Plasma Brain-derived Neurotrophic Factor Research Articles

Effects of antidepressant and antipsychotic medication on peripheral brain-derived neurotrophic factor concentration: Systematic review and meta-analysis

Brain-derived neurotrophic factor (BDNF) is an important regulatory protein in the pathophysiology of psychiatric disorders. Several studies have reported the relationship between peripheral BDNF concentrations and the use of psychoactive drugs. However, the results remain controversial. This study aimed to evaluate the effects of psychoactive drugs on BDNF concentrations and to explore the association between changes in BDNF concentrations and improvements in clinical scores. A systematic review and meta-analysis were conducted. Six electronic databases, including PubMed, Scopus, Medline, Web of Science, Google Scholar and Science Direct, were searched. Changes in BDNF concentrations were compared before and after psychoactive treatment, using the standardized mean difference (SMD) and 95 % confidence interval (95 % CI). Twenty-three studies were included. A significant increase in serum BDNF concentrations was observed after treatment with antipsychotics (SMD=0.43; 95 %CI: 0.26, 0.60) and antidepressants (SMD=0.49; 95 %CI: 0.23, 0.74). However, the plasma BDNF concentration was not affected by antidepressant and antipsychotic medication. Although an improvement in clinical scores was observed after treatment, no significant association was observed between changes in BDNF concentrations and the changes in the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAM-D) scores. In conclusion, antidepressants and antipsychotics increase serum BDNF concentrations.

Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: an investigation using Mendelian randomisation

BackgroundAltered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders. ObjectiveTo investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study. MethodsWe selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders). ResultsWe observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95% confidence interval [CI]: 0.774-0.958, P = 0.006, PFDR = 0.078), epilepsy (OR = 0.927, 95% CI: 0.880-0.976, P = 0.004, PFDR = 0.078), focal epilepsy (OR = 0.928, 95% CI: 0.874–0.986, P = 0.016, PFDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95% CI: 0.964–0.999, P = 0.041, PFDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95% CI: 0.81-0.96, P < 0.01). The combined analysis of three consortium datasets demonstrated a considerable impact of plasma BDNF on epilepsy (OR = 0.94, 95% CI: 0.90-0.98, P < 0.01) and a suggestive impact on focal epilepsy (OR = 0.94, 95% CI: 0.89-0.99, P = 0.02). However, there was no apparent correlation between plasma BDNF levels and other neurological disorders or related subtypes. ConclusionsOur study supports a possible causal relationship between elevated plasma BDNF levels and a reduced risk of nITH, epilepsy, and focal epilepsy.

Expression Patterns of miRNAs in Egyptian Children with ADHD: Clinical Study with Correlation Analysis

ADHD has huge knowledge gaps concerning its etiology. MicroRNAs (miRNAs) provide promising diagnostic biomarkers of human pathophysiology and may be a novel therapeutic option. The aim was to investigate the levels of miR-34c-3p, miR-155, miR-138-1, miR-296-5p, and plasma brain-derived neurotrophic factor (BDNF) in a group of children with ADHD compared to neurotypicals and to explore correlations between these measures and some clinical data. The participants were children with ADHD in Group I (N = 41; age: 8.2 ± 2) and neurotypical ones in Group II (N = 40; age: 8.6 ± 2.5). Group I was subjected to clinical examination, the Stanford Binet intelligence scale-5, the preschool language scale, and Conner’s parent rating scale-R. Measuring the expression levels of the miRNAs was performed by qRT-PCR for all participants. The BDNF level was measured by ELISA. The lowest scores on the IQ subtest were knowledge and working memory. No discrepancies were noticed between the receptive and expressive language ages. The highest scores on the Conner’s scale were those for cognitive problems. Participants with ADHD exhibited higher plasma BDNF levels compared to controls (p = 0.0003). Expression patterns of only miR-34c-3p and miR-138-1 were downregulated with significant statistical differences (p˂0.01). However, expression levels of miR-296-5p showed negative correlation with the total scores of IQ (p = 0.03). MiR-34c-3p, miR-138-1, while BDNF showed good diagnostic potential. The downregulated levels of miR-34c-3p and miR-138-1, together with high BDNF levels, are suggested to be involved in the etiology of ADHD in Egyptian children. Gender differences influenced the expression patterns of miRNAs only in children with ADHD.

