Blood Brain-derived Neurotrophic Factor Research Articles

Does brain-derived neurotrophic factor play a role in the association between maternal prenatal mental health and neurodevelopment in 2-year-old children?

ObjectiveTo evaluate the role of brain-derived neurotrophic factor (BDNF)—a crucial modulator of neural development and plasticity—in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. MethodsWe included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. ResultsThe average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (β = −0.32; 95 % CI: −0.55, −0.09), depression (β = −0.30; 95 % CI: −0.52, −0.08), and perceived stress (β = −0.41; 95 % CI: −0.71, −0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. LimitationsMaternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. ConclusionsPrenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment.

How does maternal anemia affect the levels of umbilical cord brain-derived neurotrophic factor?

ObjectiveIn this study, we aimed to evaluate the effect of maternal iron deficiency anemia on the umbilical cord level of brain-derived neurotrophic factor (BDNF), which plays a very important role in the central nervous system. MethodsOur research was planned as a quantitative, prospective, and analytical type of study. A total of 90 volunteers, term, singleton pregnant hospitalized in the Health Sciences University Ümraniye Training and Research Hospital Gynecology and Obstetrics Clinic between September 2021 and August 2022 were included in this study. While 45 of these pregnants were pregnant women with iron deficiency anemia (hemoglobin ≤ 110 g/L and serum ferritin level ≤ 12 μg/L), 45 cases were in the control group without iron deficiency anemia (hemoglobin > 110 g/L, serum ferritin > 12 μg/L). When pregnant were admitted to the hospital, blood samples were taken to analyze hemoglobin, mean cell volume (MCV), iron, unsaturated iron binding capacity, total iron binding capacity, serum ferritin, transferrin, and CRP levels. Also, we noted the maternal age, gravida, parity, birth weight, head circumference, type of birth, 1. minute Apgar score, and 5. minute Apgar score. During the delivery; after the umbilical cord had been clamped and cut, we took 5 cc of umbilical cord blood. Then, we put it in the serum-separating laboratory tubes. After we centrifuged these blood samples, we put the serum parts in the Eppendorf tubes to be stored at −80 degrees Celsius. At the end of the study, we calculated the level of BDNF using special human brain-derived neurotrophic factor ELISA kits. The umbilical cord BDNF levels of the maternal iron deficiency anemia group and the control group were compared statistically. ResultsWhen we evaluated the fetal umbilical cord BDNF values of 90 participants, the median value BDNF in the babies of 45 anemic mothers was 3.16 (IQR 0.73), and the median BDNF value of the babies of 45 healthy mothers was 5.37 (IQR 1.02). We found a statistical difference between BDNF and hemoglobin, hematocrit, MCV, and iron values between these two groups. ConclusionIn conclusion, the BDNF value of the babies of healthy individuals is higher than that of anemic individuals. Our study showed that the amount of BDNF in the umbilical cord blood was significantly affected by maternal iron deficiency anemia.

Stress during pregnancy and fetal serum BDNF in cord blood at birth

IntroductionAdverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans. MethodsPregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed. ResultsAfter a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (β=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (β=-0.562, 95% CI [-914.511, −60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex. ConclusionMaternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.

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).

Rehabilitation Exercises Supported by Monitor-Augmented Reality for Patients with High-Grade Glioma Undergoing Radiotherapy: Results of a Randomized Clinical Trial.

Exercise has been shown to improve quality of life (QoL) and even treatment outcomes in cancer patients. However, the evidence to support the benefits of exercise in patients with high-grade glioma (HGG) is limited. Therefore, we performed a randomized clinical trial (RCT) to examine the effect of augmented-reality-based rehabilitation exercises on physical and functional fitness, cognitive function, fatigue, mood, QoL, selected blood parameters, brain derived neurotrophic factor (BDNF), and S100 protein in patients with HGG. Adult patients with HGG scheduled to undergo radiotherapy after tumor resection were randomized to participate in an exercise program (experimental group, n = 25) or to receive usual care (controls, n = 22). Physical and mental fitness was measured at baseline, after the completion of radiotherapy, and at 3 months. The following tests were administered: Handgrip Strength Test; 6-Minute Walk Test; Time Up and Go test; Functional Independent Measure scale; Addenbrooke's Cognitive Examination III (ACE III); Hospital Anxiety and Depression Scale; Functional Cancer Therapy Assessment-Brain; and Functional Assessment of Chronic Illness Therapy-Fatigue. We also measured blood parameters, BDNF, and S100 protein levels. No significant changes were observed in the exercise group. However, the controls experienced a significant decrease in HGS and in the ACE III attention domain. No significant changes were observed in QoL, fatigue, BDNF, or S100 levels in either group. Augmented-reality-based exercise during radiation therapy may prevent loss of muscle strength and attention in patients with HGG.

