Estilo de vida y trastornos de ansiedad: ¿ BDNF, posible biomarcador?
DOI:
https://doi.org/10.61661/BJLM.2023.v2.69Palabras clave:
BDNF, ansiedad, trastornos de ansiedad, factor neurotrófico derivado del encéfalo, neurobiología, estilo de vida, revisiónResumen
Introducción: Los trastornos de ansiedad (TA) están asociados con alteraciones cerebrales relacionadas con neurotransmisores y cambios neuroanatómicos, agravados por un estilo de vida poco saludable. El factor neurotrófico derivado del cerebro (BDNF), que influye en la plasticidad cerebral, puede relacionarse con cambios en el volumen de estructuras cerebrales. Objetivo: El estudio busca analizar la conexión entre BDNF y los TA, así como describir las posibles consecuencias negativas en las funciones psicológicas de quienes padecen estos trastornos. Metodología: Se revisaron estudios publicados entre 2008 y 2018 en PubMed, SciElo y LILACS. Resultados: Se incluyeron 28 artículos que investigaron tanto en humanos como en animales. Estos estudios exploraron la relación entre los niveles de BDNF y los TA, sugiriendo que la hipótesis neurotrófica podría contribuir a comprender la fisiopatología de los TA, incluyendo cambios en regiones cerebrales relacionadas con funciones psicológicas. Además, se encontró que los niveles de BDNF podrían reflejar el impacto de tratamientos antidepresivos o de neuromodulación, y que la exposición a factores estresantes podría aumentar la vulnerabilidad a TA en personas con ciertas variantes genéticas. Conclusión: En resumen, los resultados sugieren una posible relación inversa entre los niveles de BDNF y los TA, destacando la importancia de la hipótesis neurotrófica en la neurobiología de estos trastornos y su influencia en las funciones psicológicas. Sin embargo, se necesita más investigación para validar esta asociación en su totalidad.
Métricas
Citas
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
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2023 Tatiana Marins Farias, Sílvia Fernanda Lima de Moura Cal, Rebeca Ataide de Cerqueira, Ana Carolina Tavares Lopes, Danton Ferraz de Sousa, João Vitor Costa Freire, Ana Julia Bernardo
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial 4.0.
Brazilian Journal of Lifestyle Medicine = Revista Brasileira de Medicina do Estilo de Vida permite que o(s) autor(es) mantenha(m) seus direitos autorais.
