BDNF Val66Met Research Articles

BDNF (rs6265) Val < Met polymorphism can buffer cognitive functions against post stroke CT/MRI pathological findings

Brain lesions following stroke have been shown prevalently in CT/MRI, and it was confirmed that lesions usually are accompanied by cognitive deficits. Although previous studies have emphasized that BDNF Val66Met polymorphism had a substantial role in neurogenesis and synaptic plasticity, it remains unclear to what extent an interaction may be appeared between neuroimaging findings and Val66Met variants on different cognitive functions following stroke. In a case-control study the carriers of at least one Val allele (n = 56), were compared with the carriers of Met/Met homozygotes (n = 156) in order to find possible neuroimaging factors in relation to cognitive functions in a sample from the north of Iran. The third edition of Addenbrooke’s Cognitive Examination (ACE-III) was used to determine the cognitive functions. There were interactive effects among Val66Met genotypes with dominant hemisphere lesions [F = 6.97, ή 2 = 0.03, p = 0.009], cerebral atrophy [F = 5.43, ή 2 = 0.03, p = 0.011] and number of lesions [F = 4.32, ή 2 = 0.04, p = 0.014], for visuospatial skills, memory, and attention functions respectively; implying that the effect of dominant hemisphere lesions, cerebral atrophy, and multiple lesions on cognitive functions have been modulated by Met/Met homozygosity. The destructive effect of Val/Met homozygosity on cognitive functions was shown to be exacerbated by dominant hemispheric lesions, cerebral atrophy, and multiple lesions following stroke. The findings of present research support our hypothesis that interaction of Val66Met variants with cerebral lesions is associated with cognitive dysfunctions in post stroke conditions; particularly through Met/Met homozygosity which act as a buffer mechanism against some CT/MRI pathological findings.

Effects of BDNF Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations.

Objective The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD. Methods Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics. Results The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II. Conclusion Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.

Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis

BackgroundThe BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP). MethodMulti-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses. ResultsAfter applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype. ConclusionsOur results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.

Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-\u03b54 in middle-age cognitively unimpaired individuals from the ALFA study

BackgroundCurrent evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders. However, it remains to be elucidated whether there is an impact of BDNF Val66Met polymorphism on the volumes of the hippocampal subfield volumes (HSv) in cognitively unimpaired (CU) individuals, and the interactive effect with the APOE-ε4 status.MethodsBDNF Val66Met and APOE genotypes were determined in a sample of 430 CU late/middle-aged participants from the ALFA study (ALzheimer and FAmilies). Participants underwent a brain 3D-T1-weighted MRI scan, and volumes of the HSv were determined using Freesurfer (v6.0). The effects of the BDNF Val66Met genotype on the HSv were assessed using general linear models corrected by age, gender, education, number of APOE-ε4 alleles and total intracranial volume. We also investigated whether the association between APOE-ε4 allele and HSv were modified by BDNF Val66Met genotypes.ResultsBDNF Val66Met carriers showed larger bilateral volumes of the subiculum subfield. In addition, HSv reductions associated with APOE-ε4 allele were significantly moderated by BDNF Val66Met status. BDNF Met carriers who were also APOE-ε4 homozygous showed patterns of higher HSv than BDNF Val carriers.ConclusionTo our knowledge, the present study is the first to show that carrying the BDNF Val66Met polymorphisms partially compensates the decreased on HSv associated with APOE-ε4 in middle-age cognitively unimpaired individuals.

Quality of life 6 and 18 months after mild traumatic brain injury in early childhood: An exploratory study of the role of genetic, environmental, injury, and child factors

