Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer
Open accessAbstract
Background Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals particularly vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms. Methods Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions. Results There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001). Conclusion The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment. Limitation BDNF genotype is an indirect measure of BDNF protein levels.
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The BDNF Met allele changes the link between CRP and depressive symptoms that are cognitive.
“such as the BDNF Met allele, which has been shown to moderate the association between CRP and cognitive depressive symptoms (Dooley et al., 2016).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Dooley et al., 2016
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Cites
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023 · see citing works
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,152 · see citing works
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · see citing works
C-reactive protein: a critical update
Pepys, M. B., & Hirschfield, G. M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18921 · Cited by 4,576 · see citing works
Structural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413 · see citing works
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
C-reactive protein: a critical update
Pepys, M. B., & Hirschfield, G. M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318921 · Cited by 3,436 · see citing works
Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766 · see citing works
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206 · see citing works
Neural mechanisms of the cognitive model of depression.
Disner, S. G., Beevers, C. G., Haigh, E. A. P., & Beck, A. T. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3027 · Cited by 1,718 · see citing works
Immune modulation of learning, memory, neural plasticity and neurogenesis
Yirmiya, R., & Goshen, I. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.015 · Cited by 1,483 · see citing works
Twenty years of research on cytokine-induced sickness behavior
Dantzer, R., & Kelley, K. W. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.09.006 · Cited by 1,420 · see citing works
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365 · see citing works
Depression and cancer mortality: a meta-analysis
Pinquart, M., & Duberstein, P. R. (2010) · Psychological Medicine · doi:10.1017/s0033291709992285 · Cited by 1,083 · cited 1× · see citing works
“Depression reduces quality of life, and may also lead to shorter survival time in women with breast cancer (Pinquart and Duberstein, 2011).”
Haroon, E., Raison, C. L., & Miller, A. H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.205 · Cited by 1,000 · see citing works
Miller, A. H., Haroon, E., Raison, C. L., & Felger, J. C. (2013) · Depression and Anxiety · doi:10.1002/da.22084 · Cited by 892 · see citing works
(1991) · Sleep · doi:10.1093/sleep/14.4.331 · Cited by 874 · cited 4× · see citing works
“PSQI .50a .34a .36a .54a .03 .04 .04 .08 .08 .01 .15 .12 .21c Note.”
InfluentialCapuron, L. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00407-9 · Cited by 797 · see citing works
Neuroendocrine-Immune Mechanisms of Behavioral Comorbidities in Patients With Cancer
Miller, A. H., Ancoli‐Israel, S., Bower, J. E., Capuron, L., & Irwin, M. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.10.7805 · Cited by 609 · see citing works
Self-citationCytokines and psychopathology: Lessons from interferon-α
Capuron, L., & Miller, A. H. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.02.009 · Cited by 562 · see citing works
Gimeno, D., Kivimäki, M., Brunner, E. J., Elovainio, M., De Vogli, R., Steptoe, A., Kumari, M., Lowe, G. D. O., Rumley, A., Marmot, M. G., et al. (2009) · Psychological Medicine · doi:10.1017/s0033291708003723 · Cited by 561 · see citing works
Bower, J., Ganz, P., Irwin, M. R., Kwan, L., Breen, E., & Cole, S. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.1154 · Cited by 497 · see citing works
Self-citationNeuropsychiatric Adverse Effects of Interferon-??: Recognition and Management
Raison, C. L., Demetrashvili, M., Capuron, L., & Miller, A. H. (2005) · CNS Drugs · doi:10.2165/00023210-200519020-00002 · Cited by 483 · see citing works
Musselman, D. L., Miller, A. H., Porter, M. R., Manatunga, A. K., Gao, F., Penna, S., Pearce, B. D., Landry, J. C., Glover, S. G., McDaniel, J. S., et al. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.8.1252 · Cited by 445 · see citing works