Plasma and Platelet Brain-Derived Neurotrophic Factor (BDNF) Levels in Bipolar Disorder Patients with Post-Traumatic Stress Disorder (PTSD) or in a Major Depressive Episode Compared to Healthy Controls.

Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD (n = 20) or in a major depressive episode (n = 20) were rigorously recruited together with unrelated healthy controls (n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets' role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients.

An analysis of the relationship of "the Mozart effect" with BDNF levels in anatomy education.

In 1993, an increase was observed in the spatial IQ scores of the volunteers who listened to Mozart's sonata K448 for 10 min, and this phenomenon entered the literature as the "Mozart effect." Other studies have shown that this effect is particularly evident in spatial skill tests. A large body of research has provided evidence that spatial ability is associated with success in learning anatomy. In this study, Kastamonu University Faculty of Medicine students were divided into two groups during 16-h practical training spanning 30 days. While one of the groups listened to Mozart's K448 sonata as the background music in all lessons, the control group attended the lessons in their standard form. At the end of each lesson, all students solved a modified mental rotation test including questions involving anatomical structures. Before starting the study, after the first laboratory class, on the 15th and 30th day of the study, blood samples were taken from the participants, and plasma brain-derived neurotrophic factor (BDNF) levels were determined. The effect of time on mental rotation score and plasma BDNF level was significant (p < 0.001 for both). The effect of group was also significant (p < 0.001 for both). Pairwise comparisons showed significance in the fifth, sixth, seventh, and eighth mental rotation test (p < 0.001, p = 0.041, p < 0.001, p < 0.001, respectively) and in the third (Day 15) and fourth (Day 30) BDNF measurement (p < 0.001 for both). Our findings may indicate that specific background music may be useful for anatomy teaching.

How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

Salivary Brain-Derived Neurotrophic Factor and Cortisol Associated with Psychological Alterations in University Students.

Recent evidence reported mental health issues in university students such as anxiety and depressive symptoms and poor sleep quality. Decreased plasma brain-derived neurotrophic factor (BDNF) levels have been proposed as a biomarker of depressive symptoms, whereas cortisol levels are an index of energy mobilization and stress and have been linked to sleep quality. Given that salivary biomarkers represent an interesting new field of research, the aim of this cross-sectional study was to evaluate salivary BDNF and cortisol levels in university students to assess whether they have associations with psychological disturbances such as anxiety and depressive symptoms, sleep quality, and stress level. Salivary BDNF and cortisol levels were measured by specific immunoassays in 70 students whose mental health was also evaluated on the same day through the evaluation of anxiety and depression symptoms (Goldberg scale), sleep quality (Pittsburg Sleep Quality Index and Athens Insomnia Scale), and stress (self-perceived stress scale) and healthy lifestyle habits (alcohol consumption, smoking, regular exercise, and body mass index) were also measured. Multivariate regression analyses were performed in order to identify the strengths of associations between psychological alterations and the concentrations of BDNF, cortisol, and other variables. Salivary BDNF levels were significantly higher in students with more depressive symptoms, whereas no significant differences were found for cortisol levels. When performing the binary logistic regression model, BDNF levels are included as a predictor variable for a high-depressive-symptoms burden (p < 0.05). Students with worse sleep quality on the Pittsburg Scale had higher cortisol levels (p < 0.05). The subdomains of sleep latency and sleep medication were those significantly associated with salivary cortisol levels in logistic regression analyses (OR = 15.150, p = 0.028). Sleep medication only appeared to be related to cortisol levels (OR = 185.142, p = 0.019). Perceived stress levels and anxiety symptoms were not associated with BDNF or cortisol levels. BDNF could play a key role in the pathophysiology of mood-related disorders, and elevation of its peripheral levels could contribute to protecting neurons from the development of mental illness. Higher salivary cortisol levels measured in the morning are accompanied by poorer sleep quality. More research is needed, focusing on salivary biomarkers of disorders related to depressive symptoms and poor sleep quality as a potential tool for the diagnosis and prevention of mental illness.

Association between Brain-Derived Neurotrophic Factor and Lipid Profiles in Acute Ischemic Stroke Patients.