Mild traumatic brain injury (mTBI) in early childhood is prevalent, and some children may be at risk for short- and long-term difficulties that could affect quality of life (QoL). Despite growing efforts to understand associations between potential risk factors and outcomes after injury, prognosis is elusive and lacks the inclusion of genetic variables which may convey additional predictive power. This study assessed which factors contribute to pediatric QoL 6 and 18 months post-recruitment in 159 participants (mTBI = 52; orthopedic injury [OI] = 43; typically developing controls [TDC] = 64) aged 18 to 60 months at the time of injury (M = 37.50, SD = 11.69). Family environment, injury characteristics, and child cognitive-behavioral functioning were assessed at 6 months via parent questionnaires and socio-cognitive assessment. QoL was determined using the Pediatric Quality of Life Inventory at both time points. Genetic information (Brain-derived neurotrophic factor [BDNF] genotype) was collected using saliva samples. Hierarchical regression analyses testing biological, family-environmental, injury and cognitive-behavioral factors revealed that the BDNF Val66Met polymorphism was a significant independent predictor of better QoL 6 months post-injury in the mTBI group. Lower parental distress significantly and independently predicted higher QoL 18 months after mTBI, and 6 months post-recruitment in the TDC group. At 18 months, models were non-significant for both control groups. Genetic factors involved in neuroplasticity may play an important role in recovery 6 months after mTBI and contribute to outcome via their interplay with environmental factors. Over time, family factors appear to become the primary determinants of post-mTBI outcome.

Pain catastrophizing is associated with the Val66Met polymorphism of the brain-derived neurotrophic factor in fibromyalgia

BackgroundFibromyalgia (FM) is a musculoskeletal chronic pain syndrome that impacts negatively patient’s daily lives. Its pathogenesis is characterized by a complex relationship between biological and psychosocial factors not fully understood yet. Pain catastrophizing is associated with FM and is an important predictor of outcomes. This study aimed to answer two questions: (i) whether the allele and genotype frequencies of BDNF Val66Met (rs6265) polymorphism differs between FM patients and healthy controls (HC); and (ii) if the BDNF Val66Met polymorphism is a factor that predicts pain catastrophizing in FM.MethodsIn a cross-sectional design, 108 FM patients and 108 HC were included. FM patients responded to the Brazilian Portuguese version of the Pain Catastrophizing Scale (BP-PCS) to assess pain catastrophizing, as well as other validated tools for anxiety (The State-Trait Anxiety Inventory - STAI), depression (Beck Depression Inventory II – BDI-II) and functional aspects (Fibromyalgia Impact Questionnaire - FIQ; Central Sensitization Inventory validated and adapted for Brazilian population - CSI-BP; Pittsburgh Sleep Quality Index - PSQI; and Resilience Scale). All subjects were genotyped for the BDNF Val66Met polymorphism.ResultsVal allele was significantly more frequent in FM patients compared to the control group (p < 0.05). Also, FM patients with Val/Val genotype showed more pain catastrophizing thoughts, and this genotype was significantly associated with magnification and rumination dimensions of BP-PCS (p < 0.05). Furthermore, there were significant differences in levels of anxiety and symptoms of depression, years of education, and the functional situation between the FM and control groups.ConclusionsThe findings show an association of BDNF Val66Met polymorphism with pain catastrophizing in FM, which opens new avenues to comprehend the interplay between molecular genetic characteristics and neuroplasticity mechanisms underpinning FM.

The impact of BDNF Val66Met on cognitive skills in veterans with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a trauma-induced disorder characterized with impaired cognitive function. BDNF modulates cognition and is involved in neuroprotection and neurocognitive processing. The BDNF Val66Met polymorphism was found to influence cognitive functions. In PTSD, carriers of the BDNF GG genotype had better spatial processing of navigation performance, and lower hyperarousal and startle reaction than A allele carriers. The hypothesis was that veterans with PTSD, carriers of the BDNF Val66Met A allele, will show reduced cognitive skills.The study included 315 male Caucasian combat veterans, with (N = 199) or without (N = 116) current and chronic PTSD. Cognition was assessed using the Rey-Osterrieth Complex Figure (ROCF) test that determines visual-spatial perception and short and long-term visual memory function.The results revealed that cognitive decline measured with ROCF test was associated with PTSD. Presence of the BDNF Val66Met GG genotype in veterans with PTSD, but not in veterans without PTSD, showed protective association with visual short-term memory and visual object manipulation after few seconds (executive function), assessed with the ROCF immediate recall test, compared to the A carriers with PTSD.In conclusion, this was the first study to confirm the association between BDNF Val66Met and memory and attention performed with ROCF in male veterans with PTSD. The results corroborated that the BDNF Val66Met A allele, compared to GG genotype, is associated with poorer short-term visual memory and attention linked with executive functions, in veterans with PTSD.

