BDNF Polymorphism Research Articles

Effect of Transcutaneous Spinal Direct Current Stimulation in Patients with Painful Polyneuropathy and Influence of Possible Predictors of Efficacy including BDNF Polymorphism: A Randomized, Sham-Controlled Crossover Study.

Introduction: The neuromodulating effects of transcutaneous-spinal Direct Current Stimulation (tsDCS) have been reported to block pain signaling. For patients with chronic pain, tsDCS could be a potential treatment option. To approach this, we studied the effect of anodal tsDCS on patients with neuropathic pain approaching an optimal paradigm including the investigation of different outcome predictors. Methods: In this randomized, double-blinded, sham-controlled crossover study we recruited twenty patients with neurophysiologically evaluated neuropathic pain due to polyneuropathy (PNP). Variables (VAS; pain and sleep quality) were reported daily, one week prior to, and one week after the stimulation/sham period. Anodal tsDCS (2.5 mA, 20 min) was given once daily for three days during one week. BDNF-polymorphism, pharmacological treatment, and body mass index (BMI) of all the patients were investigated. Results: Comparing the effects of sham and real stimulation at the group level, there was a tendency towards reduced pain, but no significant effects were found. However, for sleep quality a significant improvement was seen. At the individual level, 30 and 35% of the subjects had a clinically significant improvement of pain level and sleep quality, respectively, the first day after the stimulation. Both effects were reduced over the coming week and these changes were negatively correlated. The BDNF polymorphism Val66Met was carried by 35% of the patients and this group was found to have a lower general level of pain but there was no significant difference in the tsDCS response effect. Neither pharmacologic treatment or BMI influenced the treatment effect. Conclusions: Short-term and sparse anodal thoracic tsDCS reduces pain and improves sleep with large inter-individual differences. Roughly 30% will benefit in a clinically meaningful way. The BDNF genotype seems to influence the level of pain that PNP produces. Individualized and intensified tsDCS may be a treatment option for neuropathic pain due to PNP.

Paired corticomotoneuronal stimulation of the preactivated ankle dorsiflexor: an open-label study of magnetic and electrical painless protocols.

Paired corticomotoneuronal stimulation (or electrical PCMS: ePCMS) is the repetitive pairing of an electrical stimulus to a nerve with a transcranial magnetic stimulation of the primary motor cortex (TMS-of-M1) to noninvasively influence spinal plasticity. We compared ePCMS with the new painless PCMS protocol pairing a magnetic stimulus to the nerve with TMS-of-M1 (mPCMS) in the preactivated tibial anterior muscle (TA). Sixteen healthy adults participated in two sessions (mPCMS, ePCMS), each with 180 pairs of [low-intensity TMS-of-M1 + nerve stimulation] at 0.2Hz. TA motor-evoked potentials (MEP) to single-pulse TMS at pre-PCMS, immediately and 30min after PCMS, were cluster-analyzed to discriminate responders and non-responders. Paired-pulse TMS-of-M1 and F-waves were also tested and BDNF polymorphism influence was explored. Both PCMS protocols significantly increased MEP amplitudes (n = 9 responders each), but the time-course differed with mPCMS inducing larger MEP increase over time. The number of BDNF-methionine carriers tended to be larger than Val66Val in mPCMS and the reverse in ePCMS, thus warranting further investigations. The MEP changes of the preactivated TA likely occurred at the pre-motoneuronal level and larger mPCMS after-effects over time may be related to the afferents recruited. mPCMS seems relevant to be testedin future studies as a painlessnoninvasiveapproach to induce sustained pre-motoneuronal plasticity in spinal cord injury.

Neuronavigated Repetitive Transcranial Stimulation Improves Neurocognitive Functioning in Veterans with Schizophrenia: A Possible Role of BDNF Polymorphism.