Effect of alcohol on Brain-Derived Neurotrophic Factor (BDNF) blood levels: a systematic review and meta-analysis

Brain-Derived Neurotrophic Factor (BDNF) is a vital protein involved in neuronal development, survival, and plasticity. Alcohol consumption has been implicated in various neurocognitive deficits and neurodegenerative disorders. However, the impact of alcohol on BDNF blood levels remains unclear. This systematic review and meta-analysis aimed to investigate the effect of alcohol consumption on BDNF blood levels. A comprehensive search of electronic databases was conducted to identify relevant studies. Eligible studies were selected based on predefined inclusion criteria. Data extraction was performed, and methodological quality was assessed using appropriate tools. A meta-analysis was conducted to estimate the overall effect size of alcohol consumption on BDNF levels. A total of 25 studies met the inclusion criteria and were included in the final analysis. Alcohol use and BDNF blood levels were significantly correlated, according to the meta-analysis (p = 0.008). Overall, it was discovered that drinking alcohol significantly decreased BDNF levels (SMD: − 0.39; 95% CI: − 0.68 to − 0.10; I2: 93%). There was a non-significant trend suggesting that alcohol withdrawal might increase BDNF levels, with an SMD of 0.26 (95% CI: − 0.09 to 0.62; I2: 86%; p = 0.14). Subgroup analysis based on the source of BDNF demonstrated significant differences between the subgroups (p = 0.0008). No significant publication bias was observed. This study showed that alcohol consumption is associated with a significant decrease in BDNF blood levels. The findings suggest a negative impact of alcohol on BDNF levels regardless of alcohol dosage. Further studies are needed to strengthen the evidence and elucidate the underlying mechanisms.

Clinical Importance of Serum BDNF (Brain-Derived Neurotrophic Factor) Level for the Management of Pregnancies Complicated With Meconium-Stained Amniotic Fluid.

Objective The aim of this study was to investigate the association between poor neonatal outcomes and BDNF (brain-derived neurotrophic factor) levels. We aimed to predict the need for an emergency cesarean and prevent unnecessary interventions in cases complicated with meconium-stained amniotic fluid (MSAF). Methods This study was designed as a case-control study including three groups. Group A included pregnant women who underwent cesarean due to fetal distress. Group B included the women who delivered vaginally. Groups A and B had cases with the presence of meconium in the amniotic fluid. Group C as a control group had clear amniotic fluid. Demographic features, fetal outcomes, and maternal serum and fetal cord blood BDNF levels (Human BDNF ELISA Kit; Synonyms: ANON2, BULN2; Catalog no: E-EL-H0010 96T) were evaluated. Results No significant difference was found between patients with meconium and without meconium in terms of BDNF levels. However, the BDNF level was found to be significantly lowerif fetal distress had occurred with MSAF. Conclusions In conclusion, the study demonstrated that the level of maternal and fetal cord blood BDNF are both significantly lower when fetal distress occurs with the presence of MSAF.

Female Pattern Hair Loss and Negative Psychological Impact: Possible Role of Brain-derived Neurotrophic Factor (BDNF).