0043 BDNF Genotype Modulates Circadian Response to Simulated Nightwork in IL-6

Abstract Introduction Brain Derived Neurotrophic Factor (BDNF) is involved in synaptic plasticity and may be involved in sleep and circadian regulation. The BDNF gene has a single nucleotide polymorphism (Val66Met) resulting in decreased BDNF secretion. The Met allele is associated with reduced nocturnal slow wave activity following sleep loss, and may also enable more flexible adaptation to circadian misalignment. We used IL-6, a pleiotropic cytokine with biphasic circadian secretion, to compare the response of Val and Met carriers to circadian misalignment. Methods 15 healthy men (26.7±4.9y) participated in a 16-day laboratory study of simulated nightwork with two nighttime duty cycles and an intervening 58h restart break. The study began with two baseline 10h time in bed (TIB) nighttime sleep opportunities (22:00-08:00) and a 5h TIB afternoon nap (15:00-20:00). Each duty cycle consisted of five nighttime waking periods and four 10h TIB daytime sleeps (10:00-20:00). The restart break began with a 5h TIB morning nap (10:00-15:00), followed by two 10h TIB nighttime sleeps (22:00-08:00). The middle two daytime sleep periods from each duty cycle were monitored polysomnographically and visually scored. During the baseline and restart periods, blood samples were collected at 08:25 and then at 2h intervals until 20:00. Plasma IL-6 was measured by means of ELISA. BDNF Val66Met genotype was determined from whole blood. Results The genotype distribution was in Hardy-Weinberg equilibrium (Val/Val:5; Val/Met:10; Met/Met:0). On average, Met carriers slept 52.2min longer (p=0.052) and displayed 27.7min more REM (p=0.013) than Val/Val subjects during the 10h TIB daytime sleeps. Baseline IL-6 concentrations were similar between genotypes. However, during the restart break, Val/Met subjects showed reduced IL-6 compared to baseline and to Val/Val subjects (p=0.022). Conclusion BDNF Val66Met heterozygotes exhibited blunted IL-6 levels following simulated nightwork, suggesting this genotype experienced a substantial circadian shift and/or altered response to sleep loss associated with daytime sleep. Support FMCSA award DTMC75-07-D-00006; Elliot D. Weitzman, M.D. Research Grant from the Sleep Research Society Foundation.

Effect of Functional BDNF and COMT Polymorphisms on Symptoms and Regional Brain Volume in Frontotemporal Dementia and Corticobasal Syndrome.

The authors examined the effects of two common functional polymorphisms-brain-derived neurotrophic factor (BDNF) Val66Met and catechol-O-methyltransferase (COMT) Val158Met-on cognitive, neuropsychiatric, and motor symptoms and MRI findings in persons with frontotemporal lobar degeneration (FTLD) syndromes. The BDNF Val66Met and COMT Val158Met polymorphisms were genotyped in 174 participants with FTLD syndromes, including behavioral variant frontotemporal dementia, primary progressive aphasia, and corticobasal syndrome. Gray matter volumes and scores on the Delis-Kaplan Executive Function System, Mattis Dementia Rating Scale, Wechsler Memory Scale, and Neuropsychiatric Inventory were compared between allele groups. The BDNF Met allele at position 66 was associated with a decrease in depressive symptoms (F=9.50, df=1, 136, p=0.002). The COMT Val allele at position 158 was associated with impairment of executive function (F=6.14, df=1, 76, p=0.015) and decreased bilateral volume of the head of the caudate in patients with FTLD (uncorrected voxel-level threshold of p<0.001). Neither polymorphism had a significant effect on motor function. These findings suggest that common functional polymorphisms likely contribute to the phenotypic variability seen in patients with FTLD syndromes. This is the first study to implicate BDNF polymorphisms in depressive symptoms in FTLD. These results also support an association between COMT polymorphisms and degeneration patterns and cognition in FTLD.

The BDNF Val66Met Polymorphism, Regular Exercise, and Cognition: A Systematic Review.