It has been reported in the previous literatures that high-frequency (HF) neuronavigated repetitive transcranial magnetic stimulation (rTMS) may improve neurocognitive functioning in patients with schizophrenia. Nonetheless, the heterogeneity of the research findings with regards to the effectiveness of HF-rTMS on the neurocognitive functioning in patients with schizophrenia greatly hinders its clinical application. The current study was designed to determine the predictive role of BDNF variants for neurocognitive improvements after rTMS administration in veterans with schizophrenia. 109 hospitalized veterans with schizophrenia were randomly allocated to active HF-rTMS (n=63) or sham stimulation (n=46) over left DLPFC for 4 consecutive weeks. Neurocognitive functions were assessed by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and at the end of week 4. BDNF polymorphism was genotyped by the technicians. Compared with sham stimulation sessions, the immediate memory performance was significantly increased in active sessions after neuronavigated HF-rTMS administration. In addition, patients with the CC homozygotes demonstrated greater improvement of immediate memory after rTMS treatment, while T allele carriers showed no significant improvement in immediate memory domain relative to baseline performance of immediate memory. Our findings suggest that add-on neuronavigated HF-rTMS is beneficial on immediate memory only in patients with CC homozygotes, but not in T allele carriers. This pilot study provides further evidence for BDNF as a promise biomarker in predicting the clinical response to rTMS stimulation.

Lactoferrin-The Health-Promoting Properties and Contemporary Application with Genetic Aspects.

The aim of the study is to present a review of literature data on lactoferrin's characteristics, applications, and multiple health-promoting properties, with special regard to nutrigenomics and nutrigenetics. The article presents a new approach to food ingredients. Nowadays, lactoferrin is used as an ingredient in food but mainly in pharmaceuticals and cosmetics. In the European Union, bovine lactoferrin has been legally approved for use as a food ingredient since 2012. However, as our research shows, it is not widely used in food production. The major producers of lactoferrin and the few available food products containing it are listed in the article. Due to anti-inflammatory, antibacterial, antiviral, immunomodulatory, antioxidant, and anti-tumour activity, the possibility of lactoferrin use in disease prevention (as a supportive treatment in obesity, diabetes, as well as cardiovascular diseases, including iron deficiency and anaemia) is reported. The possibility of targeted use of lactoferrin is also presented. The use of nutrition genomics, based on the identification of single nucleotide polymorphisms in genes, for example, FTO, PLIN1, TRAP2B, BDNF, SOD2, SLC23A1, LPL, and MTHFR, allows for the effective stratification of people and the selection of the most optimal bioactive nutrients, including lactoferrin, whose bioactive potential cannot be considered without taking into account the group to which they will be given.

Effect of acute exercise intensity on cognitive inhibition and well-being: Role of lactate and BDNF polymorphism in the dose-response relationship.

There is evidence in the literature that acute exercise can modify cognitive function after the effort. However, there is still some controversy concerning the most effective exercise modality to improve cognitive function in acute interventions. Regarding these different exercise modalities, the dose-response relationship between exercise intensity and cognitive response is one of the most challenging questions in exercise and cognition research. In this study, we tested the impact of moderate-intensity (MICT), high-intensity (HIIT) exercise sessions, or control situation (CTRL) on cognitive inhibition (measured with the Stroop Test). Thirty-six young college students participated in this study, where a within-subject repeated measure design was used. ANOVA 2×3 demonstrated that HIIT improved the acute cognitive response to a higher degree when compared to MICT or CTRL (p < 0.05). The cognitive improvements correlated with lactate release, providing a plausible molecular explanation for the cognitive enhancement (r < -0.2 and p < 0.05 for all the Stroop conditions). Moreover, a positive trend in wellbeing was observed after both exercise protocols (HIIT and MICT) but not in the CTRL situation. Genetic BDNF single nucleotide polymorphism did not influence any interactions (p < 0.05). In this sense, our results suggest that exercise intensity could be a key factor in improved cognitive function following exercise in young college students, with no additional impact of BDNF polymorphism. Moreover, our results also provide evidence that exercise could be a useful tool in improving psychological wellbeing.

BDNF rs10501087, rs1491850 and rs11030094 polymorphisms associated with delayed progression in early-stage Parkinson's disease.

