Brain-derived Neurotrophic Factor Polymorphism Research Articles

Association of BDNF polymorphism with gestational diabetes mellitus risk: a novel insight into genetic predisposition.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy with potential long-term health implications for the mother and child. The interplay between genetics and GDM susceptibility remains an area of active research. Recently, brain-derived neurotrophic factor (BDNF) was investigated in relation to obesity and impaired glucose metabolism and pathogenesis. We aimed to investigate the association of common BDNF polymorphisms, with GDM risk in Israeli females. A cohort of 4,025 Israeli women data for BDNF common SNPs was analyzed for potential association with GDM using binary logistic regressions analysis (SPSS 29.0 and R) adjusted for confounding variables (age, T1DM, T2DM, PCOS) under different genetic models. The GDM and Non-GDM genetic frequencies for the BDNF rs925946 Tag-SNP were significantly different. The genetic frequencies were 54.16 %, and 66.91 % for the wild type (GG), 38.88 and 29.64 % for the heterozygotes (TC), and 6.94 and 3.48 % for the risk allele homozygotes (TT) for the GDM non-GDM populations, respectively. Carriers of BDNF rs925946 were significantly associated with higher risk for GDM, following the dominant genetic model (OR=1.7, 95 % CI 1.21-2.39, p=0.002), the recessive genetic model (OR=2.05, 95 % CI 1.04-4.03, p=0.03), and the additive genetic model (OR=1.62, 95 % CI 1.13-2.3, p=0.008). This association persisted after adjusting for age, T1DM, T2DM, and polycystic ovary syndrome (PCOS). Carrying BDNF rs925946 polymorphism predisposes to a higher risk of GDM pathogenesis. Its role and implications warrant further investigation, especially when considering preventive measures for GDM development.

The relationship between the rs6265 polymorphism of the BDNF gene and the level of serum neurotrophic factor in patients with Parkinson's disease

To evaluate the clinical features and the level of serum brain-derived neurotrophic factor (BDNF) in groups of patients with Parkinson's disease (PD) differentiated by the genotypes of BDNF polymorphism (rs6265). The level of serum BDNF in the biomarkers' multiplex panel of neurodegenerative diseases (HNDG3MAG-36K) was assessed in 134 PD patients. Allele discrimination was carried out by real-time PCR using TaqMan probes for the analysis of BDNF rs6265 polymorphism in groups of patients and controls (n=192) matched for sex, age and ethnicity. Comparing the distribution of rs6265 genotypes and alleles between groups of patients and controls no significant differences were found (p>0.05). Serum BDNF levels varied significantly by genotype (rs6265) among PD patients. Minimum mean serum BDNF level (320.1±164.6 pg/ml) was noted for individuals with the AA genotype, which significantly differs from the corresponding indicator among individuals with GA (2944.2±1590.6 pg/ml; p=0.0001) and GG genotypes (2949.4±1620.6 pg/ml; p=3.9×10-5). The concentration of BDNF significantly differed between patients with different forms of PD (p=0.0007) and increased as the stage of the disease progressed according to Hoehn and Yahr staging scale (p=1.0×10-6). The BDNF rs6265 polymorphism was not associated with the development of PD in the studied population. The variability of the mean serum BDNF level was established depending on the genotype of the BDNF polymorphism in PD patients and a number of clinical features.

Day‐to‐day Sleep Variability in Val66Met BDNF Carriers: A Potential Biological Pathway Between BDNF Activity and Alzheimer’s Disease Pathology?

