Brain-derived Neurotrophic Factor Gene Polymorphisms Research Articles

Brain-derived Neurotrophic Factor Level and Gene Polymorphism as Risk Factors for Depression in Patients with type 2 Diabetes Mellitus- A Case-Controlled Study.

Diabetes mellitus and depression are comorbidities that can be caused by each other. Brain-derived neurotrophic factor (BDNF) functions as a neuronal growth factor. It maintains the functional integrity of the nervous system. To study the possible association between BDNF levels and gene polymorphism with depression in patients diagnosed with type 2 diabetes mellitus. The Elisa technique measured BDNF, and rs6265 gene polymorphism was detected using real-time PCR. Depression was assessed utilizing a clinical interview tool designed to establish the diagnosis of depression and differentiate it from other psychiatric diseases. BDNF levels were significantly lower in patients with type 2 diabetes mellitus and symptoms of depression than in patients with type 2 diabetes mellitus and no symptoms of depression (82.6±16.1. Vs 122± 17.47, p˂ 0.001). There was a statistically significant difference in BDNF levels in patients with diabetes among the three genotypes of the BDNF gene (p-value < 0.001). Val/ Val carriers had the highest serum BDNF levels, and Met/ Met carriers had the lowest serum BDNF levels. Subgroup analysis showed statistically significant genotype-related differences in serum BDNF levels among the three subgroups in the Depression group. Val/ Val carriers had the highest serum BDNF levels, and Met/ Met carriers had the lowest serum BDNF levels. BDNF Val66Met polymorphism had no significant association with the presence of depression, yet there was a trend towards significance (p = 0.05) Conclusion: In this pilot, Low levels of BDNF were associated with depression in patients with type 2 diabetes. Carriers of the Met/ Met allele have the lowest serum BDNF levels. Multicenter studies with more participants are required.

The Relationship between the Brain-Derived Neurotrophic Factor Gene Polymorphism (Val66Met) and Substance Use Disorder and Relapse.

Substance addiction is a neuropsychiatric disorder characterized by a recurring desire to continue using a substance despite harmful consequences. Brain-derived neurotrophic factor (BDNF) is a protein that plays a role in the activity-dependent remodeling of neural function in adult nervous systems. This study analyzed the association of the rs6265 polymorphism of the BDNF gene in a group of patients addicted to psychoactive substances who were participating in addiction treatment for the first time, in a group of post-relapse psychoactive substance abusers and in a control group. The study also assessed personality and anxiety in all study groups. Statistically significant differences in the frequency of genotypes and alleles were found between all study groups. Compared to the control, both study groups had statistically significantly higher scores for trait and state anxiety. Addicted patients in both groups also had higher scores on the Neuroticism and Openness scales and lower scores on the Extraversion and Agreeableness scales. The results of this study provide further evidence that personality traits, anxiety and the rs6265 polymorphism of the BDNF gene may be risk factors for susceptibility to addiction to psychoactive substances. In addition, they can be a predictor of addiction relapse, but further extensive studies are required to confirm these findings.

Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker.

Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM. A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI). Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively. Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker's diagnostic and prognostic value should be further investigated in future studies.

Brain-derived neurotrophic factor gene polymorphism affects cognitive function and neurofilament light chain level in patients with subcortical ischaemic vascular dementia.

To investigate the effects of brain-derived neurotrophic factor (BDNF) gene polymorphism on cognitive function, neuroimaging and blood biological markers in patients with subcortical ischaemic vascular dementia (SIVD). A total of 81 patients with SIVD were included. According to their BDNF gene polymorphism, the participants were divided into the Val/Val (n = 26), Val/Met (n = 35), and Met/Met (n = 20) groups. A comprehensive neuropsychological evaluation and multimodal brain MRI scan were performed. MRI markers for small vessel disease were visually rated or quantitatively analysed. Moreover, 52 patients were further evaluated with blood marker assays, including amyloid beta (Aβ), phosphorylated tau at threonine-181 (P-tau181), glial fibrillary acidic protein (GFAP), total tau (T-tau) and neurofilament light chain (NfL). There were no significant differences in demographics, disease duration or MRI markers of small vessel disease between the three groups. Compared with the Val/Val and Val/Met groups, the Met/Met group showed worse performance in the verbal fluency test and higher levels of plasma NfL. The rs6265 polymorphism of the BDNF gene is associated with semantic language fluency in patients with SIVD. The Met genotype may be a risk factor for cognitive impairment and neuronal injury.