Parkinson's disease (PD) is heterogenous in its presentation, progression and response to therapies. Genetic polymorphisms may account for some of this variability. Several single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor gene BDNF have been associated with differing clinical outcomes from different dopaminergic replacement strategies, and one of these, the rs6265 SNP, has been associated with a milder clinical phenotype in the unmedicated, early-stage of PD. We examined if other BDNF SNPs with potential pharmacogenetic effects also are associated with different rates of disease progression. The Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study was analyzed retrospectively. DNA samples (n = 217) were genotyped for the BDNF rs908867, rs11030094, rs10501087, rs1157659, and rs1491850 SNPs, and the primary endpoint was time to initiate symptomatic pharmacotherapy. Genotypes were compared using the Cox proportional hazard ratio (HR) with baseline age, sex, site, time since PD diagnosis and rs6265 genotype as covariates. The primary endpoint was associated with a delay with three SNPs: rs10501087 [HR (95% Confidence Interval) = 28.3 (3.6-223.1, p = 0.002) and 7.6 (1.9-29.8, p = 0.004) for T/T and T/C subjects, respectively, vs. C/C subjects], rs1491850 [HR = 3.3 (1.3-8.4, p = 0.04) and 2.8 (1.3-6.4, p = 0.03) for T/T and T/C subjects, respectively, vs. C/C subjects] and rs11030094 [HR = 2.5 (1.1-5.6, p = 0.03) and 2.0 (1.3-6.4, p = 0.03) for A/A and A/G subjects, respectively, vs. G/G subjects]. From the primary endpoint, specific rs10501087, rs1491850, and rs11030094 SNP genotypes are associated with a slower rate of PD progression in the unmedicated state. A prospective clinical trial examining many BDNF SNPs is warranted.

Are COMT Val158Met (rs4680), DRD2 TaqIA (rs1800497), and BDNF Val66Met (rs6265) polymorphisms associated with executive functions performance at rest and during physical exercise?

Executive functions (EFs) encompass a wide array of cognitive processes, which appear to be influenced by genetic variants of the COMT, DRD2/ANKK1, and BDNF polymorphisms. The present study aimed to investigate whether COMT Val158Met (rs4680), DRD2/ANKK1 (rs1800497), and BDNF Val66Met (rs6265) polymorphisms were associated with EFs assessed at rest and during moderate acute physical exercise. Sixty physically active individuals underwent four laboratory visits. First, they filled out the pre-exercise survey, researchers collected their anthropometric data, and then performed a maximal cardiopulmonary exercise test. In the second and third sessions, participants performed EFs test in a randomized order: while the individual was seated on a cycle ergometer without pedaling (i.e., rest condition); and during physical exercise (pedaling for 30 minutes at moderate intensity before starting the EFs test during exercising). On the fourth day, blood samples were drawn. Our results showed that the response time of the COMT Val homozygotes group was significantly shorter than the COMT Met-carrier group [t(39.78) = 2.13, p = .039,d = 0.56] at rest condition. No significant association was found for the other analyses (DRD2/ANKK1 and BDNF). In conclusion, the present study suggests that COMT Val158Met (rs4680) polymorphisms may be associated with EFs at rest condition. However, further studies are needed to validate this association.

Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain

Background/objectiveChronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. MethodWe aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. ResultsCompared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. ConclusionsThese results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.

Use of COMT and BDNF biomarkers to predict rTMS efficacy for TRD

Background: Registry data documents rTMS remission rates for TRD in the 28-62% range. This heterogeneity of rTMS response underscores a need to identify individual patient characteristics predictive of rTMS efficacy for optimal patient selection. Genetic biomarkers have been proposed. Research documents conflicting results regarding the predictive value of COMT and BDNF polymorphisms for rTMS efficacy in depression. To our knowledge, this study is the largest to date to evaluate the effect of COMT and BDNF genotypes on rTMS efficacy for TRD and the first to evaluate the combined effect of COMT and BDNF. Methods: A retrospective chart review was performed on 95 patients (ages 15-69) with moderate or greater severity MDD (based on DSM-V diagnostic criteria and PHQ-9 score ≥10) who underwent acute rTMS therapy and who submitted saliva for Genomind or Tempus analysis of COMT and BDNF biomarkers. PHQ-9 was assessed at baseline and at end of acute rTMS treatment. Baseline depression and anxiety severity, age, and sex were analyzed to eliminate confounding variables. Results: COMT and BDNF polymorphisms, independently and in combination, were not predictive of rTMS response or remission. BDNF and COMT genotypes were also not significantly associated with PHQ-9 score change. Conclusion: In this clinical population, COMT and BDNF polymorphisms were not predictive of rTMS outcome for TRD. Conflicts of Interest: None to report. Funding: Neuro Wellness Spa