AbstractBackgroundWe previously showed that day‐to‐day sleep variability was associated with biomarkers of Alzheimer’s disease (AD) pathology. Given that brain‐derived neurotrophic factor (BDNF) activity has been involved in both AD and cognitive impacts of lifestyle risk factors, we sought to evaluate day‐to‐day sleep variability in those carrying the Met allele of the Val66Met BDNF polymorphism, which affects BDNF release. Additionally, we explored whether BDNF polymorphism modified the association between CSF AD pathology and day‐to‐day sleep variability.MethodThe PREVENT‐AD cohort enrolls dementia‐free persons with a parental history of sporadic AD. We characterized 203 dementia‐free participants from this cohort at the polymorphic BDNF locus, identifying 136 persons with genotype Val/Val (age 68.2±5.3y, 75%women), 67 Met heterozygotes/homozygotes (68.4±5.6y, 73% women, including six Met/Met homozygotes). After a week of actigraphy, we calculated these participants’ standard deviation of day‐to‐day sleep characteristics. We used t‐tests to compare day‐to‐day sleep variability in sleep characteristics between Val homozygotes and Met carriers. In a subsample of 101 participants, we assayed CSF Aβ42, t‐tau and p‐tau181, and used age‐ and sex‐adjusted linear regressions with an interaction term to test for moderation by BDNF genotype (36 Met carriers vs. 65 Val homozygotes) between sleep variability and CSF biomarker results.ResultAs compared to Val homozygotes, sleep was disturbed and unstable in BDNF Met carriers (heterozygotes/homozygotes). They had higher day‐to‐day variability in sleep fragmentation (activity counts, wake after sleep onset, fragmentation index), sleep onset latency, and sleep duration, resulting in weekly sleep patterns that were more fragmented and less efficient. Further, BDNF genotype moderated the association between CSF t‐tau and p‐tau181 with day‐to‐day sleep duration variability, such that only Met carriers showed an association between elevated tau concentration and sleep duration variability.ConclusionBDNF Met carriers had disturbed and unstable daily sleep patterns. Because the Met allele is known to decrease plasticity of neural mechanisms, the ability to achieve healthy and stable sleep may depend on such mechanisms. Thus, poorer sleep in Met carriers might be a biological mechanism by which altered BDNF activity affects tau pathology or, alternatively, accumulated AD pathology in Met carriers may disrupt sleep‐wake patterns.

Brain-Heart Axis: Brain-Derived Neurotrophic Factor and Cardiovascular Disease-A Review of Systematic Reviews.

The brain-heart axis is an intra- and bidirectional complex that links central nervous system dysfunction and cardiac dysfunction. In recent decades, brain-derived neurotrophic factor (BDNF) has emerged as a strategic molecule involved in both brain and cardiovascular disease (CVD). This systematic review of systematic reviews aimed to (1) identify and summarize the evidence for the BDNF genotype and BDNF concentration in CVD risk assessment, (2) evaluate the evidence for the use of BDNF as a biomarker of CVD recovery, and (3) evaluate rehabilitation approaches that can restore BDNF concentration. A comprehensive search strategy was developed using PRISMA. The risk of bias was assessed via ROBIS. Seven studies were identified, most of which aimed to evaluate the role of BDNF in stroke patients. Only two systematic reviews examined the association of BDNF concentration and polymorphism in CVDs other than stroke. The overall evidence showed that BDNF plays a fundamental role in assessing the risk of CVD occurrence, because lower BDNF concentrations and rs6265 polymorphism are often associated with CVD. Nevertheless, much work remains to be carried out in current research to investigate how BDNF is modulated in different cardiovascular diseases and in different populations.

Association of BDNF risk variant and dorsolateral cortical thickness with long-term treatment response to valproate in type I bipolar disorder: An exploratory study.

Valproate is among the most prescribed drugs for bipolar disorder; however, 87% of patients do not report full long-term treatment response (LTTR) to this medication. One of valproate's suggested mechanisms of action involves the brain-derived neurotrophic factor (BDNF), expressed in the brain areas regulating emotions, such as the prefrontal cortex. Nonetheless, data about the role of BDNF in LTTR and its implications in the structure of the dorsolateral prefrontal cortex (dlPFC) is scarce. We explore the association of BDNF variants and dorsolateral cortical thickness (CT) with LTTR to valproate in bipolar disorder type I (BDI). Twenty-eight BDI patients were genotyped for BDNF polymorphisms rs1519480, rs6265, and rs7124442, and T1-weighted 3D brain scans were acquired. LTTR to valproate was evaluated with Alda's scale. A logistic regression analysis was conducted to evaluate LTTR according to BDNF genotypes and CT. We evaluated CT differences by genotypes with analysis of covariance. LTTR was associated with BDNF rs1519480 and right dlPFC thickness. Insufficient responders with the CC genotype had thicker right dlPFC than TC and TT genotypes. Full responders reported thicker right dlPFC in TC and TT genotypes. In conclusion, different patterns of CT related to BDNF genotypes were identified, suggesting a potential biomarker of LTTR to valproate in our population.