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55-90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187-3.051) for TG/HDL-C, 1.975 (95% CI: 1.188-3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113-3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003-1.030) and 0.926 (95% CI: 0.876-0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations.

Peripheral Levels of the Brain-Derived Neurotrophic Factor in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls. We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted using R version 4.0.4. The final analysis comprised 12 investigations covering 1422 CHD cases and 929 controls with mean ages of 59.66±13.56 and 53.78±13.61 years, respectively. The initial analyses revealed a tendency toward low levels of BDNF in the CHD group compared with the control group (SMD= -0.41; 95% CI, -1.12 to 0.30; P=0.26). After the removal of outliers, the difference achieved statistical difference (SMD= -0.56; 95% CI, -0.93 to -0.19; P<0.01). Subgroup analysis demonstrated no significant difference between serum and plasma BDNF levels (P=0.54); however, subgroup analyses of studies investigating plasma BDNF showed that patients with CHD had significantly lower BDNF levels. Serum and plasma BDNF concentrations were considerably lower in patients with CHD than in healthy controls. Further studies of higher quality are required on the potential role of BDNF as a biomarker of CHD pathophysiology and severity.

Brain-Derived neurotrophic factor and inflammatory biomarkers are unaffected by acute and chronic intermittent hypoxic-hyperoxic exposure in geriatric patients: a randomized controlled trial

Background Animal and human studies have shown that exposure to hypoxia can increase brain-derived neurotrophic factor (BDNF) protein transcription and reduce systematic inflammatory cytokine response. Therefore, the aim of this study was to investigate the acute and chronic effects of intermittent hypoxic-hyperoxic exposure (IHHE) prior to aerobic exercise on BDNF, interleukin-6 (IL-6), and C-reactive protein (CRP) blood levels in geriatric patients. Patients and Methods Twenty-five geriatric patients (83.1 ± 5.0 yrs, 71.1 ± 10.0 kg, 1.8 ± 0.9 m) participated in a placebo-controlled, single-blinded trial and were randomly assigned to either an intervention (IG) or control group (CG) performing an aerobic cycling training (17 sessions, 20 min·session−1, 3 sessions·week−1). Prior to aerobic cycling exercise, the IG was additionally exposed to IHHE for 30 min, whereas the CG received continuous normoxic air. Blood samples were taken immediately before (pre-exercise) and 10 min (post-exercise) after the first session as well as 48 h (post-training) after the last session to determine serum (BDNFS) and plasma BDNF (BDNFP), IL-6, and CRP levels. Intervention effects were analyzed using a 2 x 2 analysis of covariance with repeated measures. Results were interpreted based on effect sizes with a medium effect considered as meaningful (ηp 2 ≥ 0.06, d ≥ 0.5). Results CRP was moderately higher (d = 0.51) in the CG compared to the IG at baseline. IHHE had no acute effect on BDNFS (ηp 2 = 0.01), BDNFP (ηp 2 < 0.01), BDNF serum/plasma-ratio (ηp 2 < 0.01), IL-6 (ηp 2 < 0.01), or CRP (ηp 2 = 0.04). After the 6-week intervention, an interaction was found for BDNF serum/plasma-ratio (ηp 2 = 0.06) but not for BDNFS (ηp 2 = 0.04), BDNFP (ηp 2 < 0.01), IL-6 (ηp 2 < 0.01), or CRP (ηp 2 < 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training (d = 0.67) in the CG compared to the IG (d = 0.51). A main effect of time was found for BDNFP (ηp 2 = 0.09) but not for BDNFS (ηp 2 = 0.02). Within-group post-hoc analyses revealed a training-related reduction in BDNFP in the IG and CG by 46.1% (d = 0.73) and 24.7% (d = 0.57), respectively. Conclusion The addition of 30 min IHHE prior to 20 min aerobic cycling seems not to be effective to increase BDNFS and BDNFP or to reduce IL-6 and CRP levels in geriatric patients after a 6-week intervention. The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130).

Effect of mindfulness-based cognitive therapy vs. psychoeducational intervention on plasma brain-derived neurotrophic factor and cognitive function in bipolar patients: a randomized controlled trial.