Genotyping of Macaque Population on the Brain-Derived Neurotrophic Factor Gene Polymorphism by Mismatch Amplification Mutation Assay (MAMA)-PCR.

Human rs6265 (196G>A) polymorphism in the BDNF gene is associated with many clinically significant phenotypic manifestations. Rhesus monkey (Macaca mulatta) has a functionally significant rs309950446 ( 136G>A) polymorphism. To determine this polymorphism in macaques, we used mismatch amplification mutation assay (MAMA)-PCR method with non-complementary nucleotide to the template chain at the 3rd position from the 3'-end of the allele-specific primers (mismatch primers), which allowed the best discrimination of the alleles. Genotyping of male rhesus monkeys (n=178) and cynomolgus monkeys (Macaca fascicularis) (n=90) was carried out. The A/A, G/G, and G/A genotypes were found in 16, 34, and 50% rhesus macaques, respectively. In the cynomolgus macaques, the mutant polymorphic allele was not detected. The study results allow considering rhesus macaques as a potential biological model for assessment of the gen-environment interaction of the BDNF gene polymorphism.

Association of polymorphisms rs4680 of the Catechol-O-Methyltransferase gene and rs6265 of the brain derived neurotrophic factor gene with the behavioral inhibition and behavioral activation systems

The Behavioral Inhibition System (BIS) comprises limbic circuitry implicated in avoidance behaviors. Its increased activation has been identified as a risk factor for anxiety and depressive disorders. In addition, both Catechol-O-Methyltransferase (COMT) and Brain Derived Neurotrophic Factor (BDNF) have been postulated as candidate genes that constitute a vulnerability for the onset of anxiety and depressive disorders. The aim of this study was to evaluate the possible association between the rs4680 polymorphism of the COMT gene and the rs6265 polymorphism of the BDNF gene with the BIS and the Behavioral Activation System (BAS) in a population sample from Colombia. Genetic information was obtained by extracting DNA from blood samples of 80 participants and using Taqman probes designed for each polymorphism. In addition, participants completed a BIS/BAS scale in order to establish a neuropsychological classification. The frequency of the Met allele of the BDNF gene was greater in the group with BIS sensitivity compared to the group with BAS sensitivity. On the contrary, the frequency of the Met allele of the COMT gen did not show a significant association with the BIS. The rs6265 polymorphism of BDNF gene is associated with the BIS which in turn constitutes a risk factor for anxiety and depression.

BACKGROUND EEG ACTIVITY MEDIATES ASSOCIATIONS BETWEEN BDNF-VAL66MET POLYMORPHISM AND MEMORY DURING AGING

Significant heterogeneity in cognitive aging is explained by the influence of both genetic and environmental factors. BDNF (brain-derived neurotrophic factor) is a neurotropic factor involved in the processes of plasticity in the mature brain. Val66Met polymorphism is a functional polymorphism of the BDNF gene, which determines its association with the architectonics and functions of the brain and the efficiency of cognitive functions. The aim of this study was to identify the aging-related features of the relationship between Val66Met polymorphism and the efficiency of verbal memory processes, determined in the dichotic test, as well as with the background oscillatory activity of the brain, recorded with eyes closed in 52 EEG leads. The study involved 235 right-handed young Caucasians (YA, mean age 21.65 years, SD = 3.18) and 141 older (OA, 64.37 years, SD = 6.04). Genetic differences in memory parameters and endophenotypes of EEG activity were found only in OA individuals. In dichotic testing, subjects with the Val/Val genotype reproduced fewer words from the right ear compared to carriers of the Met allele. When analyzing the EEG, genetic differences were found in the focal indicators of asymmetry in the power of the delta, theta, beta 1 and 2 rhythms, and were due to the greater power of the rhythms in the central temporal sections of the right hemisphere compared to the left hemisphere in Val/Val, with the opposite ratio in carriers of the Met allele. For the beta 2 rhythm, similar differences in asymmetry were also characteristic of the parietal-occipital regions of the hemispheres. It was found that indicators of central temporal asymmetry are mediators in the association between BDNF gene polymorphism and memory efficiency. The data obtained for the first time show age-related differences in the effects of the Val/Met BDNF polymorphism on the efficiency of verbal memory and EEG power and suggest possible relationships between these genotype-associated parameters.

