Serum Brain-derived Neurotrophic Factor Concentrations Research Articles

Treating Agitation in Patients with Dementia with a Therapy Dog in a Milieu Therapy Setting on a Geropsychiatric Ward

Background: Animal-assisted intervention has become a common therapeutic practice used for patients with dementia in home-dwelling and institutions. The most established procedure is a visiting service by specially trained dogs and their owners to improve social interactions and reduce symptoms of agitation. Objectives: The study aims to investigate the effects of a therapy dog on agitation of inpatients with dementia in a gerontopsychiatric ward. Materials and Methods: The severity of agitation was assessed by a rater blinded for the presence of the dog via the Overt Agitation Severity Scale (OASS). The scale was conducted on 1 day with the dog and his handler present (resident doctor on the ward) and on another day with only the handler present. Each patient was his/her own control. Heart rate variability (HRV) and serum level of brain-derived neurotrophic factor (BDNF) of the patients were measured on both days. 26 patients with the Mini-Mental Status Examination (MMSE) score <21 and the diagnosis of dementia were included in the study. Results: A significant reduction of agitation in the OASS could be shown when the dog was present (p = 0.006). The data neither demonstrated a difference in the HRV for the parameters mean heart rate (p = 0.65), root mean square of successive differences (p = 0.63), and high frequencies (p = 0.27) nor in serum BDNF concentrations (p = 0.42). Discussion: Therapy dogs can be implemented as a therapeutic tool in a gerontopsychiatric ward to reduce symptoms of agitation in patients with dementia. The study was registered in the German Clinical Trials Register (DRKS00024093).

Changes in serum brain derived neurotrophic factor following high intensity interval training among obese undergraduates

The study examined changes in Serum Brain Derived Neurotrophic Factor (BDNF) following High Intensity Interval Training (HIIT) programme among obese undergraduates. The pretest-posttest randomized experimental design was employed for the study. The population of the study comprised one hundred and twenty (120) obese undergraduates, out of which a total of twenty-four (24) obese undergraduates made up the sample for the study. Simple random sampling technique was employed to select the participants. The anthropometric profiles of the participants were descriptively analyzed using mean and standard deviation, while independent sample t-test was used to test the hypothesis. Statistical significance was accepted at p value of &lt;0.05. The results obtained indicated an increase in Serum BDNF (1.05 1.4 vs 1.42 2.2) among HIIT group, with no statistical significant difference. It was therefore concluded that the HIIT protocol-initiated alterations in the serum BDNF concentration of the obese undergraduates. HIIT may represent an effective intervention for elevating BDNF levels, as well as potentially promoting brain health. It was recommended that further research with prolonged exercise duration and larger sample size is required to elicit statistical significance, as well as to confirm the finding that increased serum BDNF levels are associated with HIIT intervention among obese undergraduate population.

Dietary Macronutrients Do Not Differently Influence Postprandial Serum and Plasma Brain-Derived Neurotrophic Factor Concentrations: A Randomized, Double-Blind, Controlled Cross-Over Trial.

Objectives: Brain-derived neurotrophic factor (BDNF) plays a role in cognition and metabolism. Specific nutrients can affect fasting BDNF concentrations, which are potentially mediated by insulin and/or glucose. Since macronutrients trigger each a different insulin and glucose response, we examined postprandial effects of meals rich in fat, carbohydrates, or protein on BDNF concentrations. BDNF was analyzed in serum and plasma, since concentration differences can be found between matrices.Methods: Healthy overweight/obese male participants (n = 18) participated in this randomized, double-blind, cross-over trial consisting of three test days with 1 week wash-out periods. Either a high-fat (En% fat, carbohydrates, protein: 52.3, 39.2, 8.0), high-carbohydrate (En% 9.6, 81.5, 8.6) or high-protein meal (En% 10.6, 51.5, 36.9) was consumed on each test day. BDNF concentrations were measured after 0, 60, and 240 min. Glucose and insulin concentrations were measured after 0, 15, 30, 45, 60, 90, 120, and 240 min.Results: BDNF concentrations were higher in serum compared with plasma (P < 0.001). Postprandial BDNF concentrations in serum decreased significantly after the high-fat (P = 0.013) and high-carbohydrate meals (P = 0.040), and showed a trend after the high-protein meal (P = 0.076). No differences were found between meals (P = 0.66). Postprandial BDNF concentrations measured in plasma did not significantly change after the different meals (P = 0.47). As total area under the curve (AUC) for glucose was significantly higher after the high-carbohydrate meal compared with the high-fat (P = 0.003) and high-protein meals (P < 0.001), and the total AUC for insulin was higher after the high-carbohydrate (P < 0.001) and high-protein meals (P < 0.001) compared with the high-fat meal, it seems that acute changes in glucose and insulin do not affect postprandial BDNF concentrations. However, after the high-protein meal, the higher total AUC for glucose correlated with lower serum BDNF concentrations, and a higher maximal increase in glucose correlated with a lower maximal increase in plasma BDNF concentrations. There were no correlations with insulin concentrations after either meal.Conclusion: Serum BDNF concentrations were higher than plasma concentrations. Since postprandial BDNF responses were not different between the meals, we conclude that there is no role for insulin or glucose in regulating postprandial BDNF concentrations.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03139890].