Few controlled trials have assessed the benefits of Mindfulness Based Cognitive Therapy (MBCT) on cognitive functions and brain-derived neurotrophic factor (BDNF) in bipolar disorder (BD). This study aims to evaluate the impact of MBCT adjunctive treatment on these variables. Main hypothesis was that MBCT would improve cognitive functioning and BDNF more than Psychoeducation and TAU. Randomized, multicenter, prospective and single-blinded trial. Included BD outpatients randomly assigned to three treatment arms: MBCT plus treatment as usual (TAU), Psychoeducation plus Tau and TAU. Cognitive functions were assessed with Continuous Performance Test-III, Stroop Test, Trail Making Test, Digit Span and Letter-Number Sequencing from Wechsler Adult Intelligence Scale III, Face Emotion Identification Task and Face Emotion Discrimination Task. BDNF serum level was measured with ELISA. Patients were assessed at baseline, 8 weeks and 6 months. Eighty-four patients were recruited (TAU = 10, Psychoeducation = 34, MBCT = 40). No significant differences between treatment groups were found. MBCT does not achieve better results than Psychoeducation or TAU. Being Psychoeducation and TAU efficient interventions, as well as the scarce duration of a more complex intervention, such as MBCT, are suggested as explanatory variables of these results. ClinicalTrials.gov: NCT02133170. Registered 04/30/2014.

An Open-label Exploratory Study Investigating BDNF Essentials® on Cognition in Healthy Adults with Self-reported Memory Complaints

Background:: An open-label, exploratory study has been conducted to investigate the ef-ficacy of BDNF Essentials® for cognitive function and neurological health. Methods:: Twenty healthy adults ≥45 years of age, with a score ≥24 on the Mini-Mental State Ex-amination (MMSE-2) and self-reported memory complaints were supplemented with BDNF Es-sentials® for 84 days. Computerized Mental Performance Assessment System (COMPASS) tests for memory, attention, and processing speed were conducted, and change in plasma brain-derived neurotrophic factor (BDNF), Profile of Mood States (POMS), the Healthy People Sleep Quality Index (HPSQI), perceived stress scale (PSS), and salivary cortisol, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were assessed at baseline and days 28, 56, and 84. Results:: Supplementation with BDNF Essentials® significantly increased COMPASS tests for memory, attention, and processing speed (all P&lt;0.05). Salivary cortisol was found to be signifi-cantly decreased at days 56 and 84, and IL-6 at day 84 (P&lt;0.05). A reduction in depression-dejection at day 56 and in confusion-bewilderment at day 84, and an improvement in sleep satis-faction at day 56 (all p&lt;0.05) were reported. Conclusion:: BDNF Essentials® improved reaction time in measures of working memory, episodic memory, and attention, reduced biomarkers of stress and inflammation, and improved mood and sleep. BDNF Essentials® has been found to be safe and well-tolerated in adults with self-reported memory complaints.

Altered in vivo early neurogenesis traits in patients with depression: Evidence from neuron-derived extracellular vesicles and electroconvulsive therapy

BackgroundThe neurogenesis hypothesis is a promising candidate etiologic hypothesis for depression, and it is associated with electroconvulsive therapy (ECT). However, human in vivo molecular-level evidence is lacking. ObjectiveWe used neuron-derived extracellular vesicles (NDEVs) as a “window to the neurons” to explore the in vivo neurogenesis status associated with ECT in patients with treatment-resistant depression (TRD). MethodsIn this study, we enrolled 40 patients with TRD and 35 healthy controls (HCs). We isolated NDEVs from the plasma of each participant to test the levels of doublecortin (DCX), a marker of neurogenesis, and cluster of differentiation (CD) 81, a marker of EVs. We also assessed the plasma levels of brain-derived neurotrophic factor (BDNF), a protein that is known to be associated with ECT and neuroplastic processes. ResultsOur findings indicated that both the levels of DCX in NDEVs and BDNF in plasma were significantly lower in TRD patients compared to HCs at baseline, but increased following ECTs. Conversely, levels of CD81 in NDEVs were found higher in TRD patients at baseline, but did not change after the ECT treatments. Exploratory analyses revealed that lower levels of BDNF in plasma and DCX in NDEVs, along with higher CD81 levels in NDEVs, were associated with more severe depressive symptoms and reduced cognitive function at baseline. Furthermore, higher baseline CD81 concentrations in NDEVs were correlated with greater decreases in depression symptoms. ConclusionsWe first present human in vivo evidence of early neurogenesis using DCX through NDEVs: decreased in TRD patients, increased after ECTs.