Brain-Derived Neurotrophic Factor (BDNF) as a Predictor of Treatment Response in Major Depressive Disorder (MDD): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) has been studied as a biomarker of major depressive disorder (MDD). Besides diagnostic biomarkers, clinically useful biomarkers can inform response to treatment. We aimed to review all studies that sought to relate BDNF baseline levels, or BDNF polymorphisms, with response to treatment in MDD. In order to achieve this, we performed a systematic review of studies that explored the relation of BDNF with both pharmacological and non-pharmacological treatment. Finally, we reviewed the evidence that relates peripheral levels of BDNF and BDNF polymorphisms with the development and management of treatment-resistant depression.

Thirty years of BDNF study in central myelination: From biology to therapy.

Being the highest expressed neurotrophin in the mammalian brain, the brain-derived neurotrophic factor (BDNF) is essential to neural development and plasticity in both health and diseases. Following the discovery of BDNF by Yves-Alain Barde in 1982, the main feature of BDNF's activity in myelination was first described by Cellerino et al. in 1997. Since then, genetic manipulation of the BDNF-encoding gene and its receptors in murine models has revealed the contribution of BDNF to the myelinating process in the central nervous system (CNS). The series of BDNF or receptor mouse mutants as well as the BDNF polymorphism in humans have provided new insights into the roles that BDNF signaling plays in myelination in a complex manner. 2024 marks the 30th year of BDNF's research in myelination. Here, we share our perspective on the 30-year history of BDNF in the field of CNS myelination from phenotyping to therapeutic development, focusing on genetic evidence regarding the mechanism by which BDNF regulates myelin formation and repair in the CNS. This review also discusses the current hypotheses of BDNF's action on CNS myelination: axonal- and oligodendroglial-driven mechanisms, which may be ultimately activity-dependent. Last, this review raises the challenges and opportunities of developing BDNF-based therapies for neurodegenerative diseases, opening unanswered questions for future investigation.

Association of the Brain-Derived Neurotrophic Factor Gene (BDNF) Val66Met Polymorphism with Individual Alpha Peak Frequency and Alpha Power in Adults

—A single nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene (Val66Met) functions to regulate activity-dependent secretion of (BDNF), which plays an important role in neuroprotection and synaptic plasticity. In several studies, the Met allele was associated with lower electroencephalogram (EEG) α-power values, calculated in the standard frequency range, in young subjects. In addition to α-power, one of the inherited EEG correlates of brain functioning is individual alpha peak frequency (IAPF). Although IAPF has a separate functional role, its association with BDNF Val66Met polymorphism has not been studied. IAPF is also used to determine the boundaries of individual frequency ranges, which, unlike the standard ones, are more consistent with functional rhythm characteristics. Using a sample of 192 subjects aged 18–78 years, the association between parietal-occipital IAPF and BDNF polymorphism, as well as the genotype differences in α-power calculated in standard (8–12 Hz) and individual frequency ranges (from (IAPF –2) to (IAPF +2) Hz) were examined. A decrease of IAPF in Val/Met compared to Val/Val was observed. For power calculated in the individual frequency range, genetic differences in both eyes-closed (Val/Met > homozygous genotypes) and eyes-open (Val-carriers > Met/Met) conditions were revealed. Analysis within the standard frequency range showed differences only in the eyes-open condition, which could be due to a shift of power indicators calculated in the α-rhythm functional range to the low frequency region among Val/Met carriers, which showed a decrease in IAPF. The results suggest that the inclusion of Val/Met in the pooled group of Met carriers in the analysis of genetic differences in brain activity may level out the differences between the Val/Val and Val/Met genotypes and show the advantage of using individual frequency bands in the analysis of BDNF Val66Met-associated EEG features.

