Serum Brain-derived Neurotrophic Factor Levels Research Articles

The evaluation of serum brain-derived neurotrophic factor and neurofilament light chain levels in patients with obstructive sleep apnea syndrome.

ObjectivesThis study aimed to compare serum levels of brain‐derived neurotrophic factor (BDNF) and neurofilament light (NfL) chain in normal individuals and patients with mild and moderate‐severe obstructive sleep apnea syndrome (OSAS).MethodsWe enrolled 81 subjects referred to Otorhinolaryngology (Ear‐Nose‐Throat), Gazi University Faculty of Medicine, between 2017 and 2019. Based on the severity of OSAS, patients were divided into three groups: group 1 with mild OSAS (apnea‐hypopnea index [AHI] 5‐15; n = 26), group 2 with moderate‐severe OSAS (AHI > 15; n = 32), and group 3 with normal individuals (AHI scores < 5; n = 23).ResultsSerum NfL and BDNF levels were evaluated together with the clinical data for all subjects. Significant differences were seen in the oxygen desaturation index (ODI), apnea index, hypopnea index, sleep efficiency, and NfL levels (P < .05) between the three groups. In the moderate‐severe group, NfL levels showed a significant positive correlation with apnea index (P < .05, r = .389), hypopnea index (P < .05, r = .455), and ODI (P = .04; r = .362).ConclusionsOur findings clarify the pathophysiology of OSAS in cases of repetitive hypoxia and chronic neuronal damage. Based on our results, we recommend that in addition to BDNF, NfL should also be evaluated in different and larger patient cohorts.

Neuromodulatory effects of Transcranial Pulsed Current Stimulation (tPCS) in Fibromyalgia: protocol for a double-blinded, sham-controlled, randomized clinical trial

Fibromyalgia (FM) is a functional syndrome characterized by musculoskeletal, diffuse and persistent (&gt; 3 months) chronic pain, that is also characterized by sleep disturbances, fatigue, humor changes and cognitive and psychological changes. Transcranial Pulsed Current Stimulation (tPCS) is a new Transcranial Electrical Stimulation (tES) that has been studied as a treatment option for chronic pain and neurological conditions . Studies have shown that tPCS is capable of pain and cognitive modulation; however, there are not enough studies with evidence of its efficacy.Therefore, the primary aim of this study is to evaluate the effects of tPCS in pain, evaluated through Visual Analogue Scale (VAS) in FM patients; besides that, it is aimed to evaluate the effects of tPCS on quality of life, cognitive impairments, pain pressure threshold, descending inhibitory system of pain, and serum levels of Brain Derived Neurotrophic Factor (BDNF) and S100 Calcium-Binding Protein B (S100B). A randomized, double-blinded, controlled with sham clinical trial will be conducted with 70 (Critical f: 2.003; ES: 0.76; alpha: 0.05; power: 0.80) women with Fibromyalgia, from 30 to 65 years with pain on the Visual Analogue Scale (VAS) higher than 6 in the last 3 months. All patients will read and sign an Informed Consent Form (ICF). Each patient will be randomized to either 1+4 sessions of tPCS (2mA, 6-10Hz, 1-20ms, 20-25 minutes) or Sham. Patients will complete the following questionnaires/tests: Visual Analogue Scale (VAS), Pittsburgh Sleep Quality Index (PSQI), Fibromyalgia Impact Questionnaire (FIQ), Pain Catastrophizing Scale (PCS), Profile of Chronic Pain (PCP), Conditioned Pain Modulation Task (CPM-T), Pain Pressure Threshold Task (PPT-T), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and blood collection for serum levels of BDNF and S100B. For the main outcome, comparison between variables during time will be made through linear regression, with an adjustment for baseline levels and possible confounders.

BDNF blood serum linkage with BDNF gene polymorphism (rs6265) in thyroid pathology patients in the West-Ukrainian population.

