Dataset Information

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

ABSTRACT:

Objective

Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy.

Method

A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis.

Results

The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ? 0.001) and decreased depressive symptoms (p ? 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008).

Conclusion

Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

SUBMITTER: Peters RB

PROVIDER: S-EPMC7861181 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

Peters Renata B RB Xavier Janaína J Mondin Thaíse C TC Cardoso Taiane de A TA Ferreira Fabiana B FB Teixeira Liana L Gräeff Kiane K Quevedo Luciana de A LA Jansen Karen K Souza Luciano D LD Oses Jean P JP Pinheiro Ricardo T RT da Silva Ricardo A RA Ghisleni Gabriele G

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 20200101 1

<h4>Objective</h4>Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy.<h4>Method</h4>A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamil ...[more]

PMID: 32844885

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Project description:Background:Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Methods:Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Results:Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. Conclusions:This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:BackgroundBrain-derived neurotrophic factor (BDNF) is a candidate for susceptibility locus of Panic disorder (PD). However, the findings about the role of the BDNF Val66Met variant in PD were not consistent. Till now, the relationship between BDNF Val66Met polymorphism and anxiety-related traits in PD patients has been rarely explored. This study aimed to explore the relationship among BDNF Val66Met polymorphism, plasma BDNF level and anxiety-related trait in Chinese PD patients.MethodThis multi-center study included 116 PD patients and 99 health controls. We detected single-nucleotide polymorphism (SNP) of BDNF rs6265 (Val66Met) and BDNF plasma level in the two groups. In addition, PD patients were administered the State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Rating Scale (HAMA-14). Quantitative comparison of the differences of BDNF concentration among subjects with different genotypes and association between BDNF Val66Met genotype and trait anxiety were performed.ResultsThere were no significant differences in the genotype frequency (p = 0.79) or allele frequency (p = 0.88) between PD patients and health controls. BDNF plasma levels of PD patients were significantly lower than those in control group (p = 0.003). BDNF plasma levels of the Met/Met genotype were significantly lower than those of Val/Met genotype in PD patients (p = 0.033). PD patients carried Met/Met genotype showed significantly higher scores in STAI trait compared to those carried Val/Val genotype (p = 0.045) and Val/Met genotype (p = 0.018). STAI trait scores of PD patients with agoraphobia were significantly higher than those of patients without agoraphobia (p < 0.05). The ANCOVA showed that the dependent variable STAI trait score was significantly affected by factor "genotype" (Val/Val, Val/Met, Met/Met, p = 0.029), and covariate "agoraphobia" (p = 0.008). In this model, 11.5% of the variance of the STAI trait score was explained by the BDNF genotype. Contrast analysis showed STAI trait scores of Met/Met subjects were significantly higher than those of Val/Met (p = 0.018) and Val/Val individuals (p = 0.045).ConclusionWe found that anxiety trait was associated with the BDNF polymorphism in PD patients. BDNF Met/Met genotype may decrease plasma BDNF level and increase trait anxiety in panic disorder.

Dataset Information

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

Objective

Method

Results

Conclusion

Publications

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

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