Brain derived neurotrophic factor (<i>BDNF</i>) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence

Zhang, Huiping; Özbay, Fatih; Lappalainen, Jaakko; Kranzler, Henry R.; Dyck, Christopher H. van; Charney, Dennis S.; Price, Lawrence H.; Southwick, Steven M.; Yang, Bao‐Zhu; Rasmussen, Ann Marie; Gelernter, Joel

doi:10.1002/ajmg.b.30332

Cited by 179 publications

(146 citation statements)

References 47 publications

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“…11,19,21,33,34,36,37,40,42,43 Statistical analysis The meta-analysis examined the allelic association of the Met allele with the risk of MDD relative to the Val allele (OR Met versus Val). Besides this, genotypic ORs were calculated for the heterozygous Val/Met and homozygous Met/Met genotypes separately, with the Val/Val genotype as the reference.…”

Section: Data Extractionmentioning

confidence: 99%

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

et al. 2008

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Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR MET , 95% CI; 1.27 (1.10-1.47); OR MET/MET , 95% CI; 1.67 (1.19-2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest.

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Section: Data Extractionmentioning

confidence: 99%

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

et al. 2008

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“…2006). BDNF has a role in activity‐dependent neural plasticity processes of the hippocampus and amygdala, implicated in long‐term learning and memory (Hariri et al.…”

Section: Introductionmentioning

confidence: 99%

Brain‐derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress

et al. 2015

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BackgroundIn addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment.MethodsBoth pre‐ and postdeployment data on 231 of 458 soldiers were analyzed. Postdeployment assessments occurred within 30 days from returning stateside and included a battery of psychological health, medical history, and demographic questionnaires; neurocognitive tests; and blood serum for the D2 dopamine receptor (DRD2), apolipoprotein E (APOE), and brain‐derived neurotropic factor (BDNF) genes.ResultsSoldiers who screened positive for traumatic stress at postdeployment had significantly higher scores in depression (d = 1.91), anxiety (d = 1.61), poor sleep quality (d = 0.92), postconcussion symptoms (d = 2.21), alcohol use (d = 0.63), traumatic life events (d = 0.42), and combat exposure (d = 0.91). BDNF Val66 Met genotype was significantly associated with risk for sustaining a mild traumatic brain injury (mTBI) and screening positive for traumatic stress. Predeployment traumatic stress, greater combat exposure and sustaining an mTBI while deployed, and the BDNF Met/Met genotype accounted for 22% of the variance of postdeployment PTSD scores (R 2 = 0.22, P < 0.001). However, predeployment traumatic stress, alone, accounted for 17% of the postdeployment PTSD scores.ConclusionThese findings suggest predeployment traumatic stress, genetic, and environmental factors have unique contributions to the development of combat‐related traumatic stress in military service members.

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“…Considering its pivotal role in neurodevelopment and adaptation, the variant has also received considerable attention as a candidate gene locus for mental disorder and treatment response (Martinowich et al, 2007). Among others, BDNF Val 66 Met has previously been implicated as genetic risk factor for bipolar disorder (Sklar et al, 2002), schizophrenia (Neves-Pereira et al, 2005), and depression (Verhagen et al, 2010), although the validity of the disease associations is subject to much debate (Zhang et al, 2006). …”

Section: Introductionmentioning

confidence: 99%

Effects of the BDNF Val66Met Polymorphism on White Matter Microstructure in Healthy Adults

Tost

Alam

Geramita

et al. 2012

Neuropsychopharmacol

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The BDNF Val 66 Met polymorphism, a possible risk variant for mental disorders, is a potent modulator of neural plasticity in humans and has been linked to deficits in gray matter structure, function, and cognition. The impact of the variant on brain white matter structure, however, is controversial and remains poorly understood. Here, we used diffusion tensor imaging to examine the effects of BDNF Val 66 Met genotype on white matter microstructure in a sample of 85 healthy Caucasian adults. We demonstrate decreases of fractional anisotropy and widespread increases in radial diffusivity in Val/Val homozygotes compared with Met-allele carriers, particularly in prefrontal and occipital pathways. These data provide an independent confirmation of prior imaging genetics work, are consistent with complex effects of the BDNF Val 66 Met polymorphism on human brain structure, and may serve to generate hypotheses about variation in white matter microstructure in mental disorders associated with this variant.

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Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence

Cited by 179 publications

References 47 publications

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

Brain‐derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress

Effects of the BDNF Val66Met Polymorphism on White Matter Microstructure in Healthy Adults

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