BDNF Val66Met Research Articles

Dopamine in Sports: A Narrative Review on the Genetic and Epigenetic Factors Shaping Personality and Athletic Performance.

This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene-environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies.

Associations between methamphetamine use disorder and SLC18A1, SLC18A2, BDNF, and FAAH gene sequence variants and expression levels.

Assessing candidate gene sequence variations and expression helps to understand methamphetamine use disorder and inform potential treatments. We investigated single nucleotide polymorphisms (SNPs) and gene expression in four candidate genes: SLC18A1, SLC18A2, BDNF, and FAAH, between controls and people with methamphetamine use disorder. Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. SLC18A1, SLC18A2, BDNF, and FAAH SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR. SLC18A1 Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; p = .007). SLC18A2 variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity (p = .003) and positively associated with inhibitory control performance (p = .006), respectively. BDNF Val66Met was associated with the severity of use (p = .008). SLC18A2 and FAAH mRNA levels were lower in people who use methamphetamine relative to controls (p = .021 and .010, respectively). SLC18A1 is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood SLC18A2 and FAAH mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release, and higher anandamide levels in this clinical group, which may be potential therapeutic targets.

An Observational Case-control Study for BDNF Val66Met Polymorphism and Serum BDNF in Patients with Major Depressive Disorder (MDD)

An Observational Case-control Study for BDNF Val66Met Polymorphism and Serum BDNF in Patients with Major Depressive Disorder (MDD)

Correlation between human BDNF rs6265 gene polymorphism and type-2 diabetes and diabetic peripheral neuropathy

Background & objective: Diabetes mellitus is quite common and globally prevalent condition affecting patients’ quality of life. Patients who have type 2 diabetes mellitus (T2DM), are more likely to get diabetic peripheral neuropathy (DPN), which may affect feet, legs, hand, and arm. A BDNF gene rs6265 polymorphism in humans results in the substitution of valine with methionine at codon 66 (Val66Met). We aimed to find the possible link between human BDNF rs6265 gene polymorphism and T2DM with and without peripheral neuropathy and compare it with healthy subjects in Kirkuk City, Iraq. Methodology: One hundred subjects were chosen to participate in this research, aged from 35 to 75 y and divided into three groups: 35 DPN, 35 T2DM patients, and 30 healthy controls were selected randomly for BDNF gene rs6265 SNP screening by using conventional PCR with specific sets of primers. Products of PCR for patients and control groups were run on the gel electrophoresis to detect the SNP rs6265 fragment. A nerve-conducting study was used to examine DPN. Results: The observed results demonstrated the presence of two types of alleles identified as genotypic variants (GG and GA) among all participants in this investigation. By applying the Hardy-Weinberg Equilibrium principle (HWE) for both patient and control groups, the results proved that there was a statistically significant variance (P < 0.05) in the genotypic frequencies between each of the groups that had been studied. The wild homozygous GG genotype in type 2 diabetic without neuropathy, with DPN, and healthy control group were 51.4%, 40% and 80% respectively. The heterozygous GA genotype were 48.6%, 60% and 20%, respectively in the three groups. Conclusion: The present study showed that the BDNF (Val66Met) rs6265 polymorphism is associated with type 2 diabetes mellitus and diabetic peripheral neuropathy in heterozygous allele G/A (Met/Met) and homozygous allele GG (Val/Val) genotype. Also, the current study found the absence of the mutant genotype AA, possibly due to the evidence that the distribution of the BDNF polymorphisms varies widely among different ethnic groups. Abbreviations: BDNF - Brain-derived neurotrophic factor; DPN - Diabetic peripheral neuropathy Keywords: Type2 diabetes mellitus; Diabetic peripheral neuropathy; Brain-Derived Neurotrophic Factor; BDNF rs6265 SNP; BDNF Val66Met polymorphism. Citation: Hamid R, Al-Wasiti E, Jabbar AM. Correlation between human BDNF rs6265 gene polymorphism and type-2 diabetes and diabetic peripheral neuropathy. Anaesth. pain intensive care 2024;28(4):752−756. DOI: 10.35975/apic.v28i4.2517 Received: March 08, 2024; Reviewed: April 20, 2024; Accepted: April 28, 2024

Comparison of Val66met Polymorphism of BDNF gene in patients of bipolar disorder and healthy controls.