COVID-19 Outcome Relates With Circulating BDNF, According to Patient Adiposity and Age.

Background and Aims: We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease.Methods: This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines.Results: We demonstrate that BDNF levels predict intensive care (IC) need (p < 0.01). This association was found to be stronger in patients >60y (p = 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p < 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p = 0.023). In older patients, BDNF concentration was lower than that of younger patients (p = 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status.Conclusion: Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.

Serum and plasma brain-derived neurotrophic factor concentration are elevated by systemic but not local passive heating.

Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal adaptations. While previous studies suggest that whole-body heating can elevate circulating BDNF concentration, this is not known for local heating protocols. This study investigated the acute effects of whole-body versus local passive heating on serum and plasma BDNF concentration. Using a water-perfused suit, ten recreationally active males underwent three 90 min experimental protocols: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and a control condition (CON). Blood samples were collected before, immediately after and 1 h post-heating for the determination of serum and plasma BDNF concentration, platelet count as well as the BDNF release per platelet. Rectal temperature, cardiac output and femoral artery shear rate were assessed at regular intervals. Serum and plasma BDNF concentration were elevated after WBH (serum: 19.1±5.0 to 25.9±11.3 ng/ml, plasma: 2.74±0.9 to 4.58±2.0; p<0.044), but not LBH (serum: 19.1±4.7 to 22.3±4.8 ng/ml, plasma: 3.25±1.13 to 3.39±0.90 ng/ml; p>0.126), when compared with CON (serum: 18.6±6.4 to 16.8±3.4 ng/ml, plasma: 2.49±0.69 to 2.82±0.89 ng/ml); accompanied by an increase in platelet count (p<0.001). However, there was no change in BDNF content per platelet after either condition (p = 0.392). All physiological measures were elevated to a larger extent after WBH compared with LBH (p<0.001), while shear rate and rectal temperature were higher during LBH than CON (p<0.038). In conclusion, WBH but not LBH acutely elevates circulating BDNF concentration. While these findings further support the use of passive heating to elevate BDNF concentration, a larger increase in shear rate, sympathetic activity and/or rectal temperature than found after LBH appears needed to induce an acute BDNF response by passive heating.

The contribution of platelets to peripheral BDNF elevation in children with autism spectrum disorder

Brain-derived neurotrophic factor (BDNF), a key peptide in neurocognitive development, has been reported to be elevated in the serum of children with autism spectrum disorder (ASD). In a few studies, however, no differences or the converse have been documented. As a secondary analysis of a natural history study, we examined differences in ELISA serum BDNF between a group of children aged 1 to 9 years (69% white) with ASD (n = 94) and those with typical development (n = 52) or non-ASD developmental delay (n = 21), while accounting for the potential confounding effects of platelet quantity. Platelet counts were measured within 4 h of blood draw using an automated cell counter. Taqman single nucleotide polymorphism (SNP) assays were used to genotype 11 SNPs within the BDNF locus. Unadjusted mean BDNF concentration was higher in children with ASD than in children with typical development (standardized mean difference = 0.23; 95% CI 0.07, 0.38), but not children with non-ASD developmental delay. The magnitude of this difference was reduced after adjusting for platelet count (standardized mean difference = 0.18; 95% CI 0.02, 0.33). Although some BDNF SNPs were related to BDNF concentration, the distributions of these genotypes did not differ across diagnostic groups. This study replicates previous work suggesting that average serum BDNF concentration is higher in ASD compared to typical development, and extends that work by highlighting the potentially confounding role of platelet counts. The etiology of platelet count differences warrants further elucidation. Nonetheless, our results suggest that elevation in BDNF may be partially explained by higher platelet counts in children with ASD, an association that should be considered in future analysis and interpretation.Registration: NCT00298246