Objective. Brain-derived neurotrophic factor (BDNF) is identified as an important growth factor involved in learning and memory. Patients with Hashimoto's thyroiditis can suffer from cognitive dysfunction, whereas BDNF is directly regulated by thyroid hormones. It seems reasonable to propose that changes in BDNF expression underlie some of the persistent neurological impairments associated with hypothyroidism. Methods. The study involved a total of 153 patients with various forms of thyroid pathology. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay with highly sensitive Human BDNF ELISA Kit. Genotyping of the BDNF (rs6265) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System. Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions. Results. Distribution rs6265 variants in the patients depending on the different types of thyroid pathology showed no significant difference in the relative frequency of BDNF polymorphic variants. Presence of hypothyroidism, regardless of its cause (autoimmune or postoperative), there was a decrease in the serum BDNF levels in all genotypes carriers compared with the control group. The analysis of the correlation between BDNF levels and the levels of thyroid-stimulating hormone (TSH), thyroxine (T4), anti-thyroglobulin (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibodies showed a significant inverse relationship between BDNF and TSH levels (p<0.001), a direct correlation between BDNF and T4 levels in the blood (p<0.001), and a weak direct relationship between anti-Tg and BDNF levels (p=0.0157). Conclusion. The C allele presence is protective and associates with the lowest chances for reduced serum BDNF levels in thyroid pathology patients in the West-Ukrainian population. However, the T-allele increases the risk of low BDNF levels almost 10 times in observed subjects.

The role of tropomyosin receptor kinase type B in modulation of neuropathic pain in diabetic polyneuropathy

It is well known that brain derived neurotrophic factor (BDNF) can modulate pain symptoms in diabetic polyneuropathy (DPN). It is still not known which type of receptor mediates its hyperalgesic effects. Aim: to compare serum levels of BDNF and tropomyosin receptor kinase type B (trkB) in patients with a painful and painless forms DPN.

Effect of Methadone Maintenance on Expression of BDNF and CREB Genes in Brain VTA of Male Morphine Treated Rats.

Morphine independently reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats. In this study, 24 Wistar rats (200-250g) were assigned to three experimental groups: 1) Animals without morphine treatment (control); 2) Morphine treated animals (10 mg/kg, twice/day through subcutaneous injection for 21 days); 3) Animals under methadone maintenance after treatment with morphine (maintenance dose of methadone was achieved during 14 days equal to 1 mg per 100 ml at the first week and 2.5 mg per 100 ml at second week). To evaluate the expression of BDNF and CREB genes, real time PCR method was used, and ELISA was applied to measure the serum level of BDNF protein at the end of the experiment. According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to a significant reduction in the expression of BDNF and CREB genes at VTA as well BDNF serum level compared with the control group. It was concluded that methadone, like morphine, causes a significant reduction in the expression of BDNF and CREB genes in the brain VTA area of rats as well as BDNF serum level compared with the control group.

Negative Correlation between Serum Brain-derived Neurotrophic Factor Levels and Obesity Predictor Markers and Inflammation Levels in Females with Obesity

BACKGROUND: Obesity has been widely associated with structural and functional changes in the brain, whereas inflammation is one of the potential mechanisms involved in these changes.&#x0D; OBJECTIVE: This study aims to prove the relationship between serum brain-derived neurotrophic factor (BDNF) levels and obesity predictor markers (body mass index and waist to hip ratio) and inflammation (interleukin-6 and Tumor Necrosis Factor-alpha) levels in females with obesity.&#x0D; METHODS: This study used a cross-sectional study method using 33 females with obesity aged 19-23 years, body mass index (BMI) &gt; 27.5 kg/m2, normal blood pressure, normal resting heart rate (RHR), normal hemoglobin (Hb), and fasting blood glucose (FBG) ≤ 100 mg/dL. The examination of serum BDNF, IL-6, and TNF-α levels using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The data were analyzed using Pearson product-moment test with a significant levels p&lt;0.05.&#x0D; RESULTS: The results indicated that there is a negative correlation between serum BDNF levels and BMI (r = –0.759; p&lt;0.001), WHR (r = –0.675; p&lt;0.001), IL-6 levels (r = –0.530; p&lt;0.001) and TNF-α levels (r = –0.561; p&lt;0.001).&#x0D; CONCLUSION: Based on the results of the study, there is a negative correlation between serum BDNF levels and BMI, waist to hip ratio, and inflammation (interleukin-6 and Tumor Necrosis Factor-alpha) levels in females with obesity. Further studies are needed to confirm the present findings.

Serum and aqueous humor levels of brain-derived neurotrophic factor in patients with primary open-angle glaucoma and normal-tension glaucoma.

This study was designed to compare the levels of brain-derived neurotrophic factor (BDNF) in the serum and aqueous humor (AH) of patients with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). This prospective, observational study consists of 30 patients with POAG, 30 patients with NTG, and 30 healthy controls. The serum and AH BDNF levels were assessed using an enzyme-linked immunosorbent assay. BDNF levels in serum and AH were markedly lower in the glaucoma groups (POAG and NTG) than in the control group (p <0.05). When comparing the NTG and POAG groups, the average serum BDNF level was significantly lower in the NTG group than in the POAG group (p <0.05). The difference in the mean BDNF levels in AH between the POAG and NTG groups was not statistically significant. (p = 0.538). We confirmed that serum BDNF levels were lower in patients with NTG than in those with POAG. BDNF could be a causative systemic biomarker in NTG.