Val66Met Polymorphism of Brain-Derived Neurotrophic Factor (BDNF) is Associated with Individual Alpha Peak Frequency and Alpha Power in Adults

Single-nucleotide polymorphism within the BDNF gene (Val66Met) influences activity-dependent secretion of the brain-derived neurotrophic factor (BDNF), which affects neuroprotection and synaptic plasticity. Several studies found associations between Met allele and lower power of the EEG α-rhythm determined in the standard frequency range in young adults. Along with the power, one of the highly heritable EEG correlates of brain functions is the individual α-peak frequency (IAPF). Although IAPF has independent functional significance, its association with the Val66Met BDNF polymorphism has not been studied. IAPF is also used to determine the boundaries of individual frequency ranges; in contrast to the standard ones, they reflect functional characteristics of rhythms to a greater extent. We explored in 192 subjects aged 18–78 years whether parieto-occipital IAPF is associated with BDNF polymorphism and tested genotypic differences in α-power calculated in standard (8−12 Hz) and individual (from (IAPF –2) to (IAPF +2) Hz) frequency ranges. IAPF was decreased in Val/Met in comparison to Val/Val. For individual frequency range, genetic differences were found in both eyes closed (Val/Met homozygous genotypes) and eyes open (Val-carriers Met/Met) condition. For standard frequency range – only in eyes open condition, which may be due to a shift of the α-functional range towards a region of low frequencies among Val/Met-carriers that showed a decrease in IAPF. The results indicate that the inclusion of Val/Met in the combined group of Met-carriers in the analysis of genetic differences in brain activity can eliminate the differences between Val/Val and Val/Met genotypes, as well as the advantage of using individual frequency bands in the analysis of BDNF-associated features of EEG.

Brain‐derived neurotrophic factor genes are associated with neuropsychiatric symptom progression in dementia. The Cache county dementia progression study

AbstractBackgroundPolymorphisms in genes coding for the neurotrophin, brain‐derived neurotrophic factor (BDNF) or its receptors, have been associated with Alzheimer’s disease and related disorders (ADRD), with sex‐dependent effects. Associations with neuropsychiatric symptom (NPS) progression after dementia onset has been largely unexplored. In a population‐based cohort, we examined the relationships between BDNF gene single‐nucleotide polymorphisms (SNPs) and NPS progression after dementia onset.Method880 participants [61.3% female; mean (SD) age = 82.0 (71) years] with dementia [68.2% AD; 13.5% Vascular Dementia (VaD); 18.3% other dementia (OD)] were assessed on the Neuropsychiatric Inventory (NPI) every six‐to‐18 months. Mean(SD) baseline dementia duration was 2.9(2.7) years. The following SNPs were examined as predictors of NPI scores over time in linear mixed‐effects models: rs6265 (BDNF G196A/Val66Met), rs56164415 (BDNF C270T), rs2289656 (NTRK2 receptor TrkB), and rs2072446 (NGFR p75NTR). Covariates included age of dementia onset, education, apolipoprotein E genotype, and dementia type and duration at baseline.ResultSex‐dependent effects were found for two SNPs. Compared to those with major alleles, males with the rs56164415 minor allele exhibited a lower initial Apathy score, that increased over time (C/t*sex*time2:b = ‐0.063, SE = 0.029, p = .033); by contrast, females showed no differences by SNP alleles. Females homozygous for the rs2289656 minor allele exhibited a rapid increase in Anxiety that decreased over time (t/t*sex*time2: b = ‐0.145, SE = 0.054, p = .0073). For both sexes, presence of minor alleles for BDNF polymorphisms rs6265 (G/a*time2: b = ‐0.017, SE = 0.004, p < .001; a/a*time2: b = ‐0.035, SE = 0.013, p = .006) and rs56164415 (C/t*time2: b = 0.019, SE = 0.005, p < .001) was associated with increased NPI Agitation/Aggression well after baseline. Rs6265 minor allele homozygotes (a/a*time2: b = ‐0.049, SE = 0.013, p < .001) and rs2072446 minor allele carriers (Ct/tt*time2: b = ‐0.012, SE = 0.005, p = .025) exhibited initial increases in Delusions, which diminished approximately 5 years thereafter.ConclusionSpecific BDNF genotypes were associated with NPS presentation after dementia onset, with some sex‐dependent effects. Future research on enhancing BDNF signaling may present possible targets for intervention.

