Neurotrophic Factor Polymorphism Research Articles

Effects of a 6-month dual-task, power-based exercise program on cognitive function, neurological and inflammatory markers in older adults: secondary analysis of a cluster randomised controlled trial.

Functional power-based exercise training can improve physical performance in older adults and cognitive training can improve measures of cognition, but their combined effects on cognition and related risk factors (neurological and inflammatory markers) remains uncertain. This 6-month cluster randomised controlled trial evaluated the effectiveness of dual-task functional power training (DT-FPT) on cognition and circulating neurological and inflammatory markers in older adults at increased falls risk, and whether intervention responses varied by apolipoprotein-E (ApoE) and brain derived neurotrophic factor (BDNF) polymorphisms. Three hundred residents aged ≥ 65 years at increased falls risk residing in 22 independent-living retirement communities, were randomised by village, to DT-FPT (n = 156, 11 villages) involving a multi-component power-based training program performed simultaneously with cognitive and/or motor tasks (45-60 min, 2/week), or a usual care control (CON) group (n = 144, 11 villages). Cognition (computerized CogState battery), inflammatory cytokines, BDNF, insulin-like growth factor-1, vascular endothelial growth factor, amyloid β (1-40) and (1-42) were assessed at baseline and 6-months. Overall, 233 (78%) participants completed the intervention and adherence averaged 50.1%. DT-FPT led to a net 0.18-0.20 SD benefit versus CON in psychomotor ability/attention and reaction time/attention (both P < 0.05). There were no significant intervention effects on circulating markers, except for a net 10.5% benefit in amyloid β (1-40) in DT-FPT versus CON (P < 0.05). Responses were not influenced by APOE or BDNF genotype. In conclusion, DT-FPT in older adults at increased falls risk can provide some cognitive benefits, but these were not related to corresponding changes in inflammatory or neurological markers or influenced by genotype. Australian New Zealand Clinical Trials Registry (ACTRN12613001161718). http://www.anzctr.org.au/ This project was funded by a grant from the National Health and Medical Research Council (NHMRC) Project (APP1046267).

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

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

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

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

A pilot study examining BDNF Val66Met polymorphism and biological sex: Relationships with baseline cognitive functioning in adolescent athletes

The purpose of this exploratory study was to examine interactive relationships between a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and biological sex on cognitive functioning in a sample of healthy adolescent athletes. Participants included 82 student athletes (age: M = 12.85 years, SD = 1.13) who were involved in a clinically-based sports-concussion management program. Athletes completed the ImPACT computerized battery at baseline and provided buccal samples for determination of their BDNF genotype. Two-way ANOVAs were used to evaluate the effect of BDNF genotype (Met+ vs. Met−) and sex (male vs. female) on cognitive functioning (subgroup n’s: Female/Met+ = 12, Female/Met− = 26, Male/Met+ = 12, Male/Met− = 32). ANOVAs revealed non-significant main effects for both BDNF genotype and sex across all four cognitive composites. However, there was a significant BDNF genotype by sex interaction for the visual-motor speed composite (p = .015; ηp 2 = .073), such that female Met carriers demonstrated better performance than male Met carriers. In contrast, no differences were found on visual-motor speed performance between females and males without a Met allele. Although these results will need to be replicated using larger samples, our preliminary findings lend support to the view that the Met allele may be somewhat neuroprotective in healthy adolescent females.

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.

A Common Human Brain-Derived Neurotrophic Factor Polymorphism Leads to Prolonged Depression of Excitatory Synaptic Transmission by Isoflurane in Hippocampal Cultures.

Multiple presynaptic and postsynaptic targets have been identified for the reversible neurophysiological effects of general anesthetics on synaptic transmission and neuronal excitability. However, the synaptic mechanisms involved in persistent depression of synaptic transmission resulting in more prolonged neurological dysfunction following anesthesia are less clear. Here, we show that brain-derived neurotrophic factor (BDNF), a growth factor implicated in synaptic plasticity and dysfunction, enhances glutamate synaptic vesicle exocytosis, and that attenuation of vesicular BDNF release by isoflurane contributes to transient depression of excitatory synaptic transmission in mice. This reduction in synaptic vesicle exocytosis by isoflurane was acutely irreversible in neurons that release less endogenous BDNF due to a polymorphism (BDNF Val66Met; rs6265) compared to neurons from wild-type mice. These effects were prevented by exogenous application of BDNF. Our findings identify a role for a common human BDNF single nucleotide polymorphism in persistent changes of synaptic function following isoflurane exposure. These short-term persistent alterations in excitatory synaptic transmission indicate a role for human genetic variation in anesthetic effects on synaptic plasticity and neurocognitive function.