Anxiety Disorders and Prediction of Their Development in Patients with Hypothyroidism and Autoimmune Thyroiditis

Objective: Since the association between thyroid dysfunction and neuropsychiatric disorders has been known for many years, it is important to analyze the associations of the BDNF gene polymorphism (rs6265), the VDR gene polymorphism (rs2228570), and the NMDA gene polymorphism (rs4880213) with the anxiety in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukrainian population and predict the development of anxiety disorders in these patients.&#x0D; Methods: The study involved a total of 153 patients with various forms of thyroid pathology. BDNF levels in the sera of the patients and healthy individuals were quantified using an enzyme-linked immunosorbent assay with a highly sensitive Human BDNF ELISA Kit (Elabscience®, United States, Catalog No: E-EL-H0010) on E.I.A. Reader Sirio S (Seac, Italy). Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA (rs4880213) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System (Bio-Rad Laboratories, Inc., USA). Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA).&#x0D; Results: According to the data obtained when comparing the presence of anxiety on the Hamilton scale on SNP statistically significant differences were revealed depending on BDNF gene polymorphism (rs6265) (p &lt; 0.001). When comparing the presence of anxiety on the Hamilton scale on SNP depending on VDR gene polymorphism (rs2228570), NMDA gene polymorphism (rs4880213) no statistically significant differences were revealed (p = 0.782, p = 0.677 respectively) We identified an inverse strong correlation between the presence of anxiety on Hamilton scale and BDNF, 25-OH Vitamin D levels, and fT4 in the blood (p &lt;0.001) and a direct moderate correlation between the presence of anxiety on Hamilton scale and TSH, GRIN2B, and anti-TPO (p &lt;0.001).&#x0D; Conclusion: Indicators such as BDNF, GRIN2B, fT4, anti-TG, and 25-OH levels of vitamin D are prognostically significant risk criteria for anxiety.

BDNF and KIBRA Polymorphisms Are Related to Altered Resting State Network Connectivity in Middle Age.

Disease-modifying treatments for Alzheimer's disease (AD) may be more successful if interventions occur early, prior to significant neurodegeneration and subsequent to the onset of clinical symptoms, potentially during middle age. Polymorphisms within BDNF, COMT, and KIBRA have been implicated in AD and relate to episodic memory and executive functioning, two domains that decline early in AD. The purpose of the current study was to use an endophenotype approach to examine in healthy, non-demented middle-aged adults the association between polymorphisms in BDNF, COMT, and KIBRA and functional connectivity within networks related to episodic memory and executive function (i.e., default mode network (DMN), executive control network (ECN), and frontoparietal network (FPN)). Resting state networks were identified using independent component analysis and spatial maps with associated time courses were extracted using a dual regression approach. Functional connectivity within the DMN was associated with polymorphisms in BDNF (rs11030096, rs1491850) and KIBRA (rs1030182, rs6555791, rs6555802) (ps < 0.05), ECN connectivity was associated with polymorphisms in KIBRA (rs10475878, rs6555791) (ps < 0.05), and FPN connectivity was associated with KIBRA rs6555791 (p < 0.05). There were no COMT-related differences in functional connectivity of any of the three networks investigated (ps > 0.05). Our study demonstrates that in middle age, polymorphisms in BDNF and KIBRA are associated with altered functional connectivity in networks that are affected early in AD. Future preclinical work should consider these polymorphisms to further elucidate their role in pathological aging and to aid in the identification of biomarkers.