IntroductionThe study aims to explore the utility of BDNF Val66Met polymorphism as a potential biomarker in Indian bipolar disorder patients and its correlation with clinical characteristics.ObjectivesGenotyping Val66Met in BDNF geneExploring its association with bipolar disorder (BD).Methods150 consenting BD patients and matched controls were recruited using a case-control study design. BD severity was assessed using Young’s mania rating scale and the Clinical Global Impression - Severity (CGI-S) scale. BDNF Val66Met polymorphism was identified through real-time PCR after DNA extraction. Data was tested for normal distribution. Genotype frequencies between two groups were compared and the Hardy-Weinberg equilibrium assumptions were tested using Chi-Square tests. Clinical-genotypic associations were explored using the Kruskal-Wallis test and confirmed using hierarchical regression.ResultsOur sample had more males (60%) than females (40%) with mean age of 35.05 years. Most patients had established bipolar disorder and were severely ill (CGI: 38.75, YMRS). Val66Met SNP genotype frequency differed significantly between cases and controls. Val66Val genotype and Val allele were higher in cases. Results consistent with Hardy-Weinberg equilibrium.Table 1.Genotype frequencies of BDNF (rs6265) in cases and controlsGENOTYPECCCTTTCASES94(62.6%)47(31.3%)9(6%)CONTROL71(47.3%)69(46%)10(6.6%)CHI-SQUARE- 7.431DF(Degree of freedom) - 2p-value- 0.024Table 2.Dominant genotype frequencies in cases and controlsDOMINANT GENOTYPECCCT+TTCASES94(62.6%)56(37.3%)CONTROLS71(47.3%)79(52.6)CHI-SQUARE-7.125DF(Degree of freedom)-1p-value-0.007Table 3.Allelic frequencies of BDNF (rs6265) in BD cases and healthy controlsALLELIC VARIATIONCTCASES235(78.3%)65(21.6%)CONTROLS211(70.3%)89(29.6%)CHI-SQUARE-5.032DF(Degree of freedom)-1p-value- 0.024ConclusionsOur study found that Val66Val genotype and Val allele were higher in cases and could be a potential biomarker for bipolar disorder (BD), which is consistent with previous research conducted on the European population. However, further investigations are required to gain a more comprehensive understanding of its impact on BD, including its association with serum BDNF levels, treatment outcomes, and a more diverse study population.Disclosure of InterestNone Declared

BDNF Val66Met polymorphism moderates negative symptom expression of bully victimization through resilience in Taiwanese youth

ABSTRACT Bully victimization is known to cause adverse psychological outcomes; however, resilience may mitigate the more adverse effects. Little is known regarding the role played by BDNF Val66Met polymorphism in youth resilience against psychological harm caused by bully victimization. In this cross-sectional study, a community sample of 598 participants (M age = 20.1 ± 1.4 years, 48.8% males) completed the questionnaire on bully victimization, resilience, and psychological symptoms. Salivary genomic DNA was genotyped for the BDNF Val66Met polymorphism. A path analysis was used to test the mediating role of resilience in the association between bully victimization and psychological symptoms. Furthermore, the BDNF genotype was added to the model to explore its moderating effects on the mediating role of resilience in the path with 5000 bootstrapped samplings using SPSS PROCESS Macro. Results revealed a significant indirect effect via resilience that accounted for 17.2% of the association between bully victimization and psychological symptoms. While the Val66Met polymorphism interacted with bully victimization to predict resilience scores, bully victimization was more strongly associated with poor resilience (F = 4.59, p = 0.03) in subjects with the Met/Met genotype (β=-3.22, p < 0.001), as compared to participants with other genotypes (β=-1.33, p = 0.051). Findings suggest a gene-environment interaction effect on psychological resilience in bully-victimized youth.

Transcranial direct current stimulation and neuronal functional connectivity in MCI: role of individual factors associated to AD.

