, N. A. (2016) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2016_30 · Cited by 74 · see citing works
Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology
van Velzen, L. S., Schmaal, L., Jansen, R., Milaneschi, Y., Opmeer, E. M., Elzinga, B. M., van der Wee, N. J. A., Veltman, D. J., & Penninx, B. W. J. H. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw086 · Cited by 58 · see citing works
A biological perspective on differences and similarities between burnout and depression
Orosz, A., Federspiel, A., Haisch, S., Seeher, C., Dierks, T., & Cattapan, K. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.005 · Cited by 55 · see citing works
Slyepchenko, A., Brunoni, A. R., McIntyre, R. S., Quevedo, J., & Carvalho, A. F. (2016) · Current Molecular Medicine · doi:10.2174/1566524016666160126144601 · Cited by 14 · see citing works
- Authors
- Montag, C., Weber, B., Fliessbach, K., Elger, C., & Reuter, M.
- Affiliations
- University of Bonn (DE)
- University Hospital Bonn (DE)
- Corresponding author
- Montag, C.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2009-04-01
- Volume
- 39
- Issue
- 11
- Pages
- 1831-1839
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2099280287
- Cited by
- 165
- References
- 4
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 10 · 2016: 16 · 2015: 13 · 2014: 18 · 2013: 17 · 2012: 13
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- BDNF Val66Met polymorphism, brain-derived neurotrophic factor, parahippocampal gyrus, amygdala, hippocampal volume, brain structure, genetic risk factors, depression, thalamus, fusiform gyrus, frontal gyrus, voxel-based morphometry
- MeSH terms
- Adult, Alleles, Amygdala, Atrophy, Brain, Brain Mapping, Depressive Disorder, Dominance, Cerebral, Female, Frontal Lobe, Genotype, Genetic Carrier Screening, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Polymorphism, Genetic, Reference Values, Risk Factors, Thalamus, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease, Parahippocampal Gyrus, Young Adult
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