Association between plasma brain-derived neurotrophic factor level and Alzheimer's disease: a Mendelian randomization study.

High brain-derived neurotrophic factor (BDNF) concentrations have been found to be associated with a decreased risk of Alzheimer's disease (AD) in observational studies, but the causality for this association remains unclear. Therefore, we aimed to examine the association between genetically determined plasma BDNF levels and AD using a two-sample Mendelian randomization (MR) method. Twenty single-nucleotide polymorphisms associated with plasma BDNF concentrations were identified as genetic instruments based on a genome-wide association study with 3301 European individuals. Summary-level data on AD were obtained from the International Genomics of Alzheimer's Project, involving 21,982 AD cases and 41,944 controls of European ancestry. To evaluate the relationship between plasma BDNF concentrations and AD, we employed the inverse-variance weighted method along with a series of sensitivity analyses. The inverse-variance weighted MR analysis showed that genetically determined BDNF concentrations were associated with a decreased risk of AD (odds ratio per SD increase, 0.91; 95% confidence interval, 0.86-0.96; p =0.001). The association between plasma BDNF concentrations and AD was further confirmed through sensitivity analyses using different MR methods, and MR-Egger regression suggested no directional pleiotropy for this association. Genetically determined BDNF levels were associated with a decreased risk of AD, suggesting that BDNF was implicated in the development of AD and might be a promising target for the prevention of AD.

Centella asiatica (Indian Pennywort) Extract and Exercise Increase Brain-Derived Neurotrophic Factor Plasma, Cognition, and Physical Fitness among Menopausal Women

Centella asiatica (Indian Pennywort) Extract and Exercise Increase Brain-Derived Neurotrophic Factor Plasma, Cognition, and Physical Fitness among Menopausal Women

The association of benzodiazepine and benzodiazepine-related drugs with outcomes after surgery for colorectal cancer

Benzodiazepines increase plasma brain-derived neurotrophic factor (BDNF) level which, in turn, may improve survival in colorectal cancer (CRC) patients. This study aimed to evaluate the associations between benzodiazepine and benzodiazepine-related drugs (BZRD) use and outcomes of patients operated for CRC. This is a retrospective cohort study including patients operated for CRC at Limoges’ University Hospital between 2010 and 2019. Data were collected from two sources: medical records of patients in the digestive, general and endocrine surgery department at Limoges University Hospital and from the Haute-Vienne general cancer registry. Patients were divided into benzodiazepine users and non-users. Outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 504 patients who underwent surgery for CRC, 125 (24.8%) patients were treated with benzodiazepine/BZRD drugs. Users and non-users of benzodiazepine/BZRD showed no statistically significant differences in 5-year OS (45.5 ± 1.9% vs. 46.5 ± 1.1% p = 0.25) and 5-year RFS (41.0 ± 2.1% vs. 39.6 ± 1.3%, p = 0.94), even after adjustment for confounders and propensity score (OS: aHR=1.02, 95%CI: 0.71–1.48; RFS: aHR=1.00, 95%CI: 0.72–1.40). Subgroup analysis on CRC patients with psychiatric disorders revealed that benzodiazepine users had better RFS (aHR=0.58, 95%CI: 0.35–0.96) compared with non-users, particularly, patients with stages III or IV of CRC had better OS (aHR=0.27; 95%CI: 0.12–0.59) and RFS (aHR=0.30, 95%CI: 0.15–0.62). OS and RFS was significantly better in patients taking benzodiazepines classified as anxiolytics, having longer half-life, and producing active metabolites. In conclusion, benzodiazepine use was not associated with outcomes in CRC patients. Nevertheless, in subgroup of patients with psychiatric disorders and advanced CRC stage, benzodiazepine could improve survival.

Brain-Derived Neurotrophic Factor (BDNF) Concentration Levels in Cerebrospinal Fluid and Plasma in Patients With Glioblastoma: A Prospective, Observational, Controlled Study.