Association between chronic tinnitus and brain-derived neurotrophic factor antisense RNA polymorphisms linked to the Val66Met polymorphism in BDNF

Tinnitus is the sound heard in the ear or head of a person in the absence of external stimuli. Its etiopathogenesis is still not fully understood and the etiological causes responsible for tinnitus are quite variable. Brain-derived neurotrophic factor (BDNF) is one of the key neurotrophic factors in the growth, differentiation, and survival of neurons and in the developing auditory pathway, including the inner ear sensory epithelium. The regulation of BDNF gene is known to be managed by BDNF antisense (BDNF-AS) gene. BDNF-AS is located downstream of the BDNF gene and transcribes a long non-coding RNA. Inhibition of BDNF-AS upregulates BDNF mRNA, which increases protein levels and stimulates neuronal development and differentiation. Thus, BDNF and BDNF-AS both may play roles in the auditory pathway. Polymorphisms in both genes may have impact on hearing performance. A link was suggested between tinnitus and BDNF Val66Met polymorphism. However, there is no study questioning the relationship of tinnitus with BDNF-AS polymorphisms linked with BDNF Val66Met polymorphism. Therefore, this study aimed to scrutinize the role of BDNF-AS polymorphisms showing linkage with the BDNF Val66Met polymorphism in the course of tinnitus pathophysiology. Six BDNF-AS polymorphisms were analyzed on the tinnitus patients (n = 85) and the control subjects (n = 60) by Fluidigm Real-Time PCR using the Fluidigm Biomark microfluidic platform. When BDNF-AS polymorphisms were compared between the groups in terms of genotype and gender distribution, statistically significant differences were detected in rs925946, rs1519480, and rs10767658, polymorphisms (p less than 0.05). When the polymorphisms were compared by the duration of tinnitus, significant differences were found in rs925946, rs1488830, rs1519480, and rs10767658 polymorphisms (p less than 0.05). According to genetic inheritance model analysis, 2.33 and 1.53-fold risks were found for the rs10767658 polymorphism in the recessive and the additive models, respectively. For the rs1519480 polymorphism, a 2.25 fold risk was observed in the additive model. For the rs925946 polymorphism, 2.44 fold protective effect in dominant model, and 0.62 fold risk was found in the additive model. In conclusion, four of the polymorphisms in BDNF-AS gene (rs955946, rs1488830, rs1519480, and rs10767658) are potential gene loci that may play a role in the auditory pathway and affect auditory performance.

BDNF and stress/mood-related interactions on emotional disorder symptoms, executive functioning, and deliberate self-harm

Some prior research has suggested that the brain-derived neurotrophic factor (BDNF) gene may amplify responses related to life stress (e.g., depression and anxiety) or associated with negative moods (e.g., self-harm and diminished cognitive functioning). The purpose of this study was to investigate whether stress/mood-related associations with depressive and anxiety symptoms, deliberate self-harm, and executive functioning (EF) are moderated by genotypic variations in BDNF rs10835210 (a relatively understudied BDNF polymorphism) in a nonclinical sample. As part of a larger study, European American social drinkers (N = 132; 43.9% female; M age = 26.0, SD = 7.6) were genotyped for BDNF rs10835210 and were administered self-report measures of subjective life stress, depressive and anxiety symptoms, and history of non-suicidal self-injury (NSSI) and behavioral measures of EF and deliberate self-harm. Results indicated that BDNF significantly moderated the life stress associations with depressive symptoms and NSSI, the anxious mood association with EF, and the depressed mood association with deliberate self-harm behavior. Each of these BDNF × stress/mood interactions were characterized by stress/mood associations that were stronger in individuals with the AA genotype (homozygous for the minor allele) than in individuals possessing a genotype that included the major allele (AC or CC). The main limitations of the present study were use of a cross-sectional design, modest sample size, and investigating only one BDNF polymorphism. Despite these limitations and though preliminary, current findings suggest that variations in BDNF may confer vulnerability to stress or mood, which may result in more adverse emotional, cognitive, or behavioral outcomes.

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.

286. Genetic Polymorphism of Brain-Derived Neurotrophic Factor is Related to Antidepressant Efficacy and Treatment-Induced Hippocampal Plasticity in Patients With Major Depressive Disorder: CAN-BIND-1 Study

286. Genetic Polymorphism of Brain-Derived Neurotrophic Factor is Related to Antidepressant Efficacy and Treatment-Induced Hippocampal Plasticity in Patients With Major Depressive Disorder: CAN-BIND-1 Study

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.

Brain-Derived Neurotrophic Factor Val66Met Genotype Modulates Latent Inhibition: Relevance for Schizophrenia.

