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Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms.

ABSTRACT: BDNF Val66Met by chronic stress interaction has been studied using childhood stress as a moderator, but has not been widely studied using chronic stress in adulthood.Two independent samples were used: Duke-CG (238 Caucasians) and MESA (5524 Caucasians, African Americans and Hispanics). Chronic stress in Duke-CG was operationalized as having primary caregiving responsibility for a spouse or relative with diagnosed Alzheimer's disease or other major dementia; chronic stress in MESA was defined using chronic burden score constructed from self-reported problems of health (self and someone close), job, finance and relationships. CES-D scale was the measure of depression in both samples. The BDNF Val66Met by adulthood chronic stress interaction predicting CES-D was examined using linear regression, adjusted for covariates.The main effect of BDNF Val66Met genotype on CES-D scores was non-significant (ps > 0.607) but the adulthood chronic stress indicator was significant (ps < 0.001) in both samples. The BDNF Val66Met genotype by adulthood chronic stress interaction was also significant (ps < 0.039) in both samples. The impact of chronic stress in adulthood on CES-D scores was significantly larger in Val/Val genotype individuals than Met carriers.We found in two independent samples that depression levels increased significantly more as a function of adulthood chronic stress Val/Val genotype carriers than Met carriers. Individuals with the Val/Val genotype and chronic stress exposure could be targeted for interventions designed to reduce risk of depression if this finding is confirmed in future studies.

SUBMITTER: Jiang R

PROVIDER: S-EPMC3605893 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms.

Jiang Rong R Brummett Beverly H BH Babyak Michael A MA Siegler Ilene C IC Williams Redford B RB

Journal of psychiatric research 20121108 2

<h4>Background</h4>BDNF Val66Met by chronic stress interaction has been studied using childhood stress as a moderator, but has not been widely studied using chronic stress in adulthood.<h4>Methods</h4>Two independent samples were used: Duke-CG (238 Caucasians) and MESA (5524 Caucasians, African Americans and Hispanics). Chronic stress in Duke-CG was operationalized as having primary caregiving responsibility for a spouse or relative with diagnosed Alzheimer's disease or other major dementia; chr ...[more]

PMID: 23140671

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Project description:BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

Project description:The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients.The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures.Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger.The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.

Dataset Information

Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms.

Publications

Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms.

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