Eisenberger, N. I., Inagaki, T. K., Mashal, N. M., & Irwin, M. R. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.12.009 · Cited by 413 · see citing works
Bower, J. E., & Lamkin, D. M. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.06.011 · Cited by 373 · see citing works
Self-citationSoluble receptors for tumour necrosis factor in clinical laboratory diagnosis
Diez‐Ruiz, A., Tilz, G. P., Zangerle, R., Baier‐Bitterlich, G., WACHTER, H., & Fuchs, D. (1995) · European Journal Of Haematology · doi:10.1111/j.1600-0609.1995.tb01618.x · Cited by 306 · see citing works
Henselmans, I., Helgeson, V. S., Seltman, H. J., de Vries, J., Sanderman, R., & Ranchor, A. V. (2010) · Health Psychology · doi:10.1037/a0017806 · Cited by 298 · see citing works
Cytokines mediated inflammation and decreased neurogenesis in animal models of depression
Song, C., & Wang, H. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.06.020 · Cited by 289 · see citing works
Acute inflammation and negative mood: mediation by cytokine activation
Wright, C. E., Strike, P. C., Brydon, L., & Steptoe, A. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.10.003 · Cited by 287 · see citing works
Neurobiological effects of exercise on major depressive disorder: A systematic review
Schuch, F. B., Deslandes, A. C., Stubbs, B., Gosmann, N. P., Silva, C. T. B. D., & Fleck, M. P. D. A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.11.012 · Cited by 279 · see citing works
Computational identification of gene–social environment interaction at the human <i>IL6</i> locus
Cole, S. W., Arevalo, J. M. G., Takahashi, R., Sloan, E. K., Lutgendorf, S. K., Sood, A. K., Sheridan, J. F., & Seeman, T. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911515107 · Cited by 256 · see citing works
Self-citationRole of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice.
Bluthé, R., Michaud, B., Poli, V., & Dantzer, R. (2000) · Physiology and Behavior · doi:10.1016/s0031-9384(00)00269-9 · Cited by 239 · see citing works
Sleep disturbance, inflammation and depression risk in cancer survivors
Irwin, M. R., Olmstead, R. E., Ganz, P. A., & Haque, R. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.05.002 · Cited by 173 · see citing works
Self-citationThe Factor Structure of the Beck Depression Inventory–II
Vanheule, S., Desmet, M., Groenvynck, H., Rosseel, Y., & Fontaine, J. R. J. (2008) · Assessment · doi:10.1177/1073191107311261 · Cited by 171 · see citing works
A psychometric evaluation of the BDI-II in treatment-seeking substance abusers
Buckley, T. C., Parker, J. D., & Heggie, J. (2001) · Journal of Substance Abuse Treatment · doi:10.1016/s0740-5472(00)00169-0 · Cited by 156 · see citing works
Does tumor necrosis factor-alpha (TNF-α) play a role in post-chemotherapy cerebral dysfunction?
Ganz, P. A., Bower, J. E., Kwan, L. C., Castellon, S. A., Silverman, D. H. S., Geist, C. L., Breen, E. C., Irwin, M. R., & Cole, S. W. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.07.015 · Cited by 156 · see citing works
Self-citationBiomarkers of depression in cancer patients
Jehn, C. F., Kuehnhardt, D., Bartholomae, A., Pfeiffer, S., Krebs, M., Regierer, A. C., Schmid, P., Possinger, K., & Flath, B. C. (2006) · Cancer · doi:10.1002/cncr.22294 · Cited by 139 · see citing works
Ganz, P. A., Petersen, L., Bower, J. E., & Crespi, C. M. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.3866 · Cited by 103 · see citing works
Self-citationPertl, M. M., Hevey, D., Boyle, N. T., Hughes, M. M., Collier, S., O’Dwyer, A.-M., Harkin, A., Kennedy, M. J., & Connor, T. J. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.07.177 · Cited by 97 · see citing works
Ganz, P. A., Petersen, L., Castellon, S. A., Bower, J. E., Silverman, D. H. S., Cole, S. W., Irwin, M. R., & Belin, T. R. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.56.1662 · Cited by 97 · see citing works
Self-citationLotrich, F. E., Albusaysi, S., & Ferrell, R. E. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.263 · Cited by 92 · see citing works
Soygür, H., Palaoǧlu, Ö., Akarsu, E. S., Cankurtaran, E. Ş., Özalp, E., Turhan, L., & Ayhan, I. H. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2007.05.001 · Cited by 84 · see citing works
BDNF val66met affects hippocampal volume and emotion-related hippocampal memory activity
Molendijk, M. L., van Tol, M., Penninx, B. W. J. H., van der Wee, N. J. A., Aleman, A., Veltman, D. J., Spinhoven, P., & Elzinga, B. M. (2012) · Translational Psychiatry · doi:10.1038/tp.2011.72 · Cited by 77 · see citing works
The BDNF Val66Met polymorphism is associated with rumination in healthy adults.
