Lifestyle and anxiety disorders: BDNF, a possible biomarker?

Authors

  • Tatiana Marins Farias Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil https://orcid.org/0000-0001-9319-5764
  • Sílvia Fernanda Lima de Moura Cal Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil https://orcid.org/0000-0002-8396-7940
  • Rebeca Ataide de Cerqueira Martagão Gesteira Hospital da Criança, Residente de Pediatria, Salvador, BA, Brasil
  • Ana Carolina Tavares Lopes Emergencista, Clínica Médica em Hospital da Bahia e Hospital Jorge Valente, Salvador, BA, Brasil
  • Danton Ferraz de Sousa Médico, Clínica Espaço Bom Viver, Salvador, BA, Brasil https://orcid.org/0000-0002-5996-001X
  • João Vitor Costa Freire Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil https://orcid.org/0000-0002-3449-4358
  • Ana Julia Bernardo Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil https://orcid.org/0009-0007-9445-1572

DOI:

https://doi.org/10.61661/BJLM.2023.v2.69

Keywords:

BDNF, anxiety, anxiety disorders, Brain-Derived Neurotrophic Factor, neurobiology, lifestyle, review

Abstract

Introduction: Anxiety disorders (AD) are brain disturbances related to neurotransmitter circuits and neuroanatomic changes that are aggravated by unhealthy lifestyle. In turn, the brain derived neurotrophic factor (BDNF), a neurotrophin responsible for cerebral plasticity, is related to alteration volume in some brain structures and it can be explained by some lifestyle factors. Objective: to analyze the relationship between BDNF and AD and describe possible damage to the psychic functions in individuals with these disorders. Methods: this was an integrative review of the literature of articles published between 2008 and 2018, selected in the bibliographic databases of PubMed, SciElo and LILACSResults: In total, 28 articles were selected, of studies conducted with humans and animals. The relationship between levels of BDNF, and AD was observed to have been approached, showing that the neurotrophic hypothesis could contribute to the physiopathology of ADs, including volumetric changes in regions of the brain, comprising psychic functions. Furthermore, studies have shown that the BDNF levels may reflect the effect of antidepressant or neuromodulation therapy, and that exposure to stressful factors may be related to individuals with this genetic variant being more vulnerable to developing AD. Conclusions: The data obtained in this research pointed towards an inverse relationship between BDNF levels and AD, and to the contribution of the  neurotrophic hypothesis to the neurobiology of these disturbances, including damage to the psychic functions. Whereas considering that other studies to not show this relationship, further studies need to be conducted to validate a possible association.

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Author Biographies

Tatiana Marins Farias, Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil

Sílvia Fernanda Lima de Moura Cal, Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil

Rebeca Ataide de Cerqueira, Martagão Gesteira Hospital da Criança, Residente de Pediatria, Salvador, BA, Brasil

Ana Carolina Tavares Lopes, Emergencista, Clínica Médica em Hospital da Bahia e Hospital Jorge Valente, Salvador, BA, Brasil

Danton Ferraz de Sousa, Médico, Clínica Espaço Bom Viver, Salvador, BA, Brasil

João Vitor Costa Freire, Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil

Ana Julia Bernardo, Faculdade de Medicina da União Metropolitana de Educação e Cultura, UNIME, Lauro de Freitas, BA, Brasil

References

American Psychiatric Association. Manual diagnóstico e estatístico de transtornos mentais: DSM-5. 5. ed. Porto Alegre: Artmed; 2014.