The combined effect between BDNF genetic polymorphisms and exposure to metals on the risk of Chinese dyslexia

BDNF gene has been implicated in the development of cognition and language. Meanwhile, exposure to metals might interact with BDNF gene to increase the risk of neurodevelopmental disorders. The present study aimed to explore the association between BDNF genetic polymorphisms and dyslexic risk and examine whether BDNF polymorphisms would interact with metal exposures, jointly contributing to dyslexia. Among a case-control study composed of 238 children with dyslexia and 228 healthy controls, the BDNF genetic polymorphisms were genotyped by the Sequenom MassARRAY system, and the exposure to eight metals, such as lead (Pb), mercury (Hg) and copper (Cu), were measured using an inductively coupled plasma-mass spectrometer (ICP-MS). Multivariable logistic regression models were used to assess the adjusted odds ratios (ORs) and 95% confidence interval (CI) of dyslexia. After multivariate adjustment, significant associations of dyslexic risk with rs6265 polymorphisms of the BDNF gene were observed (OR = 1.99; 95% CI: 1.15–3.44). Furthermore, exposure to Cu could interact with rs6265 to increase the risk of dyslexia (P interaction = 0.045). High-Cu children with the rs6265 TT genotype were more likely to have dyslexia compared with low-Cu children carrying CC + CT genotypes (OR = 3.19; 95% CI: 1.38–7.39). The findings of this study suggested that the polymorphism of rs6265 in BDNF gene could interact with Cu exposure to increase the occurrence of dyslexia.

BDNF rs6265 Genotype Influences Outcomes of Pharmacotherapy and Subthalamic Nucleus Deep Brain Stimulation in Early-Stage Parkinson's Disease

IntroductionThe efficacy of pharmacotherapy and deep brain stimulation of the subthalamic nucleus in treating Parkinson's disease motor symptoms is highly variable and may be influenced by patient genotype. The relatively common (prevalence about one in three) and protein-altering rs6265 single nucleotide polymorphism (C > T) in the gene BDNF has been associated with different clinical outcomes with levodopa. ObjectiveWe sought to replicate this reported association in early-stage Parkinson's disease subjects and to examine whether a difference in clinical outcomes was present with subthalamic nucleus deep brain stimulation. Materials and MethodsFifteen deep brain stimulation and 13 medical therapy subjects were followed for 24 months as part of the Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152, FDA IDE #G050016). Primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39. ResultsOutcomes with drug therapy in subjects carrying the rs6265 T allele were significantly worse following 12 months of treatment compared to C/C subjects (UPDRS: +20 points, p = 0.019; PDQ-39: +16 points, p = 0.018). In contrast, rs6265 genotype had no effect on overall motor response to subthalamic nucleus deep brain stimulation at any time point; further, rs6265 C/C subjects treated with stimulation were associated with worse UPDRS part II scores at 24 months compared to medical therapy. ConclusionsGenotyping for the rs6265 polymorphism may be useful for predicting long-term response to drug therapy and counseling Parkinson's disease patients regarding whether to consider earlier subthalamic nucleus deep brain stimulation. Validation in a larger cohort of early-stage Parkinson's disease subjects is warranted.

OC18: Transspinal direct current stimulation for pain treatment. Objective proof of concept, initial clinical findings and BDNF polymorphism

Introduction Transspinal Direct Current Stimulation (tsDCS) has been reported to block pain signaling. To approach clinical usage, two studies were performed. In both, the effect of BDNF polymorphism (Val/Met) was investigated. Materials and methods Study I Nineteen healthy controls, the anode over the tenth thoracic vertebra, the cathode over the shoulder. tsDCS: 2.5 A for 20 minutes, double blinded cross over design. Laser Evoked Potentials (LEPs): Stimulation of the dorsum of the hand and foot respectively, recordings at baseline, immediately after- and 30 minutes after the tsDCS stimulation. Amplitude and latency of the N2 peak was assessed and the subjects rated pain intensity. BDNF polymorphism was investigated in DNA from buccal mucosa cells. Study II Patients with neuropathic pain due to polyneuropathy are recruited. tsDCS is given at three days with one day between, BDNF polymorphism investigated as above. Results Study I Group level: LEP amplitudes successively reduced over time. Placebo; latencies unaffected from upper-, slightly increased from lower extremities. Verum; transiently increased from upper-, accumulatively increased from lower extremities in proportion to experienced pain. Individual level: Large variations. BDNF polymorphism influences the effect of stimulation with less pain reduction in those with less active BDNF (Val/Val). Study II Fourteen patients have been investigated. The results will be presented at the conference. Conclusions Short term, anodal thoracic tsDCS affects transspinal pain signaling with large inter-individual differences. Individualized tsDCS may be a treatment option for neuropathic pain. The type of BDNF one carries, seem to influence the effect of stimulation.