Associations of Plasma BDNF and BDNF Gene Polymorphism with Cardiometabolic Parameters in Thai Children: A Pilot Study.

Childhood obesity is an important public health crisis worldwide. The brain-derived neurotrophic factor (BDNF) has been demonstrated to play a role in controlling energy homeostasis and cardiovascular regulation. To examine brain-derived neurotrophic factor (BDNF) levels and anthropometric-cardiometabolic and hematological parameters in obese and nonobese children and to determine whether two BDNF gene polymorphisms (G196A and C270T) are linked to BDNF levels, obesity, and anthropometric-cardiometabolic and hematological parameters among Thai children. This case-control study included an analysis of 469 Thai children: 279 healthy nonobese and 190 obese children. Anthropometric-cardiometabolic and hematological variables and BDNF levels were measured. Genotyping of BDNF G196A and C270T was performed using the polymerase chain reaction-restriction fragment length polymorphism technique. Children in the obese group had significantly higher white blood cell counts and some cardiometabolic parameters. Although the difference in BDNF level between the nonobese and obese groups was not significant, BDNF level was significantly positively correlated with hematological and cardiometabolic parameters, including blood pressure, triglycerides, and triglycerides and the glucose index. The BDNF G196A polymorphism in children was only associated with decreased systolic blood pressure (p < 0.05), while the BDNF C270T polymorphism was found not to be related to BDNF levels, obesity, or other parameters after adjusting for potential covariates. These findings in Thai children suggest that obesity is associated with increased cardiometabolic risk factors, but not with BDNF levels or the two BDNF polymorphisms studied, while the BDNF G196A polymorphism is a beneficial marker for controlling blood pressure among Thai children.

Pathoclinical associations between panic disorders and the brain-derived neurotrophic factor Val66Met polymorphism: an updated meta-analysis.

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant's association with PD irrespective of the subject's ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.

Relationship between intestinal flora, inflammation, BDNF gene polymorphism and generalized anxiety disorder: A clinical investigation.

Introduction:Understanding factors related to generalized anxiety disorder pathogenesis is critical for elucidating the mechanism and preventing its establishment. Intestinal flora and hereditary factors such as brain-derived neurotrophic factor (BDNF) gene polymorphism may have a role in the development of generalized anxiety disorder. This work explored the relationship between intestinal flora, inflammatory changes and BDNF gene polymorphisms and the occurrence of generalized anxiety disorder.Methods:Forty-eight patients with generalized anxiety disorder and 57 healthy people were included in the study. As the disease group and control group, the polymorphisms of rs10767664 and rs7124442 of the BDNF gene, differences in the distribution of intestinal flora, and changes in inflammatory and immune indicators were analyzed.Results:The distribution of BDNF gene alleles, genotypes and haplotypes in the disease group were different from those in the control group. The levels of TNF-α (P = .000), interleukin-4 (P = .000), interleukin-10 (P = .043) and IgG (P = .008) in patients with generalized anxiety disorder in the disease group were different from those in the control group. The distribution of gut microbes in patients with generalized anxiety disorder in the disease group was different from that in the control group.Conclusion:The onset of generalized anxiety disorder is related to BDNF gene polymorphism, and is accompanied by changes in intestinal flora and inflammatory immune status in the body.