Lépine JP. The epidemiology of anxiety disorders: prevalence and societal costs. J Clin Psychiatry. 2002;63 Suppl 14:4-8. - PMID:12562112

Hu S, Tucker L, Wu C, Yang L. Beneficial effects of exercise on depression and anxiety during the covid-19 pandemic: a narrative review. Front Psychiatry. 2020;11:587557. https://doi.org/10.3389/fpsyt.2020.587557 - PMID:33329133 - PMCID:PMC7671962 DOI: https://doi.org/10.3389/fpsyt.2020.587557

Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015;17(3):327-35. https://doi.org/10.31887/dcns.2015.17.3/bbandelow PMID:26487813 - PMCID:PMC4610617 DOI: https://doi.org/10.31887/DCNS.2015.17.3/bbandelow

Twenge JM, Joiner TE. U.S. Census Bureau-assessed prevalence of anxiety and depressive symptoms in 2019 and during the 2020 covid-19 pandemic. Depress Anxiety. 2020;37(10):954-6. https://doi.org/10.1002/da.23077 - PMID:32667081 - PMCID:PMC7405486 DOI: https://doi.org/10.1002/da.23077

World Health Organization. World mental health report: transforming mental health for all. Geneva: World Health Organization; 2022. https://www.who.int/publications/i/item/9789240049338

Kim YK, Jeon SW. Neuroinflammation and the immune-kynurenine pathway in anxiety disorders. Curr Neuropharmacol. 2018;16(5):574-82. https://doi.org/10.2174/1570159x15666170913110426 - PMID:28901278 - PMCID:PMC5997870 DOI: https://doi.org/10.2174/1570159X15666170913110426

Martin EI, Ressler KJ, Binder E, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatr Clin North Am. 2009;32(3):549-75. https://doi.org/10.1016/j.psc.2009.05.004 - PMID:19716990 - PMCID:PMC3684250 DOI: https://doi.org/10.1016/j.psc.2009.05.004

Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22-34. https://doi.org/10.1038/nri.2015.5 PMID:26711676 - PMCID:PMC5542678 DOI: https://doi.org/10.1038/nri.2015.5

Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H. Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(1):112-9. https://doi.org/10.1016/j.pnpbp.2012.05.018 - PMID:22664354 DOI: https://doi.org/10.1016/j.pnpbp.2012.05.018

Calabrese F, Rossetti AC, Racagni G, Gass P, Riva MA, Molteni R. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front Cell Neurosci. 2014;8:430. https://doi.org/10.3389/fncel.2014.00430 - PMID:25565964 - PMCID:PMC4273623 DOI: https://doi.org/10.3389/fncel.2014.00430

Maron E, Nutt D. Biological predictors of pharmacological therapy in anxiety disorders. Dialogues Clin Neurosci. 2015;17(3):305-17. https://doi.org/10.31887/dcns.2015.17.3/emaron PMID:26487811 - PMCID:PMC4610615 DOI: https://doi.org/10.31887/DCNS.2015.17.3/emaron

Latsko MS, Gilman TL, Matt LM, Nylocks KM, Coifman KG, Jasnow AM. A novel interaction between tryptophan hydroxylase 2 (TPH2) gene polymorphism (rs4570625) and BDNF Val66Met predicts a high-risk emotional phenotype in healthy subjects. PLoS One. 2016;11(10):e0162585. https://doi.org/10.1371/journal.pone.0162585 - PMID:27695066 - PMCID:PMC5047464 DOI: https://doi.org/10.1371/journal.pone.0162585

Null G, Pennesi L. Diet and lifestyle intervention on chronic moderate to severe depression and anxiety and other chronic conditions. Complement Ther Clin Pract. 2017;29:189-93. https://doi.org/10.1016/j.ctcp.2017.09.007 - PMID:29122259 DOI: https://doi.org/10.1016/j.ctcp.2017.09.007

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097 - PMID:19621072 - PMCID:PMC2707599 DOI: https://doi.org/10.1371/journal.pmed.1000097

Lau JY, Goldman D, Buzas B, Hodgkinson C, Leibenluft E, Nelson E, Sankin L, Pine DS, Ernst M. BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents. Neuroimage. 2010;53(3):952-61. https://doi.org/10.1016/j.neuroimage.2009.11.026 - PMID:19931400 - PMCID:PMC2888869 DOI: https://doi.org/10.1016/j.neuroimage.2009.11.026