Beevers, C. G., Wells, T. T., & McGeary, J. E. (2009) · Emotion · doi:10.1037/a0016189 · Cited by 74 · see citing works
Determinants of suicidal ideation in patients with breast cancer
Kim, J., Jang, J., Stewart, R. J., Kim, S., Kim, S., Kang, H., Shin, I., Park, M., Yoon, J., & Yoon, J. (2013) · Psycho-Oncology · doi:10.1002/pon.3367 · Cited by 68 · see citing works
Minelli, A., Zanardini, R., Bonvicini, C., Sartori, R., Pedrini, L., Gennarelli, M., & Bocchio‐Chiavetto, L. (2011) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-011-0189-3 · Cited by 66 · see citing works
Plasma BDNF concentration, Val66Met genetic variant and depression- related personality traits
Terracciano, A., Martin, B., Ansari, D., Tanaka, T., Ferrucci, L., Maudsley, S., Mattson, M. P., & Costa, P. T. (2010) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2010.00579.x · Cited by 63 · see citing works
Mahmoud, R. A. K., El-Gendi, H. I., & Ahmed, H. (2004) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2004.11.002 · Cited by 52 · see citing works
Interrelationship of depression, stress and inflammation in cancer patients: A preliminary study
Archer, J. A., Hutchison, I. L., Dorudi, S., Stansfeld, S. A., & Korszun, A. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.05.023 · Cited by 41 · see citing works
Depressive Symptom Trajectories During and After Adjuvant Treatment for Breast Cancer
Donovan, K. A., Gonzalez, B. D., Small, B. J., Andrykowski, M. A., & Jacobsen, P. B. (2013) · Annals of Behavioral Medicine · doi:10.1007/s12160-013-9550-2 · Cited by 39 · see citing works
BDNF Promoter Methylation Associated with Suicidal Ideation in Patients with Breast Cancer
Kim, J., Kang, H., Kim, S.-Y., Kim, S., Shin, I., Kim, H. R., Park, M., Shin, M., Yoon, J.-H., & Yoon, J.-S. (2015) · The International Journal of Psychiatry in Medicine · doi:10.1177/0091217415574439 · Cited by 32 · see citing works
Herbert, J., Ban, M., Brown, G. W., Harris, T. O., Ogilvie, A. D., Uher, R., & Craig, T. (2012) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.111.107037 · Cited by 30 · see citing works
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Dooley, L. N., Kuhlman, K. R., Robles, T. F., Eisenberger, N. I., Craske, M. G., & Bower, J. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.006 · Cited by 176 · see citing works
Self-citationVal66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression
Caldieraro, M. A., McKee, M., Leistner-Segal, S., Vares, E. A., Kubaski, F., Spanemberg, L., Brusius-Facchin, A. C., Fleck, M. P., & Mischoulon, D. (2018) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2017.1347713 · Cited by 39 · see citing works
- Authors
- Dooley, L. N., Ganz, P. A., Cole, S. W., Crespi, C. M., & Bower, J. E.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Dooley, Larissa N.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 197
- Pages
- 43-50
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC4836957
- OpenAlex
- W2290717075
- Cited by
- 50
- References
- 55
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (P30 CA 016042, R01 CA 109650)
- National Institute of General Medical Sciences (T32 GM 08903)
- Catholic Medical Center
- National Institute on Aging (T32-AG033533, P30- AG028748)
- Breast Cancer Research Foundation
- National Institutes of Health
- California Center for Population Research, University of California, Los Angeles
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- BDNF Val66Met polymorphism, breast cancer, depressive symptoms, inflammation, C-reactive protein, brain-derived neurotrophic factor, neuroplasticity, genetic susceptibility, breast cancer survivors, women
- MeSH terms
- Adult, Aged, Alleles, Breast Neoplasms, C-Reactive Protein, Depression, Female, Genotype, Humans, Inflammation, Middle Aged, Polymorphism, Genetic, Surveys and Questionnaires, Risk Factors, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease
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