A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression

Sen, Srijan; Nesse, Randolph M.; Stoltenberg, Scott F.; Li, Sheng; Gleiberman, Lillian; Chakravarti, Aravinda; Weder, Alan B.; Burmeister, Margit

doi:10.1038/sj.npp.1300053

Cited by 311 publications

(250 citation statements)

References 32 publications

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“…In humans, decreased serum BDNF levels were reported recently in major depressed patients (Karege et al, 2002a) and increasing BDNF concentrations have been observed after antidepressant treatment (Shimizu et al, 2003). These data suggest BDNF concentrations to be a trait connected with depressed mood, which is also in line with the recent finding that a BDNF coding variant is associated with a depression-related personality trait in the NEO-FFI (Sen et al, 2003). The question as to whether this depression-related trait is also correlated to BDNF protein serum concentrations in healthy never-treated human volunteers has been addressed in this study.…”

Section: Introductionsupporting

confidence: 80%

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BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

Lang

Hellweg

Gallinat

2004

Neuropsychopharmacol

199

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The issue of neurotrophins is recognized as a new lead in the quest for a deeper understanding of mood disorders. This hypothesis has emerged from experimental evidence suggesting that antidepressant drugs might work by a neuroprotective effect through the stimulation of the neurotrophin expression in distinct regions of the CNS. Endogenous levels of BDNF protein were measured in the serum samples of 118 healthy unrelated volunteers (64 male, 54 female, age: 42.1713.0 years), and the NEO-FFI has been performed in all subjects. BDNF serum values amounted to 16.377.3 ng/ml. BDNF concentration correlated significantly with age (r ¼ 0.182, p ¼ 0.048), but showed no gender differences (male 16.177.2, female 16.577.4 ng/ml). A negative correlation between the BDNF serum concentration and the depression-related factor neuroticism (r ¼ À0.212, p ¼ 0.022) has been found. Low BDNF levels in healthy humans with depressive personality traits might constitute a risk marker, reflecting a personality profilethat is linked to vulnerability to mood disorders. These results provide further support for the hypothesis that BDNF may be central to the development of depressive mood states.

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Section: Introductionsupporting

confidence: 80%

“…finding that also a BDNF coding variant is associated with the NEO personality inventory domain neuroticism (Sen et al, 2003). Also, BDNF gene association studies showed that the BDNF locus confers susceptibility to bipolar disorder (Neves-Pereira et al, 2002;Sklar et al, 2002).…”

Section: Discussionmentioning

confidence: 92%

BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

Lang

Hellweg

Gallinat

2004

Neuropsychopharmacol

199

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“…[24][25][26][27][28][29] Further evidence implicating the BDNF locus' involvement in mood disorders arises from studies of neuroticism, a trait highly correlated with depression. [30][31][32][33] We have recently described an association between the BDNF (GT) n marker and a haplotype containing the Val 66 Met val allele with COMD in 93 case-control pairs. 34 Overall, substantial reason exists to further examine BDNF as a candidate gene for depressive disorders such as COMD.…”