Prediction of the cognitive impairment development in patients with autoimmune thyroiditis and hypothyroidism.

Objective. The aim of the present work is to define the risk factors that can affect the presence of a cognitive impairment and analyze the associations of the brain-derived neurotrophic factor (BDNF) gene polymorphism (rs6265), vitamin D receptor (VDR) gene polymorphism (rs2228570), and N-methyl-D-aspartate (NMDA) receptor gene polymorphism (rs4880213) with the cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukraine population and predict the development of cognitive disorders in these patients. Methods. The study involved 153 patients with various forms of thyroid pathology (hypothyroidism, autoimmune thyroiditis, elevated serum antibodies anti-thyroglobulin and anti-thyroid peroxidase). Cognitive impairment in the examined patients was evaluated based on the results of the Mini-Mental State Examination (MMSE) test. BDNF, GRIN2B, and 25-OH Vitamin D levels in the serum of the patients and healthy individuals were quantified using highly sensitive commercial enzyme-linked immunosorbent assay kits. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA receptor (rs4880213) gene polymorphism was performed using TaqMan probes and Taq-Man 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. Strong direct relationship between the "Level GRIN2B" and cognitive impairments (p=0.006) was established after evaluating the complex model based on the values of the regression coefficient. An increase in the likelihood of cognitive impairment by 24.898-fold (p=0.012) was seen after assessing the effect of the CT rs6265 genotype. In addition, direct relationship between the influence of the TT rs6265 genotype and an increase in the likelihood of cognitive impairment by a factor of 21.734 (p=0.024) was also established. Conclusion. The present data indicate that the BDNF, TSH, fT4, and vitamin D levels prognostically belong to the significant indicators of the cognitive impairment development.

Brain-Derived Neurotrophic Factor Gene Polymorphism Predicts Response to Continuous Theta Burst Stimulation in Chronic Stroke Patients

ObjectivesThe efficacy of repetitive transcranial magnetic stimulation (rTMS) in clinically relevant neuroplasticity research depends on the degree to which stimulation induces robust, reliable effects. The high degree of interindividual and intraindividual variability observed in response to rTMS protocols, such as continuous theta burst stimulation (cTBS), therefore represents an obstacle to its utilization as treatment for neurological disorders. Brain-derived neurotrophic factor (BDNF) is a protein involved in human synaptic and neural plasticity, and a common polymorphism in the BDNF gene (Val66Met) may influence the capacity for neuroplastic changes that underlie the effects of cTBS and other rTMS protocols. While evidence from healthy individuals suggests that Val66Met polymorphism carriers may show diminished or facilitative effects of rTMS compared to their homozygous Val66Val counterparts, this has yet to be demonstrated in the patient populations where neuromodulatory therapies are most relevant. Materials and MethodsWe examined the effects of BDNF Val66Met polymorphism on cTBS aftereffects in stroke patients. We compared approximately 30 log-transformed motor-evoked potentials (LnMEPs) obtained per time point: at baseline and at 0, 10, 20, and 30 min after cTBS-600, from 18 patients with chronic stroke using single TMS pulses. We used linear mixed-effects regression with trial-level data nested by subject for higher statistical power. ResultsWe found a significant interaction between BDNF genotype and pre-/post-cTBS LnMEPs. Val66Val carriers showed decrease in cortical excitability, whereas Val66Met carriers exhibited a modest increase in cortical excitability for 20 min poststimulation, followed by inhibition 30 min after cTBS-600. ConclusionsOur findings strongly suggest that BDNF genotype differentially affects neuroplastic responses to TMS in individuals with chronic stroke. This provides novel insight into potential sources of variability in cTBS response in patients, which has important implications for optimizing the utility of this neuromodulation approach. Incorporating BDNF polymorphism genetic screening to stratify patients prior to use of cTBS as a neuromodulatory technique in therapy or research may optimize response rates.