Carlino D, Francavilla R, Baj G, Kulak K, d'Adamo P, Ulivi S, Cappellani S, Gasparini P, Tongiorgi E. Brain-derived neurotrophic factor serum levels in genetically isolated populations: gender-specific association with anxiety disorder subtypes but not with anxiety levels or Val66Met polymorphism. PeerJ. 2015;3:e1252. https://doi.org/10.7717/peerj.1252 - PMID:26539329 PMCID:PMC4631459 DOI: https://doi.org/10.7717/peerj.1252

Molendijk ML, Bus BA, Spinhoven P, Penninx BW, Prickaerts J, Oude Voshaar RC, Elzinga BM. Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety. World J Biol Psychiatry. 2012;13(7):535-43. https://doi.org/10.3109/15622975.2011.587892 PMID:21888560 DOI: https://doi.org/10.3109/15622975.2011.587892

Andreatta M, Neueder D, Genheimer H, Schiele MA, Schartner C, Deckert J, Domschke K, Reif A, Wieser MJ, Pauli P. Human BDNF rs6265 polymorphism as a mediator for the generalization of contextual anxiety. J Neurosci Res. 2019;97(3):300-12. https://doi.org/10.1002/jnr.24345 PMID:30402941 DOI: https://doi.org/10.1002/jnr.24345

Jamal M, Van der Does W, Penninx BW. Effect of variation in BDNF Val(66)Met polymorphism, smoking, and nicotine dependence on symptom severity of depressive and anxiety disorders. Drug Alcohol Depend. 2015;148:150-7. https://doi.org/10.1016/j.drugalcdep.2014.12.032 PMID:25618300 DOI: https://doi.org/10.1016/j.drugalcdep.2014.12.032

Konishi Y, Tanii H, Otowa T, Sasaki T, Kaiya H, Okada M, Okazaki Y. The association of BDNF Val66Met polymorphism with trait anxiety in panic disorder. J Neuropsychiatry Clin Neurosci. 2014;26(4):344-51. https://doi.org/10.1176/appi.neuropsych.11120359 - PMID:26037856 DOI: https://doi.org/10.1176/appi.neuropsych.11120359

Chagnon YC, Potvin O, Hudon C, Préville M. DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women. Front Genet. 2015;6:230. https://doi.org/10.3389/fgene.2015.00230 - PMID:26175754 - PMCID:PMC4485183 DOI: https://doi.org/10.3389/fgene.2015.00230

Pallanti S, Tofani T, Zanardelli M, Di Cesare Mannelli L, Ghelardini C. BDNF and artemin are increased in drug-naïve non-depressed GAD patients: preliminary data. Int J Psychiatry Clin Pract. 2014;18(4):255-60. https://doi.org/10.3109/13651501.2014.940051 - PMID:24994477 DOI: https://doi.org/10.3109/13651501.2014.940051

Dalle Molle R, Portella AK, Goldani MZ, Kapczinski FP, Leistner-Segal S, Salum GA, Manfro GG, Silveira PP. Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels. Transl Psychiatry. 2012;2:e195. https://doi.org/10.1038/tp.2012.126 - PMID:23168995 - PMCID:PMC3565759 DOI: https://doi.org/10.1038/tp.2012.126

Wang Y, Zhang H, Li Y, Wang Z, Fan Q, Yu S, Lin Z, Xiao Z. BDNF Val66Met polymorphism and plasma levels in Chinese Han population with obsessive-compulsive disorder and generalized anxiety disorder. J Affect Disord. 2015;186:7-12. https://doi.org/10.1016/j.jad.2015.07.023 PMID:26209750 DOI: https://doi.org/10.1016/j.jad.2015.07.023

Montag C, Reuter M, Newport B, Elger C, Weber B. The BDNF Val66Met polymorphism affects amygdala activity in response to emotional stimuli: evidence from a genetic imaging study. Neuroimage. 2008;42(4):1554-9. https://doi.org/10.1016/j.neuroimage.2008.06.008 PMID:18603005 DOI: https://doi.org/10.1016/j.neuroimage.2008.06.008