Alzheimer's disease (AD) encompasses a spectrum that may progress from mild cognitive impairment (MCI) to full dementia, characterized by amyloid-beta and tau accumulation. Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic option, but its efficacy in relation to individual genetic and biological risk factors remains underexplored. To evaluate the effects of a two-week anodal tDCS regimen on the left dorsolateral prefrontal cortex, focusing on functional connectivity changes in neural networks in MCI patients resulting from various possible underlying disorders, considering individual factors associated to AD such as amyloid-beta deposition, APOE ϵ4 allele, BDNF Val66Met polymorphism, and sex. In a single-arm prospective study, 63 patients with MCI, including both amyloid-PET positive and negative cases, received 10 sessions of tDCS. We assessed intra- and inter-network functional connectivity (FC) using fMRI and analyzed interactions between tDCS effects and individual factors associated to AD. tDCS significantly enhanced intra-network FC within the Salience Network (SN) and inter-network FC between the Central Executive Network and SN, predominantly in APOE ϵ4 carriers. We also observed significant sex*tDCS interactions that benefited inter-network FC among females. Furthermore, the effects of multiple modifiers, particularly the interaction of the BDNF Val66Met polymorphism and sex, were evident, as demonstrated by increased intra-network FC of the SN in female Met non-carriers. Lastly, the effects of tDCS on FC did not differ between the group of 26 MCI patients with cerebral amyloid-beta deposition detected by flutemetamol PET and the group of 37 MCI patients without cerebral amyloid-beta deposition. The study highlights the importance of precision medicine in tDCS applications for MCI, suggesting that individual genetic and biological profiles significantly influence therapeutic outcomes. Tailoring interventions based on these profiles may optimize treatment efficacy in early stages of AD.

Baseline serum brain-derived neurotrophic factor association with future cognition in community-dwelling older adults undergoing annual memory screening

ABSTRACT Objectives It has been shown that peripheral measures of brain-derived neurotrophic factor (BNDF), an important neurotrophin instrumental to the biology of learning, may contribute to predicting cognitive decline. However, the two primary forms of BDNF, mature (mBDNF) and pro (proBDNF), and how they contribute to cognition longitudinally has not been well studied. Methods Eighty-two older adults (average age 72.2 ± 6.4 years) provided blood samples at two time points separated on average by 4.2 years while participating in an annual memory screening that included the MoCA (Montreal Cognitive Assessment) and GDS (Geriatric Depression Scale). Both mBDNF and proBDNF from serum were quantified at each time point. Whole blood samples were genotyped for APOE and BDNF Val66Met. Results Using logistic regression analysis controlling for age, sex, baseline MoCA score, APOE, and BDNF, higher baseline mBDNF was associated with subjects whose screening score was near maximum or maximum (as defined by MoCA score of 29 or 30) at the second collection visit. APOE was a significant contributing factor; however, BDNF Val66Met was not. Using a similar logistic regression analysis, baseline proBDNF was not found to be associated with future cognition. Discussion This study further supports that mBDNF measured in the serum of older adults may reflect a protective role while proBDNF requires further investigation.

No Interaction Between BDNF Val66Met and APOE ε4 on PET‐Based Amyloid and Tau Measurements

AbstractBackgroundThe interaction between the BDNF Val66Met gene and APOE ε4 gene on Alzheimer’s disease (AD) pathology is not fully understood. We aimed to determine how this interaction impacts PET based amyloid and tau measurements, hippocampal volume, and auditory verbal learning tests (AVLT) performance in cognitively unimpaired (CU) older adults.MethodData from 216 participants were used in this analysis. For the whole data set, the mean age was 75.56 ± 7.52 years, mean education was 16.82 ± 2.40 years, and 55% of the participants were female (118 females and 98 male). Linear regression models that adjusted for age, sex, education, were used to quantify main effects and interactions between APOE ε4 carrier status and BDNF Val66Met carrier status. Outcome measures included AV‐45 SUVR, tau meta‐ROI, hippocampal volume, AVLT Delayed Recall, and AVLT Total Recall.ResultThere was a main effect on APOE ε4 carrier status on amyloid load (β = 0.11, 95% CI (0.04, 0.17), p = 0.001), but no main effect for BDNF on amyloid load (β = ‐0.003, 95% CI (‐0.06, 0.06) p = 0.91). The interaction between APOE ε4 carrier status and BDNF Met carrier status was not significant (β = 0.03, 95% CI (‐0.07, 0.13), p = 0.58). There was no main effect on APOE ε4 carrier status on tau load (β = 0.003, 95% CI (‐0.06, 0.06), p = 0.93). There was also no main effect on BDNF on tau load (β = ‐0.0006, 95% CI (‐0.05, 0.05), p = 0.98) and the interaction between APOE ε4 carrier status and BDNF Met carrier status was not significant (β = 0.03, 95% CI (‐0.06, 0.12), p = 0.49). There were no significant main effects or interactions on hippocampal volume and cognitive measures.ConclusionThis cross‐sectional study found no significant interaction between APOE ε4 carrier status and BDNF met carrier status on measures of amyloid and tau load as well as hippocampal volume and cognition. These findings cast doubt on the BDNF Met allele’s role in moderating AD‐related pathological changes.