Vitamin C supplementation promotes mental vitality in healthy young adults: results from a cross-sectional analysis and a randomized, double-blind, placebo-controlled trial

PurposeWe aimed to investigate the link of vitamin C status with vitality and psychological functions in a cross-sectional study, and examine their causal relationship through a randomized controlled trial (RCT).MethodsWe first conducted a population-based cross-sectional investigation of healthy young adults (n = 214, 20–39 years), and analyzed the associations of serum vitamin C concentrations with vitality (fatigue and attention) and mood status (stress, depression, and positive and negative affect) using Pearson’s correlation and multiple linear regression analyses. Next, we performed a double-blind RCT in healthy subjects whose serum vitamin C concentrations were inadequate (< 50 μmol/L). Subjects were randomly allocated to receive 500 mg of vitamin C twice a day for 4 weeks (n = 24) or a placebo (n = 22). We assessed vitality, which included fatigue, attention, work engagement, and self-control resources, and measured mood status, including stress, depression, positive and negative affect, and anxiety. ELISA determined serum brain-derived neurotrophic factor (BDNF), and a Stroop color–word test evaluated attention capacity and processing speed.ResultsIn the cross-sectional data, the serum vitamin C concentration was positively associated with the level of attention (r = 0.16, p = 0.02; standardized β = 0.21, p = 0.003), while no significant associations with the levels of fatigue and mood variables being found. In the RCT, compared to the placebo, the vitamin C supplementation significantly increased attention (p = 0.03) and work absorption (p = 0.03) with distinct tendency of improvement on fatigue (p = 0.06) and comprehensive work engagement (p = 0.07). The vitamin C supplementation did not affect mood and serum concentrations of BDNF. However, in the Stroop color–word test, the subjects supplemented with vitamin C showed better performance than those in the placebo group (p = 0.04).ConclusionInadequate vitamin C status is related to a low level of mental vitality. Vitamin C supplementation effectively increased work motivation and attentional focus and contributed to better performance on cognitive tasks requiring sustained attention.Trial registration number and date of registrationCross-sectional study: KCT0005074 (cris.nih.go.kr)/1 June, 2020 (retrospectively registered). Intervention study: KCT0004276 (cris.nih.go.kr)/4 September, 2019.

Clinical and laboratory markers of early diagnosis of diabetic polyneuropathy

Objective. To study the content of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor of type B kinase (TrkB) in patients at an early stage of diabetic polyneuropathy. Late diagnosis of diabetic polyneuropathy (DPN) is largely due to the presence of a subclinical stage, at which damage to the nervous system develops in the absence of complaints from the patient.&#x0D; Materials and methods. 64 patients with type 2 diabetes mellitus and 11 persons of the control group were examined with an assessment of the pain status and the degree of peripheral neuropathy using PainDetect, TSS, NSS, NDS scales. Disturbance of nerve conduction along the nerves of the lower extremities was studied using electroneuromyography (ENMG). The study of the quantitative content of BDNF and TrkB in the serum was carried out with enzyme immunoassay.&#x0D; Results. The increased serum concentrations of BDNF (p = 0.001) and TrkB (p = 0.007) were found with the development of clinically evident DPN as compared to patients without DPN. In patients with diabetes mellitus with subclinical DPN, there was established a statistically significant increase in serum BDNF expression (2.97 [2.44; 3.37] ng/ml in comparison with the values both in the control group (p = 0.022) and in diabetic patients without DPN (p = 0.017). The mean TrkB level in this group was 4.29 [3.48; 5.62] ng/ml, that is also higher than the corresponding values for patients without DPN (p = 0.032) and the control group (p = 0.025). The serum BDNF level correlates with the duration of diabetes mellitus (R = 0.524; p = 0.02), the intensity of neuropathic pain (R = 0.402; p = 0.001), the degree of axonal damage according to ENMG data (R = -0.242; p = 0.03). Correlations between the serum TrkB content and the severity of diabetes mellitus course (R = 0.482; p = 0.01), pain intensity (R = 0.383; p = 0.001), and impaired nerve conduction (R = 0.359; p = 0.003) were found.&#x0D; Conclusions. The elevated expression and increased serum concentrations of BDNF and TrkB occur at the initial stage of the damage of peripheral nerve fibers and correlate with the degree of compensation for carbohydrate metabolism, the duration of diabetes and the severity of neural conduction disorders. The data obtained allow us to consider the increased serum levels of BDNF and TrkB as the markers of subclinical stage of diabetic polyneuropathy.