Latent inhibition (LI) is a measure of selective attention and learning relevant to Schizophrenia (SZ), with 2 abnormality poles: Disrupted LI in acute SZ, thought to underlie positive symptoms, and persistent LI (PLI) in schizotypy and chronic SZ under conditions where normal participants fail to show LI. We hypothesized that Brain-Derived Neurotrophic Factor (BDNF)-Met genotype shifts LI toward the PLI pole. We investigated the role of BDNF-Val66Met polymorphism and neural activation in regions involved in LI in mice, and the interaction between the BDNF and CHL1, a gene associated with SZ. No LI differences occurred between BDNF-wild-type (WT) (Val/Val) and knock-in (KI) (Met/Met) mice after weak conditioning. Chronic stress or stronger conditioning disrupted LI in WT but not KI mice. Behavior correlated with activation in infralimbic and orbitofrontal cortices, and nucleus accumbens. Examination of LI in CHL1-KO mice revealed no LI with no Met alleles (BDNF-WTs), PLI in CHL1-WT mice with 1 Met allele (BDNF-HETs), and PLI in both CHL1-WTs and CHL1-KOs with 2 Met alleles (BDNF-KIs), suggesting a shift to LI persistence with the number of BDNF-Met alleles in the CHL1 model of acute SZ. Results support a role for BDNF polymorphisms in gene-gene and gene-environment interactions relevant to SZ. BDNF-Met allele may reduce expression of some acute SZ symptoms, and may increase expression of negative symptoms in individuals with chronic SZ. Evaluation of (screening for) SZ phenotypes associated with mutations at a particular locus (eg, CHL1), may be masked by strong effects at different loci (eg, BDNF).

Gene- and Gender-Related Decrease in Serum BDNF Levels in Alzheimer’s Disease

Brain-derived neurotrophic factor (BDNF) has a protective role in Alzheimer's disease (AD). Oxidative stress and inflammatory cytokines are potentially implicated in AD risk. In this study, BDNF was detected in serum of AD and mild cognitive impairment (MCI) patients and investigated in association with gene polymorphisms of BDNF (Val66Met and C270T), of some oxidative stress-related genes (FOXO3A, SIRT3, GLO1, and SOD2), and of interleukin-1 family genes (IL-1α, IL-1β, and IL-38). The APOE status and mini-mental state examination (MMSE) score were also evaluated. Serum BDNF was significantly lower in AD (p = 0.029), especially when comparing the female subsets (p = 0.005). Patients with BDNFVal/Val homozygous also had significantly lower circulating BDNF compared with controls (p = 0.010). Moreover, lower BDNF was associated with the presence of the T mutant allele of IL-1α(rs1800587) in AD (p = 0.040). These results were even more significant in the female subsets (BDNFVal/Val, p = 0.001; IL-1α, p = 0.013; males: ns). In conclusion, reduced serum levels of BDNF were found in AD; polymorphisms of the IL-1α and BDNF genes appear to be involved in changes in serum BDNF, particularly in female patients, while no effects of other gene variants affecting oxidative stress have been found. These findings add another step in identifying gender-related susceptibility to AD.

Risk and Protective Factors for Childhood Physical Abuse and Suicidal Ideation: The Effect of Brain-Derived Neurotrophic Factor Polymorphism and Social Support.

This study aimed to explore the relationship between childhood physical abuse and suicidal ideation considering the effects of genetic and environmental factors in patients with post-traumatic stress disorder (PTSD) by focusing on brain-derived neurotrophic factor (BDNF) polymorphism and social support, respectively. One-hundred fourteen patients with PTSD and 94 healthy controls (HCs) were genotyped with respect to BDNF Val66Met polymorphism. All participants underwent psychological assessments. The hierarchical regression analysis and the simple slope analysis were conducted. As for patients with PTSD, the moderation effect of BDNF polymorphism was significant but not for social support. Specifically, the BDNF Val/Val genotype worked as a risk factor and strengthens the relationship between childhood physical abuse and suicidal ideation. As for the HCs, the significant moderation effect was found only in social support, but not for BDNF polymorphism. The relationship between childhood physical abuse and suicidal ideation was weakened for the HCs with high social support. This study demonstrated a significant BDNF genetic vulnerability for suicide in patients with PTSD who experienced childhood physical abuse. Our results suggested that social support provided a mitigating effect on the relationship between childhood physical abuse and suicidal ideation only in the HCs.