Brain-derived neurotrophic factor in autoimmune inflammatory diseases (Review).

Numerous recent studies reported that brain-derived neurotrophic factor (BDNF) also exists in the peripheral blood to regulate the proliferation, differentiation and survival of lymphocytes. Besides the role of BDNF in neuron repair, circulatory BDNF also enhances the proliferation and reduces apoptosis of lymphocytes. Peripheral lymphocytes express both BDNF and its receptors. Increasing evidence has indicated that altered BDNF serum levels significantly affect patients with autoimmune inflammatory diseases and may also be linked to the pathogenesis of diseases. For instance, systemic lupus erythematosus, an autoimmune inflammatory disease involving multiple organs, is frequently linked to altered B lymphocyte function, imbalance of T-cell subpopulations and loss of immune tolerance, which dysregulates the immune regulatory network with excessive secretion of inflammatory cytokines. The present review summarized studies that suggest a potential link between circulatory BDNF and autoimmune inflammatory diseases.

Genetic association between bone mineral density and the fracture of distal radius: A case-control study.

Low bone mineral density (BMD) was significantly related to the fracture of distal radius. Serum brain-derived neurotrophic factor (BDNF) level was closely related to BMD in spine and osteoporotic fractures. In this study, we aimed to explore the association of BDNF polymorphisms (rs6265 and rs7124442) with BMD and the fracture of distal radius.This retrospective study included 152 patients with distal radius fractures and 148 healthy controls. BDNF polymorphisms were detected via TaqMan allelic discrimination assay. BMD was evaluated through X-ray. Difference in features between cases and controls were compared adopting Chi-square test or t test. The associations of BDNF polymorphisms with fracture risk of distal radius and BMD were assessed employing χ2 test and expressed by odd ratios (ORs) with 95% confidence intervals (95% CIs).BMD was significantly decreased in patients with the fracture of distal radius than in healthy controls. The polymorphism rs6265 significantly increased the risk of distal radius fracture (adjustment: GA: OR = 1.724, 95%CI = 1.003 –2.951, P = .049; GG: OR = 2.415, 95%CI = 1.0219 –3.674, P = .005). Moreover, rs6265 genotypes GA (OR = 4.326, 95%CI = 1.725 –11.896, P = .003) and GG (OR = 13.285, 95%CI = 3.659 –51.072, P = .001) significantly increased BMD reduction. However, BDNF polymorphism rs7124442 had no obvious correlation with BMD or fracture risk.BMD was associated with BDNF rs6265 polymorphism. BDNF polymorphism rs6265 could elevate the risk of osteoporosis and distal radius fracture.

The association between BDNF levels and risperidone-induced weight gain is dependent on the BDNF Val66Met polymorphism in antipsychotic-naive first episode schizophrenia patients: a 12-week prospective study

A growing number of studies have shown that brain-derived neurotrophic factor (BDNF) is associated with weight gain during antipsychotic treatment in schizophrenia patients. However, there is still a lack of research results in the initial stage of antipsychotic treatment. This study aimed to evaluate the relationship between weight gain caused by risperidone monotherapy for 12 weeks and BDNF level in antipsychotic-naive and first-episode (ANFE) patients with schizophrenia, and we hypothesize that this may depend on BDNF Val66Met gene polymorphism. In a 12-week longitudinal trial, 225 ANFE patients were enrolled and treated with risperidone. Body weight was measured at baseline and during the 12-week follow-up. After treatment, the average weight of ANFE patients increased by 2.6 kg. Furthermore, we found that in patients with Val/Val genotype, the increase in serum BDNF levels was negatively correlated with risperidone-induced weight gain (r = −0.44, p = 0.008). Regression analysis showed that the baseline BDNF level was a predictor of weight gain after treatment (β = −0.45, t = −3.0, p = 0.005). Our results suggest that the BDNF signaling may be involved in weight gain caused by risperidone treatment. Furthermore, the negative association between weight gain and increased BDNF levels during risperidone treatment in ANFE schizophrenia depends on the BDNF Val66Met polymorphism.

BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization

Background:Brain-derived neurotrophic factor (BDNF) influences brain plasticity and feeding behaviour, and it has been linked to anorexia nervosa in numerous studies. Findings in mostly adult patients point to reduced serum BDNF levels in the acute stage of anorexia nervosa and rising levels with weight recovery. However, it is unclear whether this increase leads to normalization or supranormal levels, a difference that is potentially important for the etiology of anorexia nervosa and relapse.Methods:We measured serum BDNF at admission (n = 149), discharge (n = 130), 1-year follow-up (n = 116) and 2.5-year follow-up (n = 76) in adolescent female patients with anorexia nervosa hospitalized for the first time, and in healthy controls (n = 79). We analyzed associations with body mass index, eating disorder psychopathology and comorbidities.Results:Serum BDNF was only nominally lower at admission in patients with anorexia nervosa compared to healthy controls, but it increased continuously and reached supranormal levels at 2.5-year follow-up. BDNF was inversely associated with eating disorder psychopathology at discharge and positively associated with previous weight gain at 1-year follow-up.Limitations:We compensated for attrition and batch effects using statistical measures.Conclusion:In this largest longitudinal study to date, we found only nonsignificant reductions in BDNF in the acute stage of anorexia nervosa, possibly because of a shorter illness duration in adolescent patients. Supranormal levels of BDNF at 2.5-year follow-up could represent a pre-existing trait or a consequence of the illness. Because of the anorexigenic effect of BDNF, it might play an important predisposing role for relapse and should be explored further in studies that test causality.

Association between Serum Brain-derived Neurotrophic Factor and 25-OH Vitamin D Levels with Vitamin D Receptors Gene Polymorphism (rs2228570) in Patients with Autoimmune Thyroiditis and Hypothyroidism

BACKGROUND: Different polymorphisms in Vitamin D receptors (VDRs) have an important role in autoimmune thyroiditis (AIT) risk. Hashimoto’s thyroiditis (HT) is the most recurrent autoimmune thyroid disorder. Patients with HT may suffer from cognitive impairment brain-derived neurotrophic factor (BDNF) which has been identified as an important growth factor that is involved in learning and memory. AIM: This study examined the linkage of VDR gene polymorphism (rs2228570) with blood serum levels of BDNF and 25-OH Vitamin D in thyroid pathology of patients in the West Ukrainian population. METHODS: This research is a case–control study was performed in HSEEU “Bukovinian State Medical University,” Chernivtsi Regional Endocrinology Center, and I. Horbachevsky Ternopil National Medical University, Ukraine, from September 2017 to December 2020. The study involved a total of 153 patients with post-operative hypothyroidism, hypothyroidism induced by AIT, and patients with both AIT and elevated serum antibodies anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay (ELISA) with highly sensitive Human BDNF ELISA Kit. Genotyping of the VDR (rs2228570) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™ Real-Time Polymerase Chain Reaction (PCR) Detection System (Bio-Rad Laboratories, Inc., USA). PCR for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). RESULTS: Our study revealed a significant decrease in the BDNF level in the study group in carriers of the AA and AG genotypes by 1.58 and 2.39 times, corresponding, compared with carriers of the AA genotype in the control group. Concurrently, there was no significant difference in the BDNF level between different genotypes of VDR rs2228570 in the research group. In our study, analysis of the correlation between serum BDNF levels and 25-OH Vitamin D concentration shows a moderate direct relationship (r = 0.4) between BDNF and 25-OH Vitamin D (p = 0.006). CONCLUSIONS: The rs2228570 VDR polymorphism is not a risk factor for decreased serum BDNF levels. At the same time, our study found a moderate direct relationship between serum BDNF levels and 25-OH Vitamin D.

Comparison of serum BDNF, IL-1β, IL-6, TNF-α, CRP and leucocyte levels in unipolar mania and bipolar disorder.