The purpose of this study was to synthesize research evidence from studies on the relationships among the BDNF Val66Met polymorphism, regular exercise, and cognition in human subjects. PubMed, CINAHL, and Web of Science were searched systematically. Search limiters applied in these databases included humans, English language, time limits from 2009 to 2019, and peer-reviewed journal articles. Eight studies were included in the current review. While there was some evidence to tentatively suggest that greater levels of exercise were associated with certain forms of memory in Val/Val homozygotes than Met carriers, more research is needed to corroborate these findings. Regarding attention/information processing speed, executive function as well as global cognition, the evidence is either inconsistent or sparse and does not allow for tentative conclusions. Compelling evidence from high-quality clinical trials is needed to re-examine the relationship between the BDNF Val66Met polymorphism, exercise, and cognition.

Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial.

Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression. The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects. The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively. These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation.

Interactions between the combined genotypes of 5-HTTLPR and BDNF Val66Met polymorphisms and parenting on adolescent depressive symptoms: A three-year longitudinal study

BackgroundThe importance of multiple genes-environment interaction (G × E) has been highlighted in studies on depressive symptoms. 5-HTTLPR and BDNF Val66Met polymorphisms, with functional interconnection, have been implicated in the pathophysiology of depressive symptoms. However, little is understood about whether the interaction of 5-HTTLPR, BDNF Val66Met and parenting fits better with the epistatic or cumulative manner. Methods865 adolescents (T1: Mage = 12.32, 50.2% girls) were included in a three-year interval longitudinal design. Standardized questionares about parenting and depressive symptoms were collected. Saliva samples were collected for genotyping. ResultsNeither the concurrent nor longitudinal interaction of 5-HTTLPR, BDNF Val66Met and parenting (G × G × E) showed significant effects on depressive symptoms. The interaction between cumulative genotypes and positive parenting (CG × E) was significant, with the strong differential susceptibility model, for depressive symptoms concurrently but not longitudinally after statistical correction. Adolescents who carried 3 (i.e. SS and Val/Met, L allele and Val/Val) and 4 (i.e. SS and Val/Val), not 1 (i.e. L allele and Met/Met) or 2 cumulative susceptibility alleles (i.e. SS and Met/Met, L allele and Val/Met), reported fewer depressive symptoms if they had experienced higher levels of positive parenting, and more symptoms under lower levels of positive parenting. LimitationsThis study did not examine the 5-HTTLPR triallelic (rs25531) marker and did not include an external sample. ConclusionsThe combined effects of 5-HTTLPR and BDNF Val66Met polymorphisms functioned in a manner of cumulative rather than epistatic in response to positive parenting on early adolescent depressive symptoms.

Association of brain-derived neurotrophic factor (Val66Met) polymorphism with the risk of Parkinson’s disease and influence on clinical outcome

Parkinson’s disease (PD) is a common neurodegenerative disease. Motor symptoms of rigidity, tremor, and bradykinesia and non-motor symptoms like the cognitive deficit, autonomic dysfunction, dementia, anxiety and depression all contribute to morbidity. Emerging shreds of evidence suggest the role of BDNF (Val66Met) polymorphism in PD risk and associated cognitive deficit. Hence, the current study is aimed to investigate the role of BDNF Val66Met in the risk of PD development and associated cognitive abnormalities. A total of 269 PD cases and 271 healthy, age, ethnicity and gender matched controls were recruited in the study. Genomic DNA was isolated, amplified and SNP was identified using the RFLP method and validated by Sanger’s sequencing. There was a significant association of BDNF Val66Met with PD risk in both Dominant and recessive models (GG vs GA+AA: OR: 1.47, CI: 1.04-2.09, P =0.03, GG+GA vs AA: OR: 2.32, CI: 1.07-5.00, P =0.02). The main nonmotor symptom i.e. cognitive impairment was significantly associated with the variant genotype of BDNF Val66Met Polymorphism (GG vs GA+AA: OR: 1.47, CI: 1.04-2.09, P =0.03, GG+GA vs AA: OR: 2.32, CI: 1.07-5.00, P =0.02).We found a significant association of variant genotype with disease severity, the activity of daily living as assessed by S &amp; E score as it was found to better with wild genotype and a significant decrease in quality of life with homozygous mutant genotype. We did not find significant differences in disease duration, absolute levodopa response among the genotypes. Our results implicate BDNF Val66Met polymorphism is associated with the risk of PD, cognitive impairment, poor quality of life and greater disease severity in PD.

