The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met

Contains fulltext : 98431.pdf (publisher's version ) (Open Access)RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele. METHODS: We investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val(66)Met polymorphism. RESULTS: Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val(66)Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety. CONCLUSIONS: These gene-environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events

Serum brain-derived neurotrophic factor: Determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is involved in major depressive disorder and neurodegenerative diseases. Clinical studies, showing decreased serum BDNF levels, are difficult to interpret due to limited knowledge of potential confounders and mixed results for age and sex effects. We explored potential determinants of serum BDNF levels in a community sample of 1230 subjects. METHODS: Multiple linear regression analyses with serum BDNF level as the dependent variable were conducted to explore the effect of four categories of potential BDNF determinants (sampling characteristics, sociodemographic variables, lifestyle factors and somatic diseases) and of self-reported depressive symptoms (Beck's Depression Inventory (BDI). RESULTS: Our results show that BDNF levels decline with age in women, whereas in men levels remain stable. Moreover, after controlling for age and gender, the assays still showed lower serum BDNF levels with higher BDI sum scores. Effects remained significant after correction for two main confounders (time of sampling and smoking), suggesting that they serve as molecular trait factors independent of lifestyle factors. CONCLUSIONS: Given the age-sex interaction on serum BDNF levels and the known association between BDNF and gonadal hormones, research is warranted to delineate the effects of the latter interaction on the risk of psychiatric and neurodegenerative diseases

Serum BDNF Concentrations Show Strong Seasonal Variation and Correlations with the Amount of Ambient Sunlight

Contains fulltext : 109494.pdf (publisher's version ) (Open Access)Earlier findings show seasonality in processes and behaviors such as brain plasticity and depression that in part are regulated by Brain-Derived Neurotrophic Factor (BDNF). Based on this we investigated seasonal variation in serum BDNF concentrations in 2,851 persons who took part in the Netherlands Study of Depression and Anxiety (NESDA). Analyses by month of sampling (monthly n's >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001) with increasing concentrations in the spring-summer period (standardized regression weight (ss) = 0.19, P<.0001) and decreasing concentrations in the autumn-winter period (ss = -0.17, P<.0001). Effect sizes [Cohen's d] ranged from 0.27 to 0.66 for monthly significant differences. We found similar seasonal variation for both sexes and for persons with a DSM-IV depression diagnosis and healthy control subjects. In explorative analyses we found that the number of sunshine hours (a major trigger to entrain seasonality) in the week of blood withdrawal and the 10 weeks prior to this event positively correlated with serum BDNF concentrations (Pearson's correlation coefficients ranged: 0.05-0.18) and this could partly explain the observed monthly variation. These results provide strong evidence that serum BDNF concentrations systematically vary over the year. This finding is important for our understanding of those factors that regulate BDNF expression and may provide novel avenues to understand seasonal dependent changes in behavior and illness such as depression. Finally, the findings reported here should be taken into account when designing and interpreting studies on BDNF

Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety

Objectives. Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compared to healthy controls. We further examined the associations of gender and some of the clinical characteristics of anxiety with BDNF levels. Methods. Serum BDNF levels were determined in 393 unmedicated, non-depressed patients with social anxiety disorder, panic disorder, agoraphobia, and generalised anxiety disorder (66.7% females) and in 382 healthy controls (62.0% females). Results. Overall, there were no differences in BDNF levels among patients and controls, regardless of type of anxiety disorder. Analyses stratified by gender revealed that female patients had lower levels of BDNF relative to female controls (P 1 anxiety disorder (P <0.01, d = 0.32). BDNF levels were similar among male patients and controls and unrelated to the clinical characteristics of anxiety. Conclusion. Our results mirror preclinical findings indicating that gender plays a role in the association between BDNF and anxiety and suggest that BDNF might play a role in the pathophysiology of anxiety in women

Descriptive information on the NESDA sample (mean ± std or percentages [<i>n</i>]) by season of sampling.

<p>Abbreviations: BAI, Beck’s Anxiety Inventory; IDS, Inventory of Depressive Symptoms; MDD, Major Depressive Disorder.</p><p>1 Mean met-minutes (i.e., ratio of energy expenditure during activity to energy expenditure at rest).</p><p>2 Current (6 months diagnosis).</p><p>3 Included a diagnosis of social phobia, panic disorder, generalized anxiety disorder, and/or agoraphobia.</p><p>4 Included the use of a pharmacological antidepressant (SSRI, SNRI, TCA, NaSSA, and/or St. John’s worth) for at.</p><p>least one month at regular dose (World Health Organization [WHO]).</p><p>a Post-hoc tests showed higher levels in the winter as compared to the other seasons.</p><p>b Post-hoc tests showed higher percentages in the summer, autumn and spring as compared to the winter season.</p

Serum BDNF concentrations by month of sampling and gender (Panel A) and current psychiatric status (Panel B).

<p>Error bars reflect the SEM.</p

Serum BDNF concentrations by month of sampling.

<p>Error bars reflect the SEM. For pair-wise comparisons we refer to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048046#pone.0048046.s004" target="_blank">Table S2</a>.</p