Female Pattern Hair Loss (FPHL) is considered the most common type of hair loss in females. Women with FPHL may suffer from psychological distress and defective social functioning. Patients with psychiatric and neurodegenerative disorders almost have a deficient brain and blood brain-derived neurotrophic factor levels (BDNF). This serum BDNF level may act as a diagnostic marker for negative psychological impact in FPHL patients. Evaluate the levels of serum BDNF in patients with FPHL and correlate its level to the severity of alopecia and the degree of psychological impact. Forty-six female patients with FPHL and 41 healthy age-matched female volunteers as a control were included in the study. Patients filled out a Dermatology Life Quality Index questionnaire. Both patients and controls filled Beck Depression Inventory, Beck Anxiety Inventory, and Perceived Stress Scale (PSS) questionnaires. Serum levels of BDNF were measured for all the participants using the ELISA technique. Patients with FPHL had significantly lower levels of BDNF and significantly higher Beck depression inventory score and PSS questionnaire scores. There is a significant negative correlation between serum levels of BDNF and Beck Depression Inventory, Beck Anxiety Inventory, and PSS questionnaire scores. Patients with FPHL are at a high risk to develop chronic stress and depression. The serum level of BDNF is a good predictor for the assessment of chronic stress and depression in FPHL patients.

High blood levels of brain-derived neurotrophic factor (BDNF) mRNA in early psychosis are associated with inflammatory markers

The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism (SNP) rs6265C > T, Val66Met, affects BDNF secretion and has been related to inflammatory processes. Both the rs6265 and BDNF protein levels have been widely investigated in neuropsychiatric disorders with conflicting results. In the present study we examined BDNF mRNA expression in blood considering the SNP rs6265 and its relationship with inflammatory markers in the early stages of psychosis. The rs6265 genotype and blood BDNF mRNA levels were measured in 34 at-risk mental states (ARMS) individuals, 37 patients with first-episode psychosis (FEP) and 42 healthy controls (HCs) by quantitative PCR and reverse transcription (RT)-qPCR using validated TaqMan assays. We also obtained measures of interleukin-6 (IL6) mRNA levels, fibrinogen, neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein. We identified that BDNF mRNA levels were associated with the rs6265 genotype in an allele-dose-dependent manner, with low expression levels associated with the T allele (Met substitution). Thus, we controlled for the rs6265 genotype in all analyses. Blood BDNF mRNA levels differed between diagnostic groups: patients with FEP exhibited higher blood BDNF mRNA levels than ARMS individuals, and the lowest levels were observed in HC. In addition, we observed significant correlations between BDNF mRNA levels and inflammatory markers (IL6 mRNA levels and NLR), controlled by the rs6265 genotype, in ARMS and FEP groups. This exploratory study suggests that the rs6265 genotype is associated with differential blood mRNA expression of BDNF that increases with illness progression and correlated with inflammation in the early stages of psychosis.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), somatic and fatigue symptoms in cardiovascular diseases comorbid major depressive disorder (MDD): A randomized controlled trial

IntroductionCardiovascular diseases (CVDs) and major depressive disorder (MDD) are the two most disabling diseases. Patients with CVDs comorbid depression had somatic and fatigue symptoms and were associated with chronic inflammation and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficits. However, there have been limited studies on the effects of n-3 PUFAs on somatic and fatigue symptoms in patients with CVDs comorbid MDD. MethodForty patients with CVDs comorbid MDD (58% males, mean age of 60 ± 9 years) were enrolled and randomised to receive either n-3 PUFAs (2 g of eicosapentaenoic acid [EPA] and 1 g of docosahexaenoic acid[DHA] per day) or placebo in a 12-week double-blind clinical trial. We assessed the somatic symptoms with Neurotoxicity Rating Scale (NRS) and fatigue symptoms with Fatigue Scale at baseline, weeks 1, 2, 4, 8 and 12, as well as blood levels of Brain-Derived Neurotrophic Factor (BDNF), inflammatory biomarkers and PUFAs, at the baseline and week 12. ResultsThe n-3 PUFAs group had a greater reduction in Fatigue scores than the placebo group at Week 4 (p =.042), while there were no differences in the changes of NRS scores. N-3 PUFAs group also had a greater increase in EPA (p =.001) and a greater decrease in total n-6 PUFAs (p =.030). Moreover, in the subgroup analyses in the younger age group (age < 55), the n-3 PUFAs group had a greater reduction on NRS total scores at Week 12 (p =.012) and NRS Somatic scores at Week 2 (p =.010), Week 8 (p =.027), Week 12 (p =.012) than the placebo group. In addition, the pre- and post-treatment changes of EPA and total n-3 PUFAs levels were negatively associated with the changes of NRS scores at Weeks 2, 4, and 8 (all p <.05), and the changes of BDNF levels were negatively associated with NRS scores at Weeks 8 and 12 (both p <.05) in the younger age group. In the older age group (age ≥ 55), there were a lesser reduction on NRS scores at Weeks 1, 2 and 4 (all p <.05), but a greater reduction on Fatigue score at Week 4 (p =.026), compared to the placebo group. There was no significant correlation between the changes of blood BDNF, inflammation, PUFAs and NRS and Fatigue scores in general and in the older age group. ConclusionOverall, n-3 PUFAs improved the fatigue symptoms in patients with CVDs comorbid MDD and the general somatic symptoms in specific subpopulation of younger age patients, and perhaps via the interplay between BDNF and EPA. Our findings provide promising rationales for future studies to investigate the treatment effects of omega-3 fatty acids on fatigue and somatic symptoms of chronic mental and medical diseases.