Association of serum BDNF level and Val66Met polymorphism with response to treatment in patients of major depressive disease: A step towards personalized therapy

BackgroundMajor depressive disorder (MDD) is one of the most common psychiatric disorders and only less than 50% of MDD patients achieve remission after the first antidepressant trial. Hence, it is important to understand the factors associated with response to various antidepressant medications. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. BDNF and Val66Met polymorphism in the BDNF gene has a role in MDD. This study aimed to determine the association of rs6265 polymorphism and serum BDNF level with response to treatment in MDD patients. MethodsThe study included 200 subjects, consisting of 100 MDD patients treated with oral antidepressants and 50 treated with ECT, and 50 healthy controls. Serum BDNF levels were estimated using ELISA and rs6265 polymorphism was genotyped using tetra-primer ARMS PCR. ResultsVal66Met polymorphism had an association with MDD, and in MDD patients with Met allele was associated with a better response to antidepressants. Serum BDNF level was significantly higher in MDD patients compared to healthy individuals. In MDD patients, lower serum BDNF level was associated with better ECT outcomes. ConclusionsVal66Met polymorphism in BDNF gene and serum BDNF level has the potential to be used as a biomarker for the prediction of response to oral antidepressants and ECT in MDD patients. The presence of the Met allele might be used to predict the chances of occurrence of MDD in the future. The results of our study might form a basis for the development of personalized treatment for MDD in the future.

Interaction between the BDNF gene rs16917237 polymorphism and job stress on job burnout of Chinese university teachers

BackgroundJob burnout is related to both environmental and genetic factors. However, previous studies on job burnout in teachers have mainly focused on potential stressors in the environment, while ignoring genetic factors. Brain-derived neurotrophic factor (BNDF) may be a pathogenic factor involved in burnout symptoms. Therefore, this study further investigated the relationship between the BNDF gene polymorphism, job stress and job burnout in Chinese university teachers. MethodsUsing a cross-sectional design, 361 faculty and staff members from a university in Beijing were enrolled. Job stress was measured with the Work Stress Scale. Job burnout was measured by the Chinese version of the Maslach Burnout Inventory which has three dimensions, namely emotional exhaustion (EE), cynicism (CY), and reduced personal accomplishment (PA). The BDNF gene rs16917237 polymorphism was genotyped in all participants. ResultsCY score was associated with education level (p < 0.01), and PA score was associated with age (p < 0.05). Job stress was positively correlated with EE (r = 0.776), CY (r = 0.457), and PA (r = 0.163) (all p < 0.01). After controlling for gender, age and education level, the BDNF gene rs16917237 polymorphism did not affect job burnout, but it interacted with job stress to influence EE and CY (both p < 0.05), indicating that individuals with TT genotype were more susceptible to higher levels of job stress, resulting in job burnout symptoms. ConclusionsOur results suggest that the BDNF gene rs16917237 TT genotype may be a risk factor for job burnout in Chinese university teachers.

BDNF gene polymorphisms predicting treatment response to CBT-based rehabilitation of depression

Genetic factors were shown to play a major role in both variation of treatment response and incidence of adverse effects to medication in affective disorders. Nevertheless, there is still a lack of therapygenetic studies, investigating the prediction of psychological therapy outcomes from genetic markers. Neuroplasticity and one of its mediators, brain-derived neurotrophic factor (BDNF), are potential research targets in this field.We aimed to investigate Tag SNP polymorphisms of the BDNF gene in depressed patients treated with cognitive behavioral therapy (CBT) in the context of a standardized 6-weeks outpatient rehabilitation program. Treatment response was assessed calculating the mean differences in BDI-II (Beck Depression Inventory) scores from admission to discharge. Six BDNF SNPs, including the Val66Met polymorphism (rs6265), were genotyped. Both genotypic data and BDI-II-scores at admission and discharge were available for 277 patients. Three SNPs, rs10501087 (p = 0.005, FDRp=0.015), rs11030104 (p = 0.006, FDRp=0.012), and the Val66Met polymorphism (rs6265, p<0.001, FDRp=0.006), were significantly associated with treatment response in depressed patients, even after multiple testing correction using the false discovery rate method (FDRp).We conclude that BDNF might serve as promising genetic marker for treatment response to psychological treatment in depression. However, due to our limited sample size, further studies are needed to disentangle the role of BDNF as potential therapygenetic marker.