A Novel Mutation in the MAP7D3 Gene in Two Siblings with Severe Intellectual Disability and Autistic Traits: Concurrent Assessment of BDNF Functional Polymorphism, X-Inactivation and Oxidative Stress to Explain Disease Severity.

Intellectual disabilities (ID) and autism spectrum disorders (ASD) are characterized by extreme genetic and phenotypic heterogeneity. However, understanding this heterogeneity is difficult due to the intricate interplay among multiple interconnected genes, epigenetic factors, oxidative stress, and environmental factors. Employing next-generation sequencing (NGS), we revealed the genetic cause of ID and autistic traits in two patients from a consanguineous family followed by segregation analysis. Furthermore, in silico prediction methods and 3D modeling were conducted to predict the effect of the variants. To establish genotype-phenotype correlation, X-chromosome inactivation using Methylation-specific PCR and oxidative stress markers were also investigated. By analyzing the NGS data of the two patients, we identified a novel frameshift mutation c.2174_2177del (p.Thr725MetfsTer2) in the MAP7D3 gene inherited from their mother along with the functional BDNF Val66Met polymorphism inherited from their father. The 3D modeling demonstrated that the p.Thr725MetfsTer2 variant led to the loss of the C-terminal tail of the MAP7D3 protein. This change could destabilize its structure and impact kinesin-1's binding to microtubules via an allosteric effect. Moreover, the analysis of oxidative stress biomarkers revealed an elevated oxidative stress in the two patients compared to the controls. To the best of our knowledge, this is the first report describing severe ID and autistic traits in familial cases with novel frameshift mutation c.2174_2177del in the MAP7D3 gene co-occurring with the functional polymorphism Val66M in the BDNF gene. Besides, our study underlines the importance of investigating combined genetic variations, X-chromosome inactivation (XCI) patterns, and oxidative stress markers for a better understanding of ID and autism etiology.

Background EEG Activity Mediates the Association between the BDNF Val66Met Polymorphism and Memory during Aging

Background EEG Activity Mediates the Association between the BDNF Val66Met Polymorphism and Memory during Aging

Brain-derived neurotrophic factor serum concentration and BDNF Val66Met polymorphism in patients with peripheral artery disease: the importance of heart failure

Brain-derived neurotrophic factor serum concentration and BDNF Val66Met polymorphism in patients with peripheral artery disease: the importance of heart failure

Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population.

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.

Impact of transcranial direct current stimulation on white matter microstructure integrity in mild cognitive impairment patients according to effect modifiers as risk factors for Alzheimer's disease.

Little research exists on how individual risk factors for Alzheimer's disease (AD) affect the intermediate phenotype after transcranial direct current stimulation (tDCS), despite the importance of precision medicine-based therapeutic approaches. To determine how an application of sequential tDCS (2 mA/day, left dorsolateral prefrontal cortex, 10 sessions) affects changes in white matter (WM) microstructure integrity in 63 mild cognitive impairment (MCI) patients with effect modifiers such as Aβ deposition, APOE ε4 carrier status, BDNF Val66Met polymorphism status, and sex. We examined individual effect modifier-by-tDCS interactions and multiple effect modifiers-by-tDCS interactions for diffusion metrics. We also evaluated the association between baseline Aβ deposition and changes in WM microstructure integrity following tDCS. We found that APOE ε4 carrier status and sex had a significant interaction with tDCS, resulting in increased fractional anisotropy (FA) in the right uncinate fasciculus (UF) after stimulation. Additionally, we observed multiple effect modifiers-by-tDCS interactions on WM integrity of the right UF, leading to a more pronounced increase in FA values in APOE ε4 carriers and females with Val66 homozygotes. Finally, baseline Aβ deposition was positively associated with a difference in FA of the left cingulum in the hippocampal area, which showed a positive association with the changes in the score for delayed memory. Our study shows the differential impact of individual AD risk factors on changes in the early intermediate phenotype after sequential tDCS in MCI patients. This research emphasizes the importance of precision medicine approaches in tDCS for the prodromal stages of AD.