APOE & BDNF polymorphisms interact to affect memory performance at baseline in adolescent athletes

ABSTRACT Although several single-nucleotide polymorphisms have been associated with cognitive functioning in a variety of healthy and clinical samples, the influence of gene × gene interactions on cognition is poorly understood. The purpose of this study was to examine interactive relationships between apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) polymorphisms on cognitive functioning in a sample of healthy adolescent athletes. Participants of this cross-sectional study included 78 student-athletes (52.6% male; age: M = 13.31, SD = 1.23). Athletes completed the Immediate Post-Concussion and Cognitive Testing (ImPACT) computerized battery at baseline. APOE and BDNF genotypes were determined with buccal samples (APOE ε4+: n = 26; APOE ε4-: n = 52; BDNF Met+: n = 23; BDNF Met-: n = 55). Two-way analyses of variance (ANOVAs) were used to evaluate the associations among APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) genotypes and the ImPACT cognitive composites and two-factor model. No main effects were observed for either APOE or BDNF genotypes across the cognitive outcomes. However, there was a significant APOE × BDNF genotype interaction for the verbal (p=.009, η p 2 =.091) and visual (p = .012, η p 2 =.082) memory composites and the memory factor (p = .001, η p 2 =.133), such that ε4+/Met+ carriers demonstrated poorer performance relative to other allele combinations. No significant interactions were observed for the visual motor speed (p = .263, η p 2 =.017) or reaction time (p = .825, η p 2 =.001) composites or the speed factor (p = .205, η p 2 =.022). Our findings suggest an important relationship between APOE and BDNF genotypes on verbal and visual memory performance in healthy adolescent athletes. Clinicians may use this information to offer individualized concussion management based on individual athlete characteristics related to genetics and cognition.

Memory Modulation by Exercise in Young Adults Is Related to Lactate and Not Affected by Sex or BDNF Polymorphism.

Simple SummaryThe health and cognitive benefits associated with physical exercise are widely acknowledged. However, exercise characteristics responsible for the improvement in cognition, along with the underlying mechanisms, remain to be elucidated. In an attempt to resolve these questions, our study compares cognitive outcomes after two distinct exercise modes in young adults. Specifically, we have examined the differences between high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MIE) on visuospatial and declarative memory, contemplating the influence of exercise-associated parameters such as released lactate and non-modifiable factors, including BDNF polymorphism and biological sex. Our results demonstrate the relevance of exercise intensity and intensity-dependent lactate release in modulating cognitive improvement following exercise with no association with the non-modifiable factors mentioned above. These data suggest that the exercise characteristics and intensity of exercise sessions should be carefully considered to optimize cognitive response in young adults. Conversely, the consideration of genotype and biological sex is inappreciable.Currently, high-intensity interval exercise (HIIE) is on the rise compared to moderate-intensity exercise (MIE) due to its similar benefits for health and performance with low time requirements. Recent studies show how physical exercise can also influence cognitive function, although the optimal dose and underlying mechanisms remain unknown. Therefore, in our study, we have compared the effects on visuospatial and declarative memory of different exercise intensities (HIIE vs. MIE), including possible implicated factors such as lactate released after each session and the Brain-Derived Neurotrophic Factor (BDNF) genotype. Thirty-six undergraduate students participated in this study. The HIIE session consisted of a 3 min warm-up, four 2 min sets at 90–95% of the maximal aerobic speed (MAS) with 2 min of passive recovery between sets, and a 3 min cooldown, and the MIE session implies the same total duration of continuous exercise at 60% of the MAS. Better improvements were found after HIIE than MIE on the backward condition of the visuospatial memory test (p = 0.014, ηp2 = 0.17) and the 48 h retention of the declarative memory test (p = 0.04; d = 0.34). No differences were observed in the forward condition of the visuospatial memory test and the 7-day retention of the declarative memory test (p > 0.05). Moreover, non-modifiable parameters such as biological sex and BDNF polymorphism (Val/Val, Val/Met, or Met/Met) did not modulate the cognitive response to exercise. Curiously, the correlational analysis showed associations (p < 0.05) between changes in memory (visuospatial and declarative) and lactate release. In this sense, our results suggest an important role for intensity in improving cognitive function with exercise, regardless of genetic factors such as biological sex or BDNF Val66Met polymorphism.