A Polymorphism in the BDNF Gene (rs11030101) is Associated With Negative Symptoms in Chinese Han Patients With Schizophrenia.

Objective: This study aimed to investigate the association between brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB) gene polymorphisms and schizophrenia. Methods: This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People’s Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the BDNF gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the CREB gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the BDNF and CREB gene polymorphisms and schizophrenic symptoms. Results: There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p > 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p > 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the BDNF gene (p < 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the BDNF gene (p < 0.05). Conclusion: The BDNF gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.

Association of BDNF Gene (rs6265/G196A) Polymorphism with Depression

Depression affects an individual’s feelings, thoughts, and behavior. It is known as the most common mental illness worldwide with complex origin. The risk factors for depression include both genetic as well as environmental factors. Depression is affecting more than 300 million individuals globally and is categorized as a major cause of the global burden of disease. Several studies demonstrate the involvement of the brain-derived neurotrophic factor (BDNF) gene in the etiology of depressive disorder. This study was designed to assess the association of (rs6265/G196A) polymorphism of the BDNF gene in the pathogenesis of depression. The cross-sectional study was conducted consisting of 357 samples from Rawalpindi, Pakistan. Depression was determined through questionnaire, using DSM-Ⅳ (Diagnostic and Statistical Manual for Mental Disorders-Version Ⅳ). DNA was extracted from the blood samples of study participants. The conventional polymerase chain reaction was performed to amplify the BDNF gene and to detect the frequency of rs6265/ G196A SNP in the samples of subjects under study. Statistical analysis was done using Pearson’s Chi-Squared test. It was observed that the homozygous GG genotype is more prevalent in study subjects than the homozygous AA or heterozygous AG genotypes. However, depression is likely to be more prevalent in AA genotype i.e., 37.8%, less prevalent in AG genotype i.e., 34.0%, and least prevalent in GG genotype i.e., 28.2%. This data shows the A allele of the BDNF gene to be more associated with depression than the G allele, suggesting this polymorphism to be a somewhat potential target for anti-depressants.

BDNF Val66Met Polymorphism Is Associated With Motor Recovery After Rehabilitation in Progressive Multiple Sclerosis Patients.

BackgroundRehabilitation is fundamental for progressive multiple sclerosis (MS), but predictive biomarkers of motor recovery are lacking, making patient selection difficult. Motor recovery depends on synaptic plasticity, in which the Brain-Derived Neurotrophic Factor (BDNF) is a key player, through its binding to the Neurotrophic-Tyrosine Kinase-2 (NTRK2) receptor. Therefore, genetic polymorphisms in the BDNF pathway may impact motor recovery. The most well-known polymorphism in BDNF gene (rs6265) causes valine to methionine substitution (Val66Met) and it influences memory and motor learning in healthy individuals and neurodegenerative diseases. To date, no studies have explored whether polymorphisms in BDNF or NTRK2 genes may impact motor recovery in MS.ObjectivesTo assess whether genetic variants in BDNF and NTRK2 genes affect motor recovery after rehabilitation in progressive MS.MethodsThe association between motor recovery after intensive neurorehabilitation and polymorphisms in BDNF (rs6265) and NTKR2 receptor (rs2289656 and rs1212171) was assessed using Six-Minutes-Walking-Test (6MWT), 10-Metres-Test (10MT) and Nine-Hole-Peg-Test (9HPT) in 100 progressive MS patients.ResultsWe observed greater improvement at 6MWT after rehabilitation in carriers of the BDNF Val66Met substitution, compared to BDNF Val homozygotes (p = 0.024). No significant association was found for 10MT and 9HPT. NTRK2 polymorphisms did not affect the results of motor function tests.ConclusionBDNF Val66Met was associated with walking function improvement after rehabilitation in progressive MS patients. This result is in line with previous evidence showing a protective effect of Val66Met substitution on brain atrophy in MS. Larger studies are needed to explore its potential as a predictive biomarker of rehabilitation outcome.

