Marco Antonio Caldieraro1,2, Madison McKee3, Sandra Leistner-Segal4,5, Edgar Arrua Vares6, Francyne Kubaski7,8,9, Lucas Spanemberg6,10, Ana Carolina Brusius-Facchin4, Marcelo P Fleck2,6, David Mischoulon3,11. 1. a Department of Psychiatry , Massachusetts General Hospital , Boston , MA , USA. 2. b Department of Psychiatry , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brasil. 3. c Depression Clinical and Research Program , Massachusetts General Hospital , Boston , MA , USA. 4. d Medical Genetics Service, Molecular Genetics Laboratory , Hospital de Clínicas de Porto Alegre , Porto Alegre , Brasil. 5. e Experimental Research Center , B.R.A.I.N. Laboratory, Hospital de Clínicas de Porto Alegre , Porto Alegre , Brasil. 6. f Programa de Pós-Graduação Ciências Médicas: Psiquiatria, Department of Psychiatry and Forensic Medicine , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , Brasil. 7. g Department of Research , Nemours/Alfred I. duPont Hospital for Children , Wilmington , DE , USA. 8. h Department of Biological Sciences , University of Delaware , Newark , DE , USA. 9. i Department of Research , Instituto Nacional de Genética Médica Populacional-INAGEMP , Porto Alegre , Brasil. 10. j Department of Psychiatry , Núcleo de Formação Específica em Psiquiatria da Escola de Medicina da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brasil. 11. k Department of Psychiatry , Harvard Medical School , Boston , MA , USA.
Abstract
OBJECTIVES: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients. METHODS: All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele. RESULTS: In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders. CONCLUSIONS: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.
OBJECTIVES: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients. METHODS: All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele. RESULTS: In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders. CONCLUSIONS: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.
Authors: Nikolay Mehterov; Danail Minchev; Maria Gevezova; Victoria Sarafian; Michael Maes Journal: Mol Neurobiol Date: 2022-06-03 Impact factor: 5.682