Enoch MA, White KV, Waheed J, Goldman D. Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders. Depress Anxiety. 2008;25(5):383-92. https://doi.org/10.1002/da.20378 - PMID:17941097 DOI: https://doi.org/10.1002/da.20378

Montag C, Basten U, Stelzel C, Fiebach CJ, Reuter M. The BDNF Val66Met polymorphism and anxiety: support for animal knock-in studies from a genetic association study in humans. Psychiatry Res. 2010;179(1):86-90. https://doi.org/10.1016/j.psychres.2008.08.005 PMID:20478625 DOI: https://doi.org/10.1016/j.psychres.2008.08.005

Vandermeer MRJ, Sheikh HI, Singh SS, Klein DN, Olino TM, Dyson MW, Bufferd SJ, Hayden EP. The BDNF gene val66met polymorphism and behavioral inhibition in early childhood. Soc Dev. 2018;27(3):543-54. https://doi.org/10.1111/sode.12292 - PMID:30245555 - PMCID:PMC6142175 DOI: https://doi.org/10.1111/sode.12292

Bird CW, Baculis BC, Mayfield JJ, Chavez GJ, Ontiveros T, Paine DJ, Marks AJ, Gonzales AL, Ron D, Valenzuela CF. The brain-derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus. Genes Brain Behav. 2019;18(3):e12484. https://doi.org/10.1111/gbb.12484 - PMID:29691979 - PMCID:PMC6291361 DOI: https://doi.org/10.1111/gbb.12484

McGregor NW, Dimatelis JJ, Van Zyl PJ, Hemmings SMJ, Kinnear C, Russell VA, Stein DJ, Lochner C. A translational approach to the genetics of anxiety disorders. Behav Brain Res. 2018;341:91-7. https://doi.org/10.1016/j.bbr.2017.12.030 - PMID:29288745 DOI: https://doi.org/10.1016/j.bbr.2017.12.030

Mueller SC, Aouidad A, Gorodetsky E, Goldman D, Pine DS, Ernst M. Gray matter volume in adolescent anxiety: an impact of the brain-derived neurotrophic factor Val(66)Met polymorphism? J Am Acad Child Adolesc Psychiatry. 2013;52(2):184-95. https://doi.org/10.1016/j.jaac.2012.11.016 - PMID:23357445 - PMCID:PMC3570270 DOI: https://doi.org/10.1016/j.jaac.2012.11.016

Janke KL, Cominski TP, Kuzhikandathil EV, Servatius RJ, Pang KC. Investigating the role of hippocampal BDNF in anxiety vulnerability using classical eyeblink conditioning. Front Psychiatry. 2015;6:106. https://doi.org/10.3389/fpsyt.2015.00106 - PMID:26257661 - PMCID:PMC4513557 DOI: https://doi.org/10.3389/fpsyt.2015.00106

Miao Z, Mao F, Liang J, Szyf M, Wang Y, Sun ZS. Anxiety-related behaviours associated with microRNA-206-3p and BDNF expression in pregnant female mice following psychological social stress. Mol Neurobiol. 2018;55(2):1097-111. https://doi.org/10.1007/s12035-016-0378-1 PMID:28092086 DOI: https://doi.org/10.1007/s12035-016-0378-1

Kumari A, Singh P, Baghel MS, Thakur MK. Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain. Physiol Behav. 2016;158:34-42. https://doi.org/10.1016/j.physbeh.2016.02.032 - PMID:26921097 DOI: https://doi.org/10.1016/j.physbeh.2016.02.032

Tocchetto A, Salum GA, Blaya C, Teche S, Isolan L, Bortoluzzi A, Rebelo e Silva R, Becker JA, Bianchin MM, Rohde LA, Leistner-Segal S, Manfro GG. Evidence of association between Val66Met polymorphism at BDNF gene and anxiety disorders in a community sample of children and adolescents. Neurosci Lett. 2011;502(3):197-200. https://doi.org/10.1016/j.neulet.2011.07.044 PMID:21839144 DOI: https://doi.org/10.1016/j.neulet.2011.07.044