Association between functional physical capacity and cognitive performance under destabilizing walking conditions in older adults.

Cognitive decline increases the risk of falls in older adults. Understanding the association between cognitive function, functional physical capacity, and falls may help identify targets for fall screening and intervention. This study examined (1) cognitive and functional physical capacity in community-dwelling older adults with and without a history of falls or the presence of brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism (Val/Met), and (2) the association between their cognitive and functional physical capacity, focusing on the cognitive performance during dual-task, challenging walking conditions. Twenty-nine healthy, community-dwelling older adults attended two testing sessions for (1) functional assessments of physical capacity and global cognitive status, and (2) performing four cognitive tasks (visual and auditory Stroop tasks, Clock task, and Paced Auditory Serial Addition Test) during standing and while walking on the treadmill with and without medio-lateral treadmill platform sways. Participants with a fall history had reduced functional reach distance whereas individuals with Val/Met had reduced functional gait assessment (FGA) score compared to their controls. In addition, participants with a fall history or Val/Met showed reduced Clock task performance under dual-task conditions. Among all cognitive tasks, visual-Stroop performance, especially during the perturbed walking conditions, was significantly correlated with more physical capacity items. The performance of the other three cognitive tasks provided complementary information on those items not correlated with visual-Stroop performance. Clock task performance can distinguish fallers from non-fallers as well as older adults with and without the BDNF gene polymorphism. Administering different types of cognitive tasks and under more challenging walking conditions can better reveal the association between cognitive and functional physical capacity in older adults. Fall screening and prevention intervention should integrate cognitive tasks into the functional physical capacity assessment and training regime, and progress to a more challenging condition such as introducing gait or balance perturbations during the assessment or training.

Neuroplasticity Mechanisms and Prospects for Personalized Rehabilitation Strategies in Patients with Motor and Cognitive Impairments

Aim. To highlight the most important areas of research on the problems of rehabilitation after stroke and the prospects for the development of new rehabilitation strategies, taking into account individual characteristics. Neuroplastic outcomes of anemic infarctions are presented by multi-pattern positive processes of synaptogenesis, sprouting, synthesis of neuroprotective proteins, and destructive effects of stress plasticity inducing dystonic disturbances, deterioration of stabilometric parameters and locomotor gait mechanisms with support deterioration [1]. Thus, specialists in neurorehabilitation should know the basics of fundamental neurophysiological processes in the central nervous system, interhemispheric networks of the brain, and optimize rehabilitation programs, taking into account individualized recovery profiles [2]. One of the factors influencing recovery after a stroke is nervous reorganization, which is proportional to the amount of damage [3]. The processes of neuroplasticity are studied from the standpoint of returning to the pre-stroke recovery model (with minor injuries) – forming “optimal” plasticity and compensatory strategies of “destructive” plasticity (with extensive hemispheric injuries). Micro-RNA (miRNA) are understudied in the neuroprotective reaction to cerebral ischemia. Another important modulator of stroke outcomes is the brain-derived neurotrophic factor (BDNF). Processing of the defective BDNF synthesis when the amino acid valine is replaced by methionine (val-met) that occurs during allelic disorders is of outstanding interest. Conclusion. Promising research areas for strategic approaches to rehabilitation after a stroke are the study of hemispheric introduction, miRNA and neuroprotection cascades; BDNF as an inducer of neuronal differentiation. Allelic BDNF polymorphisms induce lower recovery potential after stroke. Under certain environmental conditions motor learning can overcome the neuroplasticity deficit in the BDNF gene polymorphism. The studies have shown general patterns of positive effects of aerobic stimuli with enhanced BDNF secretion in the recovery of patients with cognitive and motor impairments; nevertheless, the onset period, intensity, duration and exercises rhythmicity have not been established in cerebral stroke. Future studies are likely to optimize rehabilitation profiles based on genetic characteristics.