Extra-Virgin Olive Oil Improves Depression Symptoms Without Affecting Salivary Cortisol and Brain-Derived Neurotrophic Factor in Patients With Major Depression: A Double-Blind Randomized Controlled Trial

BackgroundMany patients with depression are reluctant to take psychiatric medications. Hence, complementary therapies such as nutritional considerations could be advantageous. The antidepressant potential of olive oil has been proved in observational studies. ObjectiveThe effect of extra-virgin olive oil (EVOO) on depression symptoms and cortisol and brain-derived neurotrophic factor (BDNF) levels in patients with depression was examined. Design and participantsThis was a double-blind randomized controlled trial conducted on 73 patients suffering from major depressive disorder in Shiraz, Iran, in 2016. InterventionThe patients were randomly assigned to intervention (EVOO) and control (sunflower oil) groups and consumed 25 mL/d of the corresponding oil for 52 days. Main outcome measuresDepression symptoms were assessed by Beck Depression Inventory-II (BDI-II) and 7-item Hamilton Depression Rating Scale (HAMD-7). Salivary cortisol levels were determined immediately after awakening and 30 minutes later. Cortisol awakening response and the area under the curve with respect to ground and increase were computed. Serum BDNF concentrations were also measured. Statistical analyses performedStatistical analysis was conducted based on intention-to-treat and per-protocol approaches. Within-group changes were examined with repeated measures (for BDI-II and HAMD-7) and with paired t test (for other variables). Between-group comparisons were performed with analysis of covariance after adjustment for confounding factors. ResultsIn intention-to-treat analysis, HAMD-7 score was the only variable with significant changes within and between groups, the latter as a greater decline in EVOO group (P = .001). BDI-II score did not show significant change in either group but the between-group comparison revealed a significant difference (P = .021). EVOO showed antidepressant effect in severely depressed patients (P = .017 for BDI-II and 0.008 for HAMD-7) but not in mild/moderate depression category. Serum BDNF concentrations, salivary cortisol levels at immediately after awakening (T0) and 30 minutes later, cortisol awakening response, the area under the curve with respect to ground and increase did not change within or between groups. Results of per-protocol analysis were not different. ConclusionsThe results of this study suggested beneficial effects of EVOO on depression symptoms in patients with severe depression but not in those with mild to moderate depression. The effects were significant from both statistical and clinical points of view.

Decreased Serum Brain-Derived Neurotrophic Factor Concentrations 72 Hours Following Marathon Running.

Background: Physical exercise has been linked to beneficial effects on brain plasticity. One potential key mechanism for this relationship is an exercise-induced increase of brain-derived neurotrophic factor (BDNF). However, the kinetics of BDNF in athletes during training phase, extreme exercise competition, and recovery period have not been investigated so far.Methods: We assessed serum BDNF concentrations in 51 marathon runners (23% female, mean age 43 years) in a longitudinal study design over a period of 6 months. Assessments were conducted during the training period before the marathon and after the marathon race during short-term (24 to 72 h) and long-term (3 months) follow-ups. Potential confounders (fitness level, sex, and platelet count) were included in subsequent linear-model analyses.Results: Linear mixed-model analyses revealed a main effect of time for BDNF concentrations over the study period (F(4,89.389) = 4.296, p = 0.003). Values decreased significantly with the lowest values at 72 h after the marathon compared to baseline (p = 0.025), a finding that was more pronounced in the larger male cohort.Conclusion: Prolonged exercise induces a significant decrease in serum BDNF concentration 72 h post-exercise. We assume that this observation is mainly driven by regenerative mechanisms and a higher muscular utilization.

Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Theory of Mind and Executive Function in Major Depressive Disorder and Its Correlation with Brain-Derived Neurotrophic Factor (BDNF): A Randomized, Double-Blind, Sham-Controlled Trial.

Background: Studies have implicated hypofrontality in the pathogenesis of impaired theory of mind (ToM) and executive function (EF) in major depressive disorder (MDD). These symptoms are usually resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS) has been shown to reverse hypofrontality. Moreover, BDNF is an effective biomarker of antidepressant effects, but there have been very few studies on the correlation between BDNF and rTMS. We aimed to evaluate the efficacy of 20 sessions of a 10 Hz unilateral rTMS intervention over the left dorsolateral prefrontal cortex (DLPFC) in improving ToM and EF in patients with MDD and its correlation with BDNF. Methods: A total of 120 MDD patients were enrolled in this randomized, sham-controlled, double-blind trial. Each participant received 20 sessions of rTMS at 10 Hz frequency through the active or the sham coil over 4 weeks. ToM was assessed with the facial emotion identification test (FEIT) and hinting task (HT). EF was assessed with the Wisconsin card sorting test (WCST). BDNF assessments were carried out at baseline and 2-, 4-, 12-, and 24-week follow-ups. Results: The improvement in the ToM (FEIT, HT) in the active rTMS group was significantly different from that in the sham rTMS group (F = 18.09, p < 0.001; F = 5.02, p = 0.026). There were significant differences in the WCST (categories completed, response errors, response perseverative errors, non-response perseverative errors) after logarithmic transformation at different time points in the active rTMS group (F = 14.71, p < 0.001; F = 5.99, p = 0.046; F = 8.90, p = 0.031; F = 2.31, p = 0.048). However, there was no significant difference in log transformed BDNF concentration between the two groups (t = 0.07 to t = 1.29, p > 0.05). BDNF was negatively correlated with WCST categories completed at the 24th week (r = −0.258, p = 0.046). Conclusions: The results show that rTMS may improve the ToM and EF of patients with MDD and there was no significant correlation with serum BDNF concentration. RTMS can not only be used for treatment of patients with MDD but also has a positive effect on ToM and EF.

MO445BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION PROTEINS

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive systemic disease that affect the microvascular permeability of the blood-brain barrier (BBB) and intestinal barrier leading to increased morbidity, mortality and central nervous system symptoms. In this study we examined the relationship of blood brain and intestinal barrier dysfunction in relation to uraemic environment and increased risk of developing neurologic complications and mortality. In addition, potential proteins conferring the junctional communications were assessed. Method The study included serum samples from 216 prevalent haemodialysis (HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was evaluated by measuring serum concentrations for brain-specific biomarkers S100B, NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate of gut generated uraemic toxins was analysed by mass spectrophotometry. Subcutaneous fat tissues with identified microvessels from 10 kidney transplant recipients and 11 donors were examined for expression of tight junction proteins claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by immunohistochemical staining. Results HD and PD groups showed elevated cholesterol, triglyceride, creatinine, hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration were also higher in both HD (6.4 ng/μL, IQR 4.0-11.2) and PD (3.8 ng/μL, IQR 2.2-6.3) vs controls (0.4 ng/μL, IQR 0.3-0.6). No significant sex differences in biomarker concentration were found, except for TMAO in healthy controls. Immunohistochemistry studies of endothelial tight junction proteins in microvessels, within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and 8%, respectively), and ongoing studies are indicating a trend for altered expression of tight junction proteins after ex vivo stimulation with TMAO. Conclusion We report that CKD5 patients showed disruption of BBB and intestinal barrier resulting in altered circulating serum levels of brain-specific biomarkers, secondary to a disruption in the tight junction protein markers in microvasculature of adipose tissue. These findings imply that it is important to continuously monitor cognitive function(s) in CKD. Further studies are needed to assess direct effect of TMAO on tight junction proteins which confer vascular permeability.