Unipolar mania is not included in the diagnostic and statistical manual of mental disorders-5 (DSM-5) as a separate diagnosis, although it is defined by widely accepted diagnostic criteria. The aim of this study was to investigate the differences between unipolar mania and bipolar disorder in terms of clinical and inflammatory parameters. The data of 495 hospitalised patients with bipolar disorder diagnoses were analysed retrospectively. Forty met the diagnostic criteria for unipolar mania. Two patients refused to participate in the study. Thirty-eight unipolar mania patients and 42 randomly selected patients with bipolar disorder diagnosis were included in the study. The two groups were compared in terms of sociodemographic, clinical characteristics, serum brain-derived neurotrophic factor, C-reactive protein (CRP), leucocyte and cytokine levels. A total of 40 (8.08%) of 495 patients diagnosed with bipolar disorder met the unipolar mania diagnostic criteria. The number of manic episodes and the number of hospitalisations were statistically higher in the unipolar mania group than in the bipolar disorder group. Among all the manic symptoms, the incidence of symptoms such as euphoria, increased sexual interest, grandiosity and delusions were found to be statistically higher in the unipolar mania group. Interleukin (IL)-6 and CRP levels were significantly higher in the unipolar mania group than in the bipolar disorder group. Unipolar mania differs from bipolar disorder in terms of clinical features and serum IL-6 and CRP levels.

Brain-Derived Neurotrophic Factor (BDNF) Levels In Relation To Depression In Egyptian Diabetic Women: A Pilot Study

Background: Brain-derived neurotrophic factor (BDNF) is a crucial moderator of neuronal plasticity in adults, a potential association between BDNF and depression has been reported. Besides BDNF plays a role in glucose and energy metabolism. Methods: This work included 180 women (25-55 years old). Ninety diabetic patients with the clinical diagnosis of depression and 90 were normal controls. Plasma BDNF was evaluated using ELISA. The Zung Self‑Rating Depression Scale (SDS) consisting of 20 objects with a Likert‑type scale after each was used. HbA1c were measured in each patient using a clinical auto-analyzer. Results: BDNF levels in serum decreased significantly in diabetic depressed women compared to controls. Moreover, BDNF levels were inversely proportional to age, BMI, HbAc1 and LDL.Conclusion: The study suggests that age, BMI, HbAc1 have a definite impact on the circulating levels of BDNF in peripheral blood. The outcomes delineate that BDNF could participate in glucose impairment and lipid metabolism in diabetic patients.

Brain-derived neurotrophic factor in relation to central obesity in children with sleep disordered breathing.

IntroductionSleep disordered breathing (SDB) represents common comorbidities of childhood obesity leading to interrupted sleep and sleep deprivation. Sleep deprivation alters secretion of brain-derived neurotrophic factor (BDNF), which is an appetite regulator. However, little is known about the relation between BDNF and central obesity in children with SDB. The aim of the study was to evaluate BDNF level and anthropometric indices in relation to SDB in children with obesityMaterial and methodsA prospective case-control study was conducted on 30 children with obesity (BMI > 95th percentile) and 30 healthy lean children (BMI 5th-85th percentile). Polysomnographic, anthropometric data and BDNF serum level were obtained from all included children. Serum level of BDNF and anthropometric indices of obesity were assessed in relation to SDB in children with obesity. Regression analysis was done to determine predictors for SDB in children with obesity.ResultsIn comparison to healthy controls, anthropometric indices of central obesity were significantly higher while BDNF was significantly lower in obese children, especially those with SDB. Respiratory disturbance index has a significant positive correlation with anthropometric indices of central obesity and a significant negative correlation with BDNF level. Central obesity and decreased BDNF were associated with 2-fold increased risk for SDB. Waist circumference/height ratio and neck circumference/height ratio have 89.5%, 75% sensitivity and 81.23%, 84.62% specificity at a cutoff point > 0.62, > 0.24 respectively for prediction of SDB in children with obesity.ConclusionsCentral obesity and decreased BDNF represent independent predictors for SDB in children with obesity. Anthropometric indices adjusted to height are a simple screening tool for SDB in obese children.

Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults.

Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC).Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days.Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF.Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health.Clinical Trial Registration:ClinicalTrials.gov, NCT03904433.

Association between the improvement in depressive symptoms and serum BDNF levels in drug-naive first episode patients with schizophrenia: A longitudinal follow-up