Sharpley CF, Christie DRH, Bitsika V, Andronicos NM, Agnew LL, Richards TM, McMillan ME. Comparing a genetic and a psychological factor as correlates of anxiety, depression, and chronic stress in men with prostate cancer. Support Care Cancer. 2018;26(9):3195-200. https://doi.org/10.1007/s00520-018-4183-4 - PMID:29603029 DOI: https://doi.org/10.1007/s00520-018-4183-4

Bahi A. Sustained lentiviral-mediated overexpression of microRNA124a in the dentate gyrus exacerbates anxiety- and autism-like behaviors associated with neonatal isolation in rats. Behav Brain Res. 2016;311:298-308. https://doi.org/10.1016/j.bbr.2016.05.033 - PMID:27211062 DOI: https://doi.org/10.1016/j.bbr.2016.05.033

Moreira FP, Fabião JD, Bittencourt G, Wiener CD, Jansen K, Oses JP, Quevedo LA, Souza LDM, Crispim D, Portela LV, Pinheiro RT, Lara DR, Kaster MP, Silva RA, Ghisleni G. The met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder. Psychiatr Genet. 2015;25(5):201-7. https://doi.org/10.1097/ypg.0000000000000097 PMID:26110341 DOI: https://doi.org/10.1097/YPG.0000000000000097

Uguz F, Sonmez EO, Sahingoz M, Gokmen Z, Basaran M, Gezginc K, Sonmez G, Kaya N, Erdem SS, Cicekler H, Tasyurek E. Maternal generalized anxiety disorder during pregnancy and fetal brain development: a comparative study on cord blood brain-derived neurotrophic factor levels. J Psychosom Res. 2013;75(4):346-50. https://doi.org/10.1016/j.jpsychores.2013.04.010 PMID:24119941 DOI: https://doi.org/10.1016/j.jpsychores.2013.04.010

Ball S, Marangell LB, Lipsius S, Russell JM. Brain-derived neurotrophic factor in generalized anxiety disorder: results from a duloxetine clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 2013;43:217-21. https://doi.org/10.1016/j.pnpbp.2013.01.002 - PMID:23313564 DOI: https://doi.org/10.1016/j.pnpbp.2013.01.002

Lu R, Zhang C, Liu Y, Wang L, Chen X, Zhou X. The effect of bilateral low-frequency rTMS over dorsolateral prefrontal cortex on serum brain-derived neurotropic factor and serotonin in patients with generalized anxiety disorder. Neurosci Lett. 2018;684:67-71. https://doi.org/10.1016/j.neulet.2018.07.008 - PMID:30008380 DOI: https://doi.org/10.1016/j.neulet.2018.07.008

Ernst C, Marshall CR, Shen Y, Metcalfe K, Rosenfeld J, Hodge JC, Torres A, Blumenthal I, Chiang C, Pillalamarri V, Crapper L, Diallo AB, Ruderfer D, Pereira S, Sklar P, Purcell S, Wildin RS, Spencer AC, Quade BF, Harris DJ, Lemyre E, Wu B-L, Stavropoulos DJ, Geraghty MT, Shaffer LG, Morton CC, Scherer SW, Gusella JF, Talkowski, M. E. Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity. Arch Gen Psychiatry. 2012;69(12):1238–1246. https://doi.org/10.1001/archgenpsychiatry.2012.660 DOI: https://doi.org/10.1001/archgenpsychiatry.2012.660

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2023-10-16

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Farias TM, Cal SFL de M, Cerqueira RA de, Lopes ACT, Sousa DF de, Freire JVC, Bernardo AJ. Lifestyle and anxiety disorders: BDNF, a possible biomarker?. B J Lifestyle Med [Internet]. 2023 Oct. 16 [cited 2024 Nov. 21];2:1-38. Available from: https://publicacoes.cbmev.org.br/bjlm/article/view/69

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Saúde Mental e Manejo do Estresse

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