The effects of wheat germ consumption on mental health and brain-derived neurotrophic factor in subjects with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial

ABSTRACT Objectives: Herbals, as bioactive foods, have been one of the most popular alternatives and complementary treatments in preventing and controlling type 2 diabetes mellitus (T2DM). The aim of the present trial was to examine the effects of wheat germ consumption on mental health and brain-derived neurotrophic factor (BDNF) among patients with T2DM. Methods: Eighty participants with T2DM were randomly allocated to receive 20 g wheat germ (n = 40) or placebo (n = 40) in a randomized double-blind clinical trial for 12 weeks. Depression, anxiety, stress scale-21 (DASS-21) questionnaire was used to assess the mental health of study participants. Serum BDNF was assessed at the baseline and end of intervention. Anthropometric indices were measured at the baseline, 6 and 12 weeks during the intervention. Results: A total of 75 subjects completed the trial. Compared with the placebo, wheat germ consumption led to a significant reduction in depression (P = .03) and stress (P = .04) scores. Moreover, a significant increase in serum BDNF concentrations was observed in the wheat germ group (P = .004), while there was no significant difference between the groups. Wheat germ intake had no significant effects on anthropometric indices and anxiety scores between the groups. Conclusion: Our findings showed that wheat germ consumption for 12 weeks could significantly reduce the stress and depression scores but had no significant effects on anxiety scale and anthropometric outcomes in patients with T2DM.

The effects of interval training on peripheral brain derived neurotrophic factor (BDNF) in young adults: a systematic review and meta-analysis

The aim of the current meta-analysis was to determine the effects of acute and chronic interval training (IT) on serum and plasma BDNF concentrations in healthy young adults. A literature search was performed using six databases until February 2020. The TESTEX scale was used to assess the quality of studies. Effect sizes (ES) were computed and two-tailed α values < 0.05 and non-overlapping 95% confidence intervals (95% CI) were considered statistically significant. Heterogeneity, inconsistency (I2), and small-study effects using the Luis Furuya–Kanamori (LFK) index were examined. Fifteen studies (n = 277 participants, age = 24 ± 3 years) were included. The overall effects of IT on circulating BDNF concentrations were moderate and significant (ES = 0.62, 95% CI 0.00, 1.24, heterogeneous (p < 0.001), highly inconsistent (I2 = 90%), and with major asymmetry (LFK index = 2.76). The acute effect of IT on peripheral BDNF levels was large and significant (ES = 1.10, 95% CI 0.07, 2.14), heterogeneous (p < 0.001), highly inconsistent (I2 = 92%), and with major asymmetry (LFK index = 3.34). The chronic effect of IT on circulating BDNF was large and significant (ES = 0.93, 95% CI 0.40, 1.46), heterogeneous (p < 0.001), with moderate inconsistency (I2 = 70%), and minor asymmetry (LFK index = 1.21). Acute and chronic IT elicited a moderate increase in serum and plasma BDNF concentrations in a healthy young population.

Serum Levels of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Elite Athletes: Potential Markers of the Use of Transcranial Direct Current Stimulation in Sport.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation that may enhance mental and physical performance in sports, representing a potential new form of doping (“brain doping” or “electromagnetic doping”). This study aims to identify diagnostic biomarkers for detecting the possible abuse of tDCS in sport. Brain-Derived Neurotrophic Factor (BDNF) and other neurotrophins (NT, such as beta nerve growth factor, NGF) were pre-selected as potential candidates since their serum values have been observed to change following tDCS. Neurotrophins were measured using ELISA assays in 92 serum samples collected from elite athletes, classified by sex (males = 74; females = 18), age (range 17–25 n = 27, 26–35 n = 36, and over 35 n = 14; age not known n = 15), type of sports practiced (endurance n = 74; power n = 18), and type of sample collection (“in competition” n = 24; “out of competition” n = 68). Single nucleotide polymorphisms (rs6265, rs11030099, and rs11030100) were genotyped on 88 samples to determine their influence on the analytes' basal levels. Athletes older than 35 presented higher BDNF values than younger individuals (p < 0.05). Samples collected “in competition” showed higher BDNF concentrations than those collected “out of competition” (p < 0.05). The studied polymorphisms appeared to affect only on proBDNF, not altering BDNF serum concentrations. NT-3 and NT-4 were poorly detectable in serum. Our results suggest that BDNF can be considered as a first biomarker to detect the abuse of tDCS in sport doping. Further studies are necessary to assess whether proBDNF and beta NGF can also be considered suitable biomarkers to detect the recourse to electromagnetic brain stimulation in sports, especially in the case their serum levels can be monitored longitudinally. To the best of our knowledge, this is the first study aimed to pre-select serum biomarkers to identify the use of tDCS, and represents the first step toward the development of an indirect strategy, preferably based on the longitudinal monitoring of individual data, for the future detection of “brain doping” in sports.