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Can exercise prevent the age‐related decline in adaptive homeostasis? Evidence across organisms and tissues

Maternal exposure to fine particulate matter and brain-derived neurotrophic factor (BDNF) in the fetus: A prospective cohort study

Maternal exposure to ambient fine particulate matter (PM2.5) during pregnancy has been associated with impaired neurobehavioral development in children. However, the specific mechanism remains unclear. Brain derived neurotrophic factor (BDNF) is an important growth factor in the nervous system. We evaluated the associations of maternal PM2.5 exposures with fetal BDNF in the umbilical cord blood in a prospective cohort study. A total of 711 eligible mother-infant pairs from the Shanghai Birth Cohort were included in the current study. Daily maternal exposures to ambient PM2.5 were assessed with a gap-filling approach at 1 * 1 km2 resolution based on self-reported home addresses. The concentrations of BDNF in the cord blood were measured by ELISA. A linear regression model was applied to evaluate the association of maternal ambient PM2.5 exposure with fetal BDNF level at birth. The median concentration of BDNF was 13,403 pg/ml. Vaginal deliveries and female infants had higher BDNF levels than cesarean deliveries and male infants. One natural log (ln) unit increase in maternal PM2.5 exposure during the second trimester was significantly associated with − 0.20 (95% CI: −0.36, −0.05) ln-unit decrease in BDNF level in all births. These effects were stronger and more significant in vaginal deliveries and in male infants. Our study suggests that BDNF in the cord blood may serve as a potential biomarker in assessing the neurodevelopmental effects of maternal PM2.5 exposure.

Blood levels of brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE): a systematic review and meta-analysis

ObjectivesBDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE.MethodsWe searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle–Ottawa scale was used to assess the quality of the included publications, and statistical analyses were carried out using R 4.0.4.ResultsThe final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [ − 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [ − 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R2 were 26.89%, 16.53%, 18.8%, and 49.96%, respectively).ConclusionIn conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies.

Brain-derived neurotrophic factor (BDNF) variants and promoter I methylation are associated with prolonged nocturnal awakenings in older adults.

Brain-derived neurotrophic factor (BDNF) is important for sleep physiology. This study investigates whether BDNF variants and promoter I methylation may be implicated in sleep disturbances in older adults. Genotyping was performed for seven BDNF single nucleotide polymorphisms (SNPs) in 355 community-dwelling older adults (aged ≥65 years) and BDNF exon 1 promoter methylation was measured in blood samples at baseline (n=153). Self-reported daytime sleepiness and insomnia, ambulatory polysomnography measures of sleep continuity and architecture, and psychotropic drug intake were assayed during follow-up. Logistic regression adjusted for age, sex, comorbidities, body mass index, and psychotropic drug intake. Associations were found specifically between wake time after sleep onset (WASO) and four SNPs in the participants not taking psychotropic drugs, whereas in those taking drugs, the associations were either not significant (rs6265 and rs7103411) or in the reverse direction (rs11030101 and rs28722151). Higher BDNF methylation levels were found at most CpG units in those with long WASO and this varied according to psychotropic drug use. The reference group with short WASO not taking drugs showed the lowest methylation levels and the group with long WASO taking treatment, the highest levels. Some SNPs also modified the associations, the participants carrying the low-risk genotype having the lower methylation levels. This genetic and epigenetic study demonstrated blood BDNF promoter methylation to be a potential biomarker of prolonged nocturnal awakenings in older people. Our results suggest the modifying effect of psychotropic drugs and BDNF genetic variants in the associations between methylation and WASO.