Objective Glioblastomas (GBMs) are among the most frequent and most malignant of untreatable brain tumors. A GBM marker could accelerate diagnosis and facilitate therapeutic monitoring. This prospective, observational, controlled study compared brain-derived neurotrophic factor (BDNF) levels in cerebrospinal fluid (CSF) and plasma between patients with GBM and a control group. Materials and methods Patients in the observational group underwent elective GBM resection (n=24, 55.8%).Control patients (n=19, 44.2%) had elective brain surgery for an unrelated, non-neoplastic, non-traumatic pathology. We measured BDNF levels in tumors, CSF, and plasma with enzyme-linked immunosorbent assay (ELISA). Peripheral blood and CSF samples were collected before surgery, and tumors were sampled intraoperatively. We analyzed correlations between BDNF levels and patient sex, age, seizures, smoking, diabetes mellitus (DM), and the use of selected antiepileptic drug (AED) and antihypertensive drug groups. Results The mean CSF BDNF concentration was significantly lower in patients with GBM (6.5 pg/mL) than in controls (11.48 pg/mL) (p=0.002). Similarly, the mean plasma BDNF concentration was significantly lower in patients with GBM (288.59 pg/mL) than in controls (574.06 pg/mL) (p=0.0005). None of the examined factors influenced CSF, plasma, or tumor tissue BDNF concentrations (p>0.05). Conclusion Plasma and CSF BDNF levels were significantly lowerin adults with GBM than in controls. Thus, CSF and plasma BDNF levels may aid in GBM diagnoses. Further prospective studies are required.

Increased academic stress is associated with decreased plasma BDNF in Chilean college students

Introduction Academic stress (AS) is a prevalent challenge faced by university students, potentially affecting molecular indicators such as brain-derived neurotrophic factor (BDNF) and global DNA methylation (G-DNA-M). These indicators could illuminate the physiological ramifications of academic stress. Study Design and Methods This research followed a quantitative, non-experimental, longitudinal panel design spanning two academic semesters, observing phenomena in their natural context. Students from the Medical Technology program at Universidad de Concepción, Chile were involved, with assessments at the beginning and during heightened academic stress periods. Sample Of the total participants, 63.0% were females, with an average age of 21.14 years at baseline, and 36.92% were males, averaging 21.36 years. By the study’s conclusion, female participants averaged 21.95 years, and males 22.13 years. Results Significant differences were observed between initial and final assessments for the SISCO-II Inventory of Academic Stress and Beck Depression Inventory-II, notably in stressor scores, and physical, and psychological reactions. Gender differences emerged in the final physical and psychological reactions. No significant changes were detected between the two assessments in plasma BDNF or G-DNA-M values. A refined predictive model showcased that, on average, there was a 3.56% decrease in females’ plasma BDNF at the final assessment and a 17.14% decrease in males. In the sample, the G-DNA-M percentage at the final assessment increased by 15.06% from the baseline for females and 18.96% for males. Conclusions The study underscores the physiological impact of academic stress on university students, evidenced by changes in markers like BDNF and G-DNA-M. These findings offer an in-depth understanding of the intricate mechanisms regulating academic stress responses and highlight the need for interventions tailored to mitigate its physiological and psychological effects.

Effect of modernized collaborative care for depression on brain-derived neurotrophic factor (BDNF) and depressive symptom clusters: Data from the eIMPACT trial

Brain-derived neurotrophic factor (BDNF) levels are lower in people with depression and are normalized following pharmacological treatment. However, it is unknown if psychological treatments for depression improve BDNF and if change in BDNF is a mediator of intervention effects on depressive symptoms. Therefore, using data from the eIMPACT trial, we sought to determine the effect of modernized collaborative care for depression on 12-month changes in BDNF and cognitive/affective and somatic depressive symptom clusters and to examine whether BDNF changes mediate intervention effects on depressive symptoms. 216 primary care patients with depression from a safety net healthcare system were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. Plasma BDNF was measured with commercially available kits, and depressive symptom clusters were assessed by the Patient Health Questionnaire-9. The intervention did not influence BDNF but did improve both the cognitive/affective and somatic clusters over 12 months. Changes in BDNF did not mediate the intervention effect on either cluster. Our findings suggest that modernized collaborative care is an effective treatment for both the cognitive/affective and somatic symptoms of depression and that the mechanism of action is not improvements in BDNF. Trial registrationClinicalTrials.gov Identifier: NCT02458690