Depressive symptoms are frequent clinical manifestations in patients with schizophrenia. Decreased brain-derived neurotrophic factor (BDNF) has been shown to be involved in the development of depressive symptoms. However, the detailed molecular mechanism of BDNF in the depressive symptoms of schizophrenia patients remains to be fully elucidated. This study aimed to investigate the role of BDNF in the depressive symptoms in drug-naïve first-episode (DNFE) patients with schizophrenia and whether BDNF levels were associated with the improvement of depressive symptoms after olanzapine treatment. 50 DNFE schizophrenia patients and 55 healthy controls were recruited, and their serum BDNF levels were compared. All patients were treated with olanzapine monotherapy for 12 weeks, and 45 patients completed the trial. The serum BDNF levels and depressive symptoms were measured again at follow-up. We found that DNFE patients had lower BDNF levels, compared to controls. Last observation carried forward (LOCF) analysis was used for patients who dropped out after the second month, and 50 patients were included in the statistical analysis with LOCF. After 12 weeks of treatment with olanzapine, BDNF levels were significantly increased and depressive symptoms were significantly decreased. Correlation analysis showed that the change of BDNF levels after treatment was correlated with the change of HAMD total score from baseline. Further regression analysis showed that the change in BDNF levels was an independent predictor for the improvement in depressive symptoms, after controlling age, BMI change and the decrease of PANSS total score. However, the baseline BDNF levels were not associated with an improvement in depressive symptoms in patients. Our findings reveal that olanzapine treatment can increase BDNF levels and improve depressive symptoms in schizophrenia patients. Moreover, the changes in serum BDNF levels were related to the improvement in depressive symptoms.

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.

Improving Clinical, Cognitive, and Psychosocial Dysfunctions in Patients with Schizophrenia: A Neurofeedback Randomized Control Trial.

Objectives The aim of this study was to use neurofeedback (NF) training as the add-on therapy in patients with schizophrenia to improve their clinical, cognitive, and psychosocial condition. The study, thanks to the monitoring of various conditions, quantitative electroencephalogram (QEEG) and brain-derived neurotrophic factor (BDNF), was supposed to give an insight into mechanisms underlying NF training results. Methods Forty-four male patients with schizophrenia, currently in a stable, incomplete remission, were recruited into two, 3-month rehabilitation programs, with standard rehabilitation as a control group (R) or with add-on NF training (NF). Pre- and posttherapy primary outcomes were compared: clinical (Positive and Negative Syndrome Scale (PANSS)), cognitive (Color Trails Test (CTT), d2 test), psychosocial functioning (General Self-Efficacy Scale (GSES), Beck Cognitive Insight Scale (BCIS), and Acceptance of Illness Scale (AIS)), quantitative electroencephalogram (QEEG), auditory event-related potentials (ERPs), and serum level of BDNF. Results. Both groups R and NF improved significantly in clinical ratings (Positive and Negative Syndrome Scale (PANSS)). In-between analyses unveiled some advantages of add-on NF therapy over standard rehabilitation. GSES scores improved significantly, giving the NF group of patients greater ability to cope with stressful or difficult social demands. Also, the serum-level BDNF increased significantly more in the NF group. Post hoc analyses indicated the possibility of creating a separate PANSS subsyndrome, specifically related to cognitive, psychosocial, and BDNF effects of NF therapy. Conclusions Neurofeedback can be effectively used as the add-on therapy in schizophrenia rehabilitation programs. The method requires further research regarding its clinical specificity and understanding mechanisms of action.

Curiosity-Based Interventions Increase Everyday Functioning Score But Not Serum BDNF Levels in a Cohort of Healthy Older Adults.

An enriched environment is effective in stimulating learning and memory in animal models as well as in humans. Environmental enrichment increases brain-derived neurotrophic factor (BDNF) in aged rats and reduces levels of Alzheimer-related proteins in the blood, including amyloid-β (Aβ) peptides and misfolded toxic forms of tau. To address whether stimulation of curiosity, which is a form of enrichment, may provide a buffer against Alzheimer’s disease (AD), we measured levels of biomarkers associated with AD at baseline and after a 6-week intervention in older adults (>65 years of age) randomized to one of three different intervention conditions. Specifically, in this pilot study, we tested the effectiveness of a traditional, structured learning environment compared to a self-motivated learning environment designed to stimulate curiosity. There were no significant differences from baseline to post-intervention in any of the groups for Aβ42/Aβ40 ratio or t-tau (total-tau) plasma levels. Serum BDNF levels decreased significantly in the control group. Interestingly, individuals who had the lowest serum BDNF levels at baseline experienced significantly higher increases in BDNF over the course of the 6-week intervention compared to individuals with higher serum BDNF levels at baseline. As expected, older individuals had lower MoCA scores. Years of education correlated negatively with Aβ levels, suggesting a protective effect of education on levels of this toxic protein. ECog scores were negatively correlated with BDNF levels, suggesting that better performance on the ECog questionnaire was associated with higher BDNF levels. Collectively, these findings did not suggest that a 6-week cognitive training intervention focused on curiosity resulted in significant alterations in blood biomarkers but showed interesting correlations between cognitive scores and BDNF levels, further supporting the role of this trophic factor in brain health in older adults.