Is Serum BDNF Altered in Acute, Short- and Long-Term Recovered Restrictive Type Anorexia Nervosa?

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all.

Effects of Positive Human Contact during Gestation on the Behaviour, Physiology and Reproductive Performance of Sows.

Simple SummaryStress can compromise animal welfare and impact the productivity of farm animals. In intensive production systems where close interactions between stockpeople and animals occur regularly, human contact of a positive nature may facilitate stress resilience. This experiment studied the effects of human interaction on stress in pigs, by providing sows in their home pens with either regular positive handling by stockpeople or routine human contact. Stress resilience was studied by assessing the behaviour, physiology and productivity of pigs in these two treatments. Positive human contact was effective at reducing the fear responses of sows towards stockpeople conducting routine husbandry practices in the home pens. However, the positive handling treatment did not affect the behaviour of pigs towards other stressors imposed outside of the home pen, acute or basal physiological measures of stress or reproductive performance. Sows receiving positive handling showed reduced physical interaction with the stockpeople delivering the treatment over time, which may indicate habituation to the novel or possible rewarding elements of the human contact treatment. This work confirms that regular positive interaction with stockpeople does reduce the fear of sows to stockpeople, but does not always confer stress resilence.Previous positive interactions with humans may ameliorate the stress response of farm animals to aversive routine practices such as painful or stressful procedures, particularly those associated with stockpeople. We studied the effects of positive handling by providing younger (parity 1–2) and older (parity 3–8) sows housed in pens of fifteen (n = 24 pens in total) with either positive human contact (+HC) or routine human contact (control) during gestation. The +HC treatment involved a familiar stockperson patting and scratching sows and was imposed at a pen-level for 2 min daily. Measurements studied included behavioural, physiological and productivity variables. The +HC sows showed reduced avoidance of the stockperson conducting pregnancy testing and vaccination in the home pens, however the behavioural and cortisol responses of sows in a standard unfamiliar human approach test did not differ. There were no effects of +HC on aggression between sows, serum cortisol or serum brain-derived neurotrophic factor concentrations during gestation, or on the behavioural and cortisol response to being moved to farrowing crates. There were also no effects of +HC on the maternal responsiveness of sows, farrowing rate or the number of piglets born alive, stillborn or weaned. Sows in the +HC pens reduced their physical interaction with the stockpeople imposing the treatment after 2 weeks, which suggests the sows may have habituated to the novel or possible rewarding elements of the handling treatment. This experiment shows that regular positive interaction with stockpeople does reduce sows’ fear of stockpeople, but does not always confer stress resilence.

The effects of endurance exercise combined with high-temperature head-out water immersion on serum concentration of brain-derived neurotrophic factor in healthy young men

Objectives To evaluate acute changes in serum brain-derived neurotrophic factor (BDNF) concentration following combined endurance exercise and heat stress through head-out water immersion (HOI). Setting Observational study with crossover design. Methods Ten healthy young male participants performed HOI at 40 °C (40 °C HOI) or continuous cycling at 60% of maximal oxygen uptake while immersed in 40 °C (40 °C HOI-ex) or 23 °C water (23 °C HOI-ex) for 15 min. Serum BDNF, cortisol and lactate concentrations, and core temperature (Tcore) were measured pre, immediately post, and 15 and 30 min post-immersion. Results BDNF concentration increased immediately and 15 min after 40 °C HOI-ex, but not after 40 °C or 23 °C HOI-ex. No changes in Tcore concentration were observed during 23 °C HOI-ex (Pre; 37.3 °C ± 0.3 °C, Post; 37.8 °C ± 0.2 °C, Post 15; 37.4 °C ± 0.3 °C, Post 30; 37.2 °C ± 0.2 °C). Tcore increased significantly post, post 15, and post 30 min of 40 °C HOI (Pre; 37.1 °C ± 0.4 °C, Post; 38.8 °C ± 0.5 °C, Post 15; 37.9 °C ± 0.4 °C, Post 30; 37.9 °C ± 0.2 °C) and 40 °C HOI-ex (Pre; 37.2 °C ± 0.2 °C, Post; 40.2 °C ± 0.7 °C, Post 15; 38.9 °C ± 0.5 °C, Post 30; 38.3 °C ± 0.5 °C). Tcore was higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex immediately post and post 15 min. Plasma lactate and cortisol were significantly higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex after immersion (p = 0.001). Conclusion While 15 min HOI alone or thermoneutral exercise do not increase BDNF concentration, both combined may form a time-efficient strategy to acutely elevate BDNF.