Prediction of the Development of Depression in Patients with Autoimmune Thyroiditis and Hypothyroidism

BACKGROUND: Hypothyroidism is frequently accompanied by depression symptoms, whereas depression is considered the most common mental disorder. AIM: It is crucial to analyze the associations of the brain neurotrophic factor (BDNF) gene polymorphism (rs6265), the VDR gene polymorphism (rs2228570), and the NMDA gene polymorphism (rs4880213) with the depression in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukrainian population and predict the development of depressive disorders in these patients. METHODS: The study involved a total of 153 patients with various forms of thyroid pathology. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay with highly sensitive Human BDNF ELISA Kit (Elabscience®, United States, Catalog No: E-EL-H0010) on E.I.A. Reader Sirio S (Seac, Italy). Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA (rs4880213) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™Real-Time Polymerase chain reaction (PCR) Detection System (Bio-Rad Laboratories, Inc., USA). PCR for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). We used the Student’s t-test, ANOVA, Pearson’s Chi-square test, ROC-analysis, odds ratio test, relative odds ratio test. The odds ratio and 95% confidence interval were computed by binary logistic regression. RESULTS: When comparing the presence of depression on the Hamilton scale, statistically significant differences were found depending on BDNF gene polymorphism (rs6265) (p &lt; 0.001), and non-statistically noticeable differences were detected depending on the VDR gene polymorphism (rs2228570) and NMDA gene polymorphism (rs4880213). Our study revealed a marked inverse connection between depression and BDNF levels (p &lt; 0.001) and a reverse moderate correlation between depression and fT4 (p &lt; 0.001) and 25-OH Vitamin D levels (p &lt; 0.001). In addition, we identified a direct moderate correlation between pronounced levels of depression and thyroid-stimulating hormone (TSH) in the blood (p &lt; 0.001). CONCLUSIONS: Indicators such as BDNF, TSH, fT4, anti-TPO, and 25-OH Vitamin D levels were found to be prognostically significant criteria for the risk of developing depression.

Genetic Factors, Brain Atrophy, and Response to Rehabilitation Therapy After Stroke

Objective Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke. Methods The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF val66met and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127). Results Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF val66met carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF val66met polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02). Conclusion Neither the val66met BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF val66met polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer’s disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.

The role of the KIBRA and APOE genes in developing spatial abilities in humans.

In the contemporary high-tech society, spatial abilities predict individual life and professional success, especially in the STEM (Science, Technology, Engineering, and Mathematics) disciplines. According to neurobiological hypotheses, individual differences in cognitive abilities may be attributed to the functioning of genes involved in the regulation of neurogenesis and synaptic plasticity. In addition, genome-wide association studies identified rs17070145 located in the KIBRA gene, which was associated with individual differences in episodic memory. Considering a significant role of genetic and environmental components in cognitive functioning, the present study aimed to estimate the main effect of NGF (rs6330), NRXN1 (rs1045881, rs4971648), KIBRA (rs17070145), NRG1 (rs6994992), BDNF (rs6265), GRIN2B (rs3764030), APOE (rs7412, rs429358), and SNAP25 (rs363050) gene polymorphisms and to assess the effect of gene-environment interactions on individual differences in spatial ability in individuals without cognitive decline aged 18–25 years (N = 1011, 80 % women). Spatial abilities were measured using a battery of cognitive tests including the assessment of “3D shape rotation” (mental rotation). Multiple regression analysis, which was carried out in the total sample controlling for sex, ethnicity and the presence of the “risk” APOE ε4 allele, demonstrated the association of the rs17070145 Т-allele in the KIBRA gene with enhanced spatial ability (β = 1.32; pFDR = 0.037) compared to carriers of the rs17070145 CC-genotype. The analysis of gene-environment interactions revealed that nicotine smoking (β = 3.74; p = 0.010) and urban/rural residency in childhood (β = –6.94; p = 0.0002) modulated the association of KIBRA rs17070145 and АРОЕ (rs7412, rs429358) gene variants with individual differences in mental rotation, respectively. The data obtained confirm the effect of the KIBRA rs17070145 Т-allele on improved cognitive functioning and for the first time evidence the association of the mentioned genetic variant with spatial abilities in humans. A “protective” effect of the APOE ε2 allele on enhanced cognitive functioning is observed only under certain conditions related to childhood rearing.