The Waist-Hip Ratio is a Mediator Between Serum Levels of Brain-Derived Neurotrophic Factor and Its Val66Met Polymorphism in Adolescents.

To explore anthropometric, metabolic and dietary factors associated with and their interplays with the Val66Met polymorphism at brain-derived neurotrophic factor (BDNF) gene (Bdnf) on serum BDNF levels in adolescents. Serum BDNF levels were quantified using an enzyme-linked immunosorbent assay in 644 high school students (278 males/366 females). A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for Bdnf Val66Met genotyping followed by verification using DNA sequencing. Serum levels of metabolic characteristics were assayed by routine methods. The intake of macro and micronutrients was collected by a three-day food record. Serum BDNF levels were found to be significantly different in the subjects with different genotypes of Bdnf Val66Met (Val/Val homozygotes, 60.05 ± 28.07 ng/mL vs Val/Met heterozygotes, 56.37 ± 29.34 ng/mL vs Met/Met homozygotes, 51.32 ± 24.54 ng/mL, p = 0.022). Among the 36 tested variables, waist-hip ratio (WHR) (β = -0.163, p < 0.001), iodine intake (β = 0.132, p = 0.001), heart rate (β = 0.108, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (β = 0.098, p = 0.011) and dietary fiber intake (β = 0.082, p = 0.084) were the predictor of serum BDNF levels, while SBP (β = 0.097, p = 0.013) and WHR (β = 0.091, p = 0.021) were related with Bdnf Val66Met. Moreover, WHR was observed to play a partial mediating role in the relationship between Bdnf Val66Met and serum BDNF levels (95% CI [-1.161, -0.087]) and contribute 13.05% of its total effect on serum BDNF levels. There are interplays between WHR and Bdnf Val66Met on serum BDNF levels, which may be among the explanations for the previous heterogeneous reports and provide novel insights into the regulation of serum BDNF levels.

Associations between the Efficiency of Hemispheric Verbal Memory Processes and the BDNF Val66Met Polymorphism in Men and Women

Associations between the Efficiency of Hemispheric Verbal Memory Processes and the BDNF Val66Met Polymorphism in Men and Women

Interactions of BDNF Val66met and dietary indices in relation to metabolic markers among patient with type 2 diabetes mellitus: a cross-sectional study

BackgroundGene–diet interaction is related to the progression of diabetes and cardiovascular diseases biomarkers. We aimed to evaluate the interaction between diet quality indices and BDNF Val66Mat (rs6265) on cardiometabolic markers among diabetic patients.MethodsThis cross-sectional study was conducted on 634 patients with type 2 diabetes mellitus, which were randomly recruited from diabetic centers in Tehran. Dietary intakes were estimated by a previously validated semi-quantitative food frequency questionnaire comprising 147 items. All participants were categorized into three categories, based on healthy eating index (HEI), diet quality index (DQI), and phytochemical index (PI) scores. Polymerase chain reaction was used for genotyping the BDNF Val66Met. Interactions were tested using analysis of covariance in adjusted and crude models.ResultsOur result showed that higher DQI, HEI, and PI scores significantly decrease body mass index and waist circumference among individuals with Met/Met, Val/Met, and Val/Val genotypes (P interactions < 0.05). Moreover, the highest quartile of the DQI and PI, compared to the lowest, showed lower TG level among Met allele carriers compared to Val/Val homozygotes (P interaction = 0.004 and 0.01, respectively) and a faster reduction in IL-18 and TC level was seen among Met/Met, Val/Met who had higher HEI intake than those with Val/Val genotype.ConclusionsBDNF Val66Met polymorphism may interact with HEI, DQI, and PI. We have revealed that Met allele acts as a protective allele for diabetic patients and may have a beneficial influence on cardio-metabolic factors through regulating dietary intake.