A Study on the Effect of Traditional Chinese Exercise Combined With Rhythm Training on the Intervention of Older Adults With Mild Cognitive Impairment.

To examine the effect of combination exercise program on cognitive function of older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions. Subjects were 42 older adults (ages, 60-80years) with MCI. The subjects were randomly classified to traditional Chinese exercise combined with rhythm training group (TCE + RTG, n = 14), walking group (WG, n = 14), and control group (CG, n = 14), according to their level of MMSE scores. These groups exercised for 60minutes at 1 session, 3 sessions a week for 12weeks. The intervention program was conducted under multitask conditions to stimulate attention and memory, and the control group attended 3 education classes. Measurements were administered before, after the 6-week, and after the 12-week intervention period; Measurements: The Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), Activities of Daily Living Scale (ADL), and the 17-item Hamilton Depression Scale (HAMD-17), along with the brain-derived neurotrophic factor (BDNF). A repeated-measures analysis of variance was used to examine differences among the 3 groups and between the 3 testing times (pre-test vs middle-test vs post-test). (1) The TCE + RTG showed significant improvement in the MMSE, MoCA, SDMT, and ADL scale test results (P < .01) and HAMD-17 scale test results (P < .05). The WG also showed significant improvement in the MMSE, MoCA, and HAMD-17 scale test results (P < .05) and the ADL scale test results (P < .01). While there was no significant change in the CG after the intervention. (2) The TCE + RTG and WG showed positive improvement in peripheral blood BDNF levels, while the CG showed a decrease in these test results. There were significant differences between the TCE + RTG and CG before and after the intervention. The results suggested that a TCE + RT is beneficial for improving memory and maintaining general cognitive function and peripheral blood BDNF levels in older adults with MCI. Peripheral blood BDNF levels may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of TCE + RT on cognitive function in older adults with MCI. Trial Registration: ChiCTR2200058545, Registered 10 April 2022.

Serum brain-derived neurotrophic factor and macular perfusion in type 2 diabetes mellitus using optical coherence tomography angiography

PURPOSE: To investigate the relationship between serum brain-derived neurotrophic factor (BDNF) and changes in macular perfusion in different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: The study was conducted on 72 eyes of people with type 2 diabetes mellitus (DM). They were divided into five groups based on their DR stage: no DR (nDR), mild and moderate nonproliferative DR, severe nonproliferative DR, active proliferative DR (aPDR), and stable PDR. The presence or absence of diabetic maculopathy was also used to categorize the cases. All patients underwent a complete history, ophthalmological examination, OCTA imaging, and evaluation of BDNF and glycated hemoglobin A1c levels. RESULTS: The mean blood BDNF levels in the aPDR group were considerably lower than those in the nDR group (P = 0.023). In comparison to eyes without maculopathy, eyes with maculopathy had considerably decreased mean blood BDNF levels (P = 0.0004). Comparing NPDR and PDR groups to nDR as well as NPDR and PDR, a substantial decrease in average and parafoveal vessel density (VD) of the retina and choriocapillaries was seen (P = 0.02). The Foveal Avascular Zone (FAZ) acircularity index and VD were found to be significantly impacted by deteriorating DR (P = 0.001 and 0.017, respectively). It was discovered that there is a positive correlation between BDNF and the FAZ fractal dimension (P = 0.03). In diabetic eyes, there was a statistically favorable correlation between BDNF levels and best corrected visual acuity (P = 0.002). Furthermore, there was a negative relationship between DM duration and BDNF (P = 0.021). CONCLUSION: Serum BDNF levels decreased with the progression of DR and in patients with maculopathy. BDNF was found to be related to macular perfusion, particularly in the fovea.