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confidence: 99%

Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample

et al. 2005

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Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has been implicated in the neurobiology of depression. Our group has previously reported an association between a BDNF variant and childhood-onset mood disorder (COMD) in an adult sample from Pittsburgh. We hypothesize that variants at the BDNF locus are associated with COMD. Six BDNF polymorphisms were genotyped in 258 trios having juvenile probands with childhood-onset DSM-IV major depressive or dysthymic disorder. Keywords: neurotrophic factors; mood disorder; childhood-onset; genetic association; haplotype Mood disorders rank fourth among the most significant global public health problems. 1 The prevalence of the juvenile-onset subtype of depressive disorder increases dramatically across the years of childhood and adolescence, with an estimated lifetime prevalence close to 20% by late adolescence. 2 Juvenile-onset mood disorders are associated with serious morbidity, including recurrence, impaired interpersonal functioning, and increased risks of bipolar disorder and suicide. 2,3 The influence of hereditary factors on susceptibility to major depression has been documented based on twin and adoption studies. 4 Twin studies in youth have identified significant heritability for depressive symptoms. 5,6 It has also been proposed that genetic aspects of liability to mood disorder may be more readily identified in families of childhood-and adolescentonset probands. 7 Accordingly, first-degree relatives of childhood-onset mood disorder probands have higher rates of affective disorder than do first-degree relatives of adult-onset mood disorder probands. 8 Evidence from both preclinical and clinical studies implicates brain-derived neurotrophic factor (BDNF) in mood disorders. Altered BDNF expression in stress-related depression via cellular signalling has been described in animal models. Repeated antidepressant administration, including electroconvulsive seizures, is associated with increased hippocampal BDNF expression, neuronal plasticity and neurogenesis. 9-11 Human neuroimaging 12,13 post mortem 14 and clinical [15][16][17] investigations indirectly support the hypothesis that neurotrophic factors play a key role in depression. As well, human linkage studies in

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“…These findings suggest that the BDNF Val66Met polymorphism does not have a direct effect on AS. This finding is in line with studies that have found no significant direct association between BDNF Val66Met polymorphism and personality traits such as neuroticism or harm avoidance and anxiety disorders or mood disorders, including OCD, panic disorder, PTSD and depression (Arias et al, 2012; Chen et al, 2013; Frustaci et al, 2008; Hong et al, 2012; Minelli et al, 2011; Surtees et al, 2007; Terracciano et al, 2010), despite some studies reporting such associations (Frustaci et al, 2008; Lang et al, 2005; Min et al, 2013; Montag et al, 2010; Sen et al, 2003; Terracciano et al, 2010). Firstly, the grouping of Met66 allele carriers (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have reported associations between the BDNF Val66Met polymorphism and personality traits such as trait anxiety and neuroticism (Lang et al, 2005; Sen et al, 2003), while others have not (Terracciano et al, 2010; Willis-Owen et al, 2005). Previous studies have found associations between the Met66 allele and increased introversion (Terracciano et al, 2010), harm avoidance (Montag, Basten, Stelzel, Fiebach, & Reuter, 2010), tendency to ruminate (Beevers, Wells, & McGeary, 2009), lower levels of conscientiousness (Hiio et al, 2011), an increased vulnerability to stress (Casey et al, 2009), increased anxiety-related behaviours (Chen et al, 2006) and increased risk of an anxiety disorder in children and adolescents (Tocchetto et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample

Martin

Hemmings

Kidd

et al. 2018

European Journal of Psychotraumatology

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Background: Anxiety disorders in youth are attributable to multiple causal mechanisms, comprising biological vulnerabilities, such as genetics and temperament, and unfavourable environmental influences, such as childhood maltreatment (CM).Objective: A gene-environment (G x E) interaction study was conducted to determine the interactive effect of the BDNF Val66Met polymorphism and CM to increase susceptibility to anxiety sensitivity (AS) in a sample of mixed race adolescents.Method: Participants (n = 308, mean age = 15.8 years) who were all secondary school students and who completed measures for AS and CM were genotyped for the BDNF Val66Met polymorphism. Hierarchical multiple regression analysis was conducted to assess G x E influences on AS. Age and gender were included in the models as covariates as age was significantly associated with AS total score (p < .05), and females had significantly higher AS scores than males (p < .05).Results: A main effect of CM on AS was evident (p < .05), however, no main effect of BDNF genotype on AS was observed (p > .05). A non-significant G x E effect on AS was revealed (p < .05).Conclusions: Our results suggest that CM does not have a moderating role in the relationship between the BDNF Val66Met genotype and the increased risk of anxiety-related phenotypes, such as AS. Given the exploratory nature of this study, findings require replication in larger samples and adjustment for population stratification to further explore the role of BDNF Val66Met and CM on AS in mixed race adolescents.

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A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression

Cited by 311 publications

References 32 publications

BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample

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