P.0274 Effect of BDNF polymorphism and dna methylation on reward learning and cognitive performance in major depression

P.0274 Effect of BDNF polymorphism and dna methylation on reward learning and cognitive performance in major depression

DRD2 and BDNF polymorphisms are associated with binge eating disorder in patients with weight regain after bariatric surgery.

The aim of this study was to analyze the association and susceptibility of Single Nucleotide Polymorphisms (SNPs) in the DRD2 and BDNF genes with BED in patients with weight regain in the postoperative period of bariatric surgery. One hundred and seventy-seven individuals who underwent bariatric surgery with weight regain were evaluated and divided into two groups according to the BED diagnostic. The individuals were submitted to an anthropometric evaluation, analysis of the presence of BED using a validated questionnaire, and blood collection for genotyping of the polymorphisms rs6265 (BDNF) and rs1800497 (DRD2) by real-time polymerase chain reaction (RT-PCR). The presence of wild-type alleles for rs1800497 (CC) and rs6265 (GG) was more frequent in patients without BED. Nevertheless, the presence of one or two variant alleles for rs1800497 (CT + TT) and rs6265 (GA + AA) was more frequent in patients with BED. The combination of the two studied SNPs prevailed in patients with BED. The presence of allele frequency of rs1800497 SNP in the DRD2 gene and rs6265 SNP in the BDNF gene, isolated and/or combined, indicated an additional risk for the development of BED in patients with obesity, especially in the context of weight regain. III (evidence obtained from the case-control analytic study).

Polymorphisms of Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 genes in trigeminal neuralgia

SubjectsTrigeminal neuralgia is a neuropathic pain characterized by episodes of severe shock-like pain within the distribution of one or more divisions of the trigeminal nerve. Pain can be influenced by ethnicity, environment, gender, psychological traits, and genetics. Molecules Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 have been involved in mechanisms that underlie pain and neurological conditions. ObjectiveThe aim of this case-control study was to investigate the occurrence of genetic polymorphisms in Nav1.6 sodium channel (SCN8A/rs303810), Brain-derived Neurotrophic Factor (BDNF/rs6265/Val66Met), Catechol-O-methyltransferase (COMT/rs4680/Val158Met), and Guanosine Triphosphate Cyclohydrolase 1 (GCH1/rs8007267) genes in trigeminal neuralgia patients. MethodsNinety-six subjects were divided into two groups: 48 with trigeminal neuralgia diagnosis and 48 controls. Pain was evaluated by visual analog scale and genomic DNA was obtained from oral swabs and analyzed by real-time polymerase chain reaction. ResultsNo association was observed among SCN8A, BDNF, COMT or GCH1 polymorphisms and the presence of trigeminal neuralgia. Genotype distribution and allele frequencies did not correlate to pain severity. ConclusionsAlthough no association of evaluated polymorphisms and trigeminal neuralgia or pain was observed, our data contributes to the knowledge of genetic susceptibility to trigeminal neuralgia, which is very scarce. Further studies may focus on other polymorphisms and mutations, as well as on epigenetics and transcriptional regulation of these genes, in order to clarify or definitively exclude the role of Nav1.6, BDNF, COMT or GCH1 in trigeminal neuralgia susceptibility and pathophysiology.