Reduced Cortical Thicknesses of Adolescents with Bipolar Disorder and Relationship with Brain-derived Neurotrophic Factor.

Cortical thickness (CT) and brain-derived neurotrophic factor (BDNF) were widely investigated in bipolar disorder (BD). Previous studies focused on the association between the volume of subcortical regions and neurotrophic factor levels. In this study, we aimed to evaluate the association of the CT in youth with early-onset BD with BDNF levels as a potential peripheral marker of neuronal integrity. Twenty-three euthymic patients having a clinical diagnosis of BD and 17 healthy subjects as an age-matched control group with neuroimaging and blood BDNF levels were found eligible for CT measurement. A structural magnetic resonance scan (MRI) and timely blood samples were drawn. Youth with BD exhibited lower cortical thickness in caudal part of left (L) middle frontal gyrus, right (R) paracentral gyrus, triangular part of R inferior frontal gyrus, R pericalcarine region, R precentral gyrus, L precentral gyrus, R superior frontal gyrus and L superior frontal gyrus when compared to healthy controls. The effect sizes of these differences were moderate to large (d=0.67-0.98) There was a significant correlation between BDNF levels with caudal part of the R anterior cingulate gyrus (CPRACG) in adolescents with BD (r=0.49, p=0.023). As a special region for mood regulation, the CT of the caudal part of the R anterior cingulate gyrus had a positive correlation with BDNF. Regarding the key role of CPRACG for affective regulation skills, our results should be replicated in future follow-up studies, investigating a predictive neuroimaging biomarker for the early-onset BD.

Association of serum brain-derived neurotrophic factor with hepatic enzymes, AST/ALT ratio, and FIB-4 index in middle-aged and older women.

Substantial evidence suggests an important role of liver function in brain health. Liver function is clinically assessed by measuring the activity of hepatic enzymes in the peripheral blood. Brain-derived neurotrophic factor (BDNF) is an important regulator of brain function. Therefore, we hypothesized that blood BDNF levels are associated with liver function and fibrosis. To test this hypothesis, in this cross-sectional study, we investigated whether serum BDNF concentration is associated with liver enzyme activity, aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio, and fibrosis-4 (FIB-4) index in middle-aged and older women. We found that serum BDNF level showed a significant positive association with ALT and γ-glutamyltranspeptidase (GGT) activity and negative association with FIB-4 index, and a trend of negative association with the AST/ALT ratio after adjustment for age. Additionally, these associations remained statistically significant even after adjustment for body mass index (BMI) and fasting blood glucose level. These results demonstrate associations of serum BDNF levels with liver enzymes and hepatic fibrosis-related indices, which may underlie liver-brain interactions.

Reduced plasma BDNF concentration and cognitive decline in veterans with PTSD

Post-traumatic stress disorder (PTSD) is a trauma and stress related disorder frequently associated with cognitive decline. War veterans with PTSD have a higher risk of developing dementia than healthy subjects. Brain derived neurotrophic factor (BDNF) is an important protein that modulates plasticity, memory consolidation and cognitive processes. Lower circulating BDNF levels were related to memory impairment and cognitive deterioration. The aim of this study was to evaluate cognitive deterioration and plasma BDNF concentration in 120 veterans with combat related PTSD, 120 healthy controls, 47 subjects with mild cognitive impairment (MCI) and 76 patients with Alzheimer's disease (AD), and to assess if plasma BDNF concentration might be used as biomarker of cognitive deterioration. Veterans with PTSD had significantly decreased plasma BDNF concentration and worse cognitive performances (assessed using the Mini Mental State Examination, Clock Drawing test and Montreal Cognitive Assessment scores/categories) than healthy subjects, and similarly reduced plasma BDNF and cognitive decline as MCI subjects. Reduced plasma BDNF was found in cognitively impaired subjects. These results suggest that veterans with PTSD should be closely monitored in order to early detect and predict cognitive worsening and promote interventions that might help restore blood BDNF levels and cognitive functions.