Brain-derived neurotrophic factor as a potential diagnostic marker in minimal hepatic encephalopathy.

IntroductionMinimal hepatic encephalopathy (MHE) is a common complication of liver cirrhosis not only leading to a decrease in the quality of life, but also predicting development of overt encephalopathy. The diagnosis of MHE usually relies on a combination of neuropsychological tests, while robust serum biomarkers are lacking. We aimed to assess serum concentrations of brain-derived neurotrophic factor (BDNF) in MHE patients.Material and methodsSerum BDNF was assessed in 78 patients with liver cirrhosis (53 male, median age 55 years) and 40 healthy individuals. 43 subjects underwent extensive evaluation for MHE by psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT) or critical flicker frequency (CFF).ResultsSerum BDNF was twofold lower in liver cirrhosis compared to healthy subjects [13.6 (7.8-22.6) vs. 33.0 (24.1-40.7) ng/ml, p < 0.001] and its decrease reflected a degree of liver insufficiency assessed by model for end-stage liver disease (MELD). BDNF showed a negative correlation with bilirubin (R = –0.35, p = 0.005) and international normalized ratio (INR) (R = –0.37, p = 0.003), and positive with platelets (PLT) (R = 0.36, p = 0.004), while no associations with age, sex, body mass index (BMI), waist-hip ratio (WHR), creatinine and ammonia were noted. Importantly, subjects with a diagnosis of MHE by at least two modalities showed the lowest levels of BDNF [10.9 (2.5-14.4) vs. 19.9 (9.3-29.4) ng/ml, p < 0.01]. Patients with self-reported sleep disturbances had significantly lower serum BDNF [13.0 (2.5-23.4) vs. 20.0 (8.4-31.3) ng/ml, p = 0.04].ConclusionsThe lowest serum BDNF concentration was noted in patients with MHE and sleep disturbances, which suggests a role in pathophysiology of hepatic encephalopathy but also as a potential biomarker.

The Association Between Adolescent Residential Mobility and Adult Social Anxiety, BDNF and Amygdala-Orbitofrontal Functional Connectivity in Young Adults With Higher Education.

Background: Large-scale epidemiological studies demonstrate that house moves during adolescence lead to an increase in anxiety and stress-sensitivity that persists into adulthood. As such, it might be expected that moves during adolescence have strong negative and long-lasting effects on the brain. We hypothesized that moves during adolescence impair fear circuit maturation, as measured by the connectivity between amygdala and orbitofrontal cortex, and expression of brain-derived neurotrophic factor (BDNF).Methods: We examined young adults with middle and high economic status recruited from the community using clinical interviews, self-report questionnaires, functional magnetic resonance imaging during an emotional faces task and during a 10 min rest phase, and serum BDNF serum concentration.Results: Out of 234 young adults, 164 did not move between ages 10 and 16 (i.e., moves with change of school), 50 moved once, and 20 moved twice or more than twice. We found relationships between adolescent moving frequency and social avoidance (pcorr = 0.012), right amygdala-orbitofrontal cortex connectivity (pcorr = 0.016) and low serum BDNF concentrations in young adulthood (pcorr = 0.012). Perceived social status of the mother partly mitigated the effects of moving on social avoidance and BDNF in adulthood.Conclusions: This study confirms previous reports on the negative and persistent effects of residential mobility during adolescence on mental health. It suggests that these effects are mediated by impairments in fear circuit maturation. Finally, it encourages research into protecting factors of moving during adolescents such as the perceived social status of the mother.