The effect of brain-derived neurotrophic factor Val66Met polymorphism on adolescent activity and rest rhythms, circadian preferences and attentional performance

BackgroundVariations in circadian regulating mechanisms generate different individual preferences in respect of sleep and activity timing, which are known as chronotypes. In this sense, specifically during adolescence, there is a greater tendency for an eveningness chronotype. One factor that has been shown to have an impact on circadian rhythm patterns, as well as on some aspects of cognitive function, is the relatively common Val66Met (rs6265) polymorphism in the human brain-derived neurotrophic factor gene. ObjectiveThis study aimed to evaluate the effect of the BDNF Val66Met polymorphism on the performance of adolescents in attentional tests, circadian preferences and activity-rest rhythm. Methods85 healthy high school students completed the Morningness-Eveningness Questionnaire to assess their circadian preferences; were evaluated using the Psychological Battery for Attention Assessment; and were categorized as carriers and non-carriers of the rs6265 polymorphism using the TaqMan rt-PCR technique. A subsample of 42 students had their activity/rest rhythm recorded by actigraphy for nine days from which sleep parameters were estimated. ResultsCircadian preference did not affect attentional performance (p > 0.1), but the time that the students attended school had an impact on all types of attention with morning shift students scoring higher, regardless of chronotype (p < 0.05). The presence of the BDNF Val66Met polymorphism was associated only with alternate attention performance (p < 0.05). Regarding actigraphy evaluation, the carriers of the polymorphism demonstrated significantly higher total time in bed, total sleep time, social jetlag, and earlier sleep onset. ConclusionsThe results indicate some degree of adaptation in the students' attentional performance, according to their school schedules. The presence of BDNF polymorphism demonstrated a counterintuitive impact on attentional performance, comparing to previous findings. The findings reinforce the effect of genetic traits on sleep-wake rhythm parameters, when objectively evaluated.

Abstract 151: Genetic Factors And Outcomes After Stroke: A Preliminary Analysis Of The Strong Study

Introduction: Measures of genetic variation have provided insight into underlying biology and treatment approaches in a number of medical sciences. The STRONG (“The Stroke, sTress, RehabilitatiON, and Genetics Study”) Study evaluated genetic polymorphisms in relation to stroke recovery. Methods: The STRONG Study recruited patients with a new stroke from 28 U.S. stroke centers. Entry criteria included age ≥18 years and new ischemic stroke or intracerebral hemorrhage. Visit 1 was during acute admission; Visit 2, 90 days post-stroke; Visit 3, 6 mo post-stroke; and Visit 4, 12 mo post-stroke. Linear regression examined specific genotypes in relation to 2 primary outcomes (change in grip force from V1-V2 and global function (SIS-ADL) at V2) and 2 secondary outcomes (depression (PHQ-8) at V2 and cognitive function (t-MoCA) at V4). No correction for multiple comparisons is made below. Results: There were 763 patients enrolled from 2016-2020, with mean age 63.1±14.9 years, 41.1% female, median NIHSS score 4 [2-9]. Data were available in 510 patients at Visit 2 and 482 at Visit 4. The BDNF val66met polymorphism (rs6265) was related to poorer V4 MoCA score (p=0.01). Presence of ApoE4 was not related to any endpoint. For the dopamine polygene score, a relationship with lower score (reduced dopamine neurotransmission) and greater depression (higher V2 PHQ-8 score) was suggested (p=0.1). A polymorphism (rs1842681) associated with chronic mRS score in a prior GWAS study (Neurology. 2019;92:e1271) was related to STRONG Study d90 mRS score (p=0.05). Three polymorphisms (rs76221407, rs150862264, rs182008837) associated with 3-mo mRS score in a separate GWAS study (Circ Res. 2019;124:114) were not related to STRONG Study d90 mRS score (p=.71-.78). ConclusionS: The STRONG Study collected genotypes and detailed longitudinal behavioral data during the year following stroke. Data do not support several hypotheses. However, presence of the BDNF val66met polymorphism may be related to poorer cognitive outcome. Lower dopamine gene score showed a trend with greater depression, consistent with a prior publication. Current findings support a prior GWAS finding for chronic mRS score. Genetics studies provide insights into inter-subject differences in recovery after stroke.

Exploring the role of BDNF Val66Met polymorphism on the impact of physical activity in cognitive performance in a community sample

Exploring the role of BDNF Val66Met polymorphism on the impact of physical activity in cognitive performance in a community sample