Supplemental Material for BDNF Val66Met Polymorphism to Generalized Anxiety Disorder Pathways: Indirect Effects via Attenuated Parasympathetic Stress-Relaxation Reactivity

Supplemental Material for BDNF Val66Met Polymorphism to Generalized Anxiety Disorder Pathways: Indirect Effects via Attenuated Parasympathetic Stress-Relaxation Reactivity

Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome.

BackgroundThe prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.MethodsA total of 611 patients with recent ACS were recruited at a university hospital in Korea. Baseline evaluations from 2007 to 2012 assessed BDNF val66met polymorphism and personality using the Big Five Inventory, which yielded two personality clusters (resilient and vulnerable) and five dimensions (extraversion, agreeableness, conscientiousness, neuroticism, and openness). Over a 5~12 year follow-up after the index ACS, times to MACE were investigated using Cox regression models after adjustment for a range of covariates.ResultsThe BDNF val66met polymorphism modified the associations between vulnerable personality type and worse long-term cardiac outcomes in ACS patients with significant interaction terms, in that the associations were statistically significant in the presence met allele. Similar findings were observed for the individual personality dimensions of agreeableness and neuroticism.ConclusionsGene (BDNF val66met polymorphism) x environment (personality traits) interactions on long-term cardiac outcomes were found in ACS.

BDNF Val66Met Positive Players Demonstrate Diffusion Tensor Imaging Consistent With Impaired Myelination Associated With High Levels of Soccer Heading: Indication of a Potential Gene-Environment Interaction Mechanism.

The purpose of this study was to examine the potential effect modifying role of the BDNF Val66Met polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas. At enrollment and 2 years later, total heading in the prior 12 months (12-mo.) was estimated using an established self-report instrument and diffusion tensor imaging (DTI) was performed. Generalized Estimating Equations (GEE) logistic regression models were employed to test effect modification by the BDNF Val66Met polymorphism on the association between 12-mo. heading exposure and DTI. We identified a significant interaction of 12-mo heading*BDNF Val66Met genotype on the presence of low Radial Diffusivity, a DTI marker associated with myelination. Only Met (+) players demonstrated significantly reduced odds of low RD [OR (95 % CI): −2.36 (−3.53, −1.19)] associated with the highest vs. lowest quartile of 12-mo heading exposure. BDNF Val66Met (+) soccer players with long-term exposure to high levels of heading exhibit less low Radial Diffusivity, suggesting impaired re-myelination may be a substrate of the previously reported association between heading and poor functional outcomes in soccer players.

MARKERS AND BIOMARKERS OF DEMENTIA BDNF GENOTYPE AND CHANGES IN WHITE MATTER HYPERINTENSITIES AND HIPPOCAMPAL MICROSTRUCTURE IN OLDER MEN AND WOMEN

Brain-derived neurotrophic factor (BDNF) may protect against cerebral gray and white matter impairments in older age. The val66met genetic polymorphism of BDNF is recently emerging as an early marker of brain structural integrity. However, evidence is sparse, cross-sectional, and mostly in men. In a longitudinal cohort study of community-dwelling older adults (N=139, mean age=81.6, 58% female, 58% white, mean follow-up=3.4 years), we estimated the overall and sex-stratified effects of BDNF val66met polymorphism on changes in cognition and gray and white matter macro- and micro-structure. Annualized percent change was computed for volume of white matter (WM) hyperintensities and gray matter (GM), fractional anisotropy of normal appearing WM, and mean diffusivity (MD) of GM in whole brain and memory and executive control function networks. Significant associations were adjusted for variables differing by genotype (race, APOE4, diabetes, triglycerides, smoking). Compared to met carriers, val homozygotes had slower annual whole brain WMH accrual (median (IQR) 31.4% (61.7) vs. 60.7% (92.4)), stronger in women. Met carriers had slower annual accrual of hippocampal MD (median (IQR) 1.26% (0.92) vs. 1.85% (1.09) for right hippocampus, stronger for women, and 1.45% (1.06) vs. 1.97% (1.22) for left hippocampus, stronger for men) compared to val homozygotes. Associations were robust to covariates’ adjustment. BDNF polymorphism was not associated with cognitive changes. BDNF polymorphism may help in early identification of those more likely to resist accrual of WMH and loss of hippocampal microstructural integrity, with effects varying by sex.

