Search

Studies have suggested Brain-Derived Neurotrophic Factors (BDNF) increase after electroconvulsive therapy (ECT) although they were methodologically limited and enrolled small sample sizes. We aimed at updating a systematic review and meta-analysis to explore BDNF changes after ECT for the treatment of depression. PubMed, PsycInfo, Embase and Global health were searched (March, 2021). Clinical trials that measured BDNF in the blood before and after ECT in adults (≥ 18 years old) with depression (major depressive disorder or bipolar disorder) were eligible. Data were pooled through random-effects meta-analyses. Twenty-eight studies involving 778 participants were included. Meta-analysis showed a significant increase in BDNF levels after ECT (Hedges' g = 0.28; 95% CI: 0.10, 0.46) while there was evidence of significant heterogeneity (I2 = 67.64%) but not publication bias/small-study effect. Subgroup analyses and meta-regressions were underpowered to detect significant differences. Meta-analysis of depression severity scores demonstrated a considerable larger treatment effect in reducing depressive symptoms after ECT (Hedge's g = −3.72 95% CI: −4.23, −3.21). This updated review showed that BDNF blood levels increased after ECT treatment. However, there was still evidence of substantial heterogeneity and there were limited sample sizes to investigate factors driving the variability of effects across studies. Importantly, the increase in BDNF levels was substantially smaller than the observed in depressive symptomatology, which could be indicative that the former was independent than the latter. Additional studies with larger sample sizes are currently required. [ABSTRACT FROM AUTHOR]

Synaptic plasticity and brain-derived neurotrophic factor (BDNF) signalling are proposed to play key roles in antidepressant drug action. Ketamine, an N-methyl-D-aspartate receptor antagonist and putative antidepressant, may increase synaptic plasticity in prefrontal cortex through higher expression of BDNF. Furthermore, ketamine was shown to change resting-state functional connectivity (RSFC) of dorsomedial prefrontal cortex (dmPFC). In a randomised, placebo-controlled study, we investigated acutely (100 min) and at 24 h following subanesthetic ketamine infusion which dmPFC seeded RSFC changes are most strongly associated with plasma BDNF level changes in 53 healthy participants (21 females, age: 24.4 ± 2.9 years) using 7 T-fMRI. We observed higher relative levels of BDNF 2 h and 24 h after ketamine compared to placebo. Whole-brain regression revealed that the change in BDNF after 24 h was associated with RSFC decreases from dmPFC to posterior cingulate cortex and ventromedial PFC at 24 h and exploratively also at the 100 min measurement point. Follow-up analyses revealed that RSFC reductions following ketamine were restricted to subjects showing increased BDNF levels at 24 h. Our findings indicate BDNF level dynamics following ketamine are related to acute and 24 h RSFC changes. Particularly when BDNF increases are observed after ketamine infusion, a disconnection from dmPFC after 24 h is seen and may reflect synaptic plasticity effects. [ABSTRACT FROM AUTHOR]

Objectives: Executive dysfunctions are frequently seen in patients with major depressive disorder (MDD) and normalise in many cases during effective antidepressant therapy. This study investigated whether a normalisation of executive dysfunctions during antidepressant treatment correlates with or can be predicted by clinical parameters or levels of brain-derived neurotrophic factor (BDNF). Methods: In 110 MDD patients with executive dysfunctions (percentile <16), executive functions and plasma BDNF levels were analysed at baseline, and days 14 and 56 of an antidepressant treatment. BDNF exon IV and P11 methylation status was studied at baseline. Results: Eighty patients (73%) experienced a normalisation of executive dysfunctions, while 30 (27%) suffered from persistent dysfunctions until day 56. Patients with persistent dysfunctions had significantly higher HAMD scores at days 14 and 56, and lower plasma BDNF levels at each time point than patients with a normalisation of dysfunctions (F1= 10.18; P = 0.002). This was seen for verbal fluency, but not processing speed. BDNF exon IV and p11 promoter methylation was not associated with test performance. Conclusions: Our results corroborate a concomitant amelioration of executive dysfunctions with successful antidepressant therapy and support a role of BDNF in the neural mechanisms underlying the normalisation of executive dysfunctions in MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96 [ABSTRACT FROM AUTHOR]

Objectives. Low serum BDNF levels have been found in depressed patients. No study has systematically investigated whether individual symptoms or symptom profiles within a depressed population contribute to low BDNF levels found in depressed subjects. Methods. All 1070 patients with a past 6-month diagnosis of major depressive disorder from the Netherlands Study of Depression and Anxiety (NESDA) were included. Composite International Diagnostic Interview (CIDI) and Inventory of Depressive Symptoms (IDS) items were tested individually in separate multiple regression analyses with serum BDNF level as the dependent and the CIDI or IDS item as independent variable. Subsequently, we compared BDNF levels between patients with seasonal affective disorder (based on the Seasonal Pattern Assessment Questionnaire) and melancholic depression, atypical depression and moderate depression (based on a latent class analysis). All analyses were adjusted for confounders. Results. Only one item was significantly associated with serum BDNF levels, namely the CIDI item 'loss of interest' (β = 0.14; P < 0.01). Counterintuitively the presence of this symptom was associated with higher BDNF levels. Other items and the comparison between different types of depression did not reveal significant differences. Conclusions. Decreased serum BDNF levels in depression cannot be attributed to a specific symptom or symptom cluster. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate whether electroconvulsive therapy (ECT), a very effective non-pharmacological treatment for mood disorders, induces neurotrophic effects, indexed by the measurement of peripheral brain-derived neurotrophic factor (BDNF) levels. Methods. Systematic review and meta-analysis of clinical trials published in PubMed/Medline from the first date available to October 2013. We included studies measuring pre- and post-BDNF blood levels under ECT in patients with mood disorders in the acute depressive episode. Results. Eleven studies ( n = 221 subjects) were eligible. These studies enrolled subjects with unipolar, bipolar and psychotic depression and varied regarding electrode placement (unipolar vs. bipolar) and previous use of pharmacotherapy. Nonetheless, BDNF significantly increased after ECT (Hedges' g pooled, random-effects model of 0.354; 95% CI = 0.162-0.546). The results were robust according to sensitivity analysis and Begg's funnel plot did not suggest publication bias. Meta-regression results did not show association of the outcome with any clinical and demographic variable, including depression improvement. Conclusions. Our meta-analysis indicates that, similar to pharmacological interventions, peripheral BDNF increases after ECT treatment. The lack of correlation between BDNF increasing and depression improvement suggests that ECT induces neurotrophic effects regardless of clinical response in depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]