The BDNF Val66Met polymorphism and anxiety: Support for animal knock-in studies from a genetic association study in humans

Montag, Christian; Basten, Ulrike; Stelzel, Christine; Fiebach, Christian J.; Reuter, Martin

doi:10.1016/j.psychres.2008.08.005

Cited by 109 publications

(83 citation statements)

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“…These findings, in conjunction with BDNF polymorphisms having strong association in the literature with synaptic plasticity (Martinowich and Lu 2008) and mood disorders (Montag et al. 2010) imply an association with increased risk of PTSD.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…BDNF has also been implicated in amygdaladependent fear conditioning in rodents (Monfils et al, 2009). Moreover, variations in this polymorphism have been associated with anxiety-related traits in humans (Montag et al, 2010). BDNF is therefore a likely candidate to play a role in fear conditioning and generalization as well.…”

Section: Genetic Factorsmentioning

confidence: 99%

Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research

et al. 2015

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Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

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“…The Met allele has been associated with lower serum BDNF (Ozan et al, 2010), though this has not been consistently replicated (Duncan et al, 2009;Terracciano et al, 2010;Zhou et al, 2011). The Met allele has also been associated with increased suicide risk (Kanellopoulos et al, 2011;Pregelj et al, 2011;Sarchiapone et al, 2008), various depression-related traits (Beevers et al, 2009;Gatt et al, 2008;Gatt et al, 2010;Hayden et al, 2010;Jiang et al, 2005;Lau et al, 2010;Montag et al, 2010;Montag et al, 2008;Montag et al, 2009), and occasionally, a depression diagnosis (Aguilera et al, 2009;Borroni et al, 2009;Kim et al, 2008;Lavebratt et al, 2010). However, there are multiple studies in which this association with depression has not been replicated Figueira et al, 2010;Middeldorp et al, 2010;Ribeiro et al, 2007;Suchanek et al, 2011;Wray et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Lotrich

Albusaysi

Ferrell

2012

Neuropsychopharmacol

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Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brainderived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression. We therefore prospectively employed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Montgomery-Asberg Depression Rating Scale (MADRS) in 124 initially euthymic patients during treatment with interferon-alpha (IFN-a), assessing serum BDNF and rs6265. Using mixed-effect repeated measures, lower pretreatment BDNF was associated with higher depression symptoms during IFN-a treatment (F 144,17.2 ¼ 6.8; Po0.0001). However, although the Met allele was associated with lower BDNF levels (F 1,83.0 ¼ 5.0; P ¼ 0.03), it was only associated with increased MADRS scores (F 4,8.9 ¼ 20.3; Po0.001), and not the BDI-II or HADS. An exploratory comparison of individual BDI-II items indicated that the Met allele was associated with suicidal ideation, sadness, and worthlessness, but not neurovegetative symptoms. Conversely, the serotonin transporter promoter polymorphism (5-HTTLPR) short allele was associated with neurovegetative symptoms such as insomnia, poor appetite and fatigue, but not sadness, worthlessness, or suicidal ideation. IFN-a therapy further lowered BDNF serum levels (F 4,37.7 ¼ 5.0; P ¼ 0.003), but this decrease occurred regardless of depression development. The findings thus do not support the hypothesis that decreasing BDNF is the primary pathway by which IFN-a worsens depression. Nonetheless, the results support the hypothesis that BDNF levels influence resiliency against developing inflammatory cytokine-associated depression, and specifically to a subset of symptoms distinct from those influenced by 5-HTTLPR. Neuropsychopharmacology (2013) 38, 985-995;

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The BDNF Val66Met polymorphism and anxiety: Support for animal knock-in studies from a genetic association study in humans

Cited by 109 publications

References 44 publications

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

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

Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

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