An Increase of Excitatory-to-Inhibitory Synaptic Balance in the Contralateral Cortico-Striatal Pathway Underlies Improved Stroke Recovery in BDNF Val66Met SNP Mice

Despite negative association in cognition and memory, mice harboring Val66Met BDNF SNP (BDNFM/M) exhibit enhanced motor recovery accompanied by elevated excitatory synaptic markers VGLUT1 and VGLUT2 in striatum contralateral to unilateral ischemic stroke. The cortico-striatal pathway is a critical gateway for plasticity of motor/gait function. We hypothesized that enhanced excitability of the cortico-striatal pathway, especially of the contralateral hemisphere, underlies improved motor recovery. To test this hypothesis, we examined the key molecules involving excitatory synaptogenesis: Thrombospondins (TSP1/2) and their neuronal receptor α2δ-1. In WT brains, stroke induced expressions of TSP1/2-mRNA. The contralateral hemisphere of BDNFM/M mice showed heightened TSP2 and α2δ-1 mRNA and protein specifically at 6 months post-stroke. Immunoreactivities of TSPs and α2δ-1 were increased in cortical layers 1/2 of stroked BDNFM/M animals compared with BDNFM/M sham brains at this time. Areal densities of excitatory synapses in cortical layer 1 and striatum were also increased in stroked BDNFM/M brains, relative to stroked WT brains. Notably, the frequency of GABAergic synapses was greatly reduced along distal dendrites in cortical layer 1 in BDNFM/M brains, whether or not stroked, compared with WT brains. There was no effect of genotype or treatment on the density of GABAergic synapses onto striatal medium spiny neurons. The study identified molecular and synaptic substrates in the contralateral hemisphere of BDNFM/M mice, especially in cortical layers 1/2, which indicates selective region-related synaptic plasticity. The study suggests that an increase in excitatory-to-inhibitory synaptic balance along the contralateral cortico-striatal pathway underlies the enhanced functional recovery of BDNFM/M mice.

The role of single nucleotide polymorphism Val66Met in BDNF gene in the formation of end points after ST segment elevation myocardial infarction

The purpose of this study was to research the possible associations of single-nucleotide polymorphism of Val66Met BDNF gene with the occurrence of endpoints after 6 months of follow-up after a myocardial infarction with ST elevation segment — ST segment elevation myocardial infarction (STEMI). To participate in the study, 256 patients which met all the inclusion criteria were hospitalized in the department of intensive care, State Institution “L. T. Malaya Therapy National Institute NAMSU” from January 2016 to February 2019. Blood fl ow to all patients was restored at the level TIMI III. The frequency of genotypes Val66Met gene for BDNF in STEMI patients (n = 256) was the following: 66ValVal — 74.2 % (n = 190), 66ValMet + 66MetMet — 25.8 % (n = 66). The study of single-nucleotide polymorphism of Val66Met gene BDNF (rs6265) was performed by real-time polymerase chain reaction using the “TacMan TMSNP Genotyping Assays” production of Thermo Fisher Scientifi c Assay IDC_11592758_1. The emotional state of the patients and its relationship with stress were assessed with the questionnaire “Depression, Anxiety and Stress Scale-21”. It turned out that the 66ValMet + 66MetMet polymorphism of the BDNF gene, stress and anxiety 10—14 days before the event, as well as reduced left ventricular ejection fraction, are associated with an unfavorable prognosis of the combined end point 6 months after STEMI and are its independent predictors.

Interaction between the BDNF Val66Met polymorphism and childhood trauma on cortical functional network in non-clinical adults

Interaction between the BDNF Val66Met polymorphism and childhood trauma on cortical functional network in non-clinical adults