Pre and postnatal exposure to mercury and sexual development in 9-year-old children in Spain: The role of brain-derived neurotrophic factor

Early exposure to mercury has been related to endocrine disruption. Steroid hormones play a crucial role in neural cell migration, differentiation, etc., as well as protecting against several neurotoxic compounds.We investigate the relation between mercury exposure and children's sexual development, and we evaluate the possible influence of different brain-derived neurotrophic factor (BDNF) polymorphisms on this association.Our study sample comprised 412 9-year-old children participating in the INMA cohort (2004–2015). Mercury concentrations were measured at birth (cord blood) and at 4 and 9 years of age (hair). Sexual development was assessed by levels of sex steroid hormones (estradiol and testosterone) in saliva and the Tanner stages of sex development at 9 years (categorized as 1: prepuberty and >1: pubertal onset). Covariates and confounders were collected through questionnaires during pregnancy and childhood. Polymorphisms in the BDNF gene were genotyped in cord blood DNA. Multivariate linear regression analyses were performed between mercury levels and children's sexual development by sex. Effect modification by genetic polymorphisms and fish intake was assessed.We found marginally significant inverse associations between postnatal exposure to mercury (at 9 years) and testosterone levels (β[95%CI] = -0.16[-0.33,0.001], and −0.20[-0.42,0.03], for boys and girls, respectively). Additionally, we found that prenatal mercury was negatively associated with Tanner stage >1 in boys. Finally, we found significant genetic interactions for some single nucleotide polymorphisms in the BDNF gene.In conclusion, pre and postnatal exposure to mercury seems to affect children's sexual development and BDNF may play a role in this association, but further research would be needed.

Low-dose ketamine infusion for treating subjective cognitive, somatic, and affective depression symptoms of treatment-resistant depression.

Whether the antidepressant effects of low-dose ketamine infusion and the therapeutic impact of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism vary across different depression symptom domains, namely affective, cognitive, and somatic, remains unclear. We-reanalyzed the data of Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression (TRD). A total of 71 patients with TRD were randomized to three infusion groups: 0.5 and 0.2mg/kg ketamine groups and the normal saline placebo group. The Beck Depression Inventory-II (BDI-II) was used to obtain self-reported scores prior to infusion and 240min after infusion and sequentially on days 3, 7, and 14 after infusion. The three-factor model of cognitive, somatic, and affective depressive symptoms that is based on the BDI-II and proposed by Beck et al. was applied in the current study. The Val66Met BDNF polymorphism was genotyped. Ketamine infusion exerted rapid and sustained antidepressant effects on the affective (p=0.014) and cognitive (p=0.005) depression symptom domains but not on the somatic (p=0.085) depression symptom domain. Only patients with TRD harboring any Val allele at the BDNF rs6265 polymorphism were more likely to respond (p=0.011) to low-dose ketamine infusion. Additional studies should elucidate different mechanisms underlying the effects of ketamine infusion on cognitive, affective, and somatic depression symptom domains in patients with TRD.

The Neurobiological Basis of Cognitive Side Effects of Electroconvulsive Therapy: A Systematic Review.

Decades of research have consistently demonstrated the efficacy of electroconvulsive therapy (ECT) for the treatment of major depressive disorder (MDD), but its clinical use remains somewhat restricted because of its cognitive side effects. The aim of this systematic review is to comprehensively summarize current evidence assessing potential biomarkers of ECT-related cognitive side effects. Based on our systematic search of human studies indexed in PubMed, Scopus, and Web of Knowledge, a total of 29 studies evaluating patients with MDD undergoing ECT were reviewed. Molecular biomarkers studies did not consistently identify concentration changes in plasma S-100 protein, neuron-specific enolase (NSE), or Aβ peptides significantly associated with cognitive performance after ECT. Importantly, these findings suggest that ECT-related cognitive side effects cannot be explained by mechanisms of neural cell damage. Notwithstanding, S-100b protein and Aβ40 peptide concentrations, as well as brain-derived neurotrophic factor (BDNF) polymorphisms, have been suggested as potential predictive biomarkers of cognitive dysfunction after ECT. In addition, recent advances in brain imaging have allowed us to identify ECT-induced volumetric and functional changes in several brain structures closely related to memory performance such as the hippocampus. We provide a preliminary framework to further evaluate neurobiological cognitive vulnerability profiles of patients with MDD treated with ECT.

Brain-Derived Neurotrophic Factor Polymorphism and Aphasia after Stroke.

Stroke is one of the most deliberating causes of mortality and disability worldwide. Studies have implicated Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene as a genetic factor influencing stroke recovery. Still, the role of BDNF polymorphism in poststroke aphasia is relatively unclear. This review assesses the recent evidence on the association between the BDNF polymorphism and aphasia recovery in poststroke patients. The article highlights BNDF polymorphism characteristics, speech and language interventions delivered, and the influence of BNDF polymorphism on poststroke aphasia recovery. We conducted a literature search through PubMed and Google Scholar with the following terms: “brain derived-neurotrophic factor” and “aphasia” for original articles from January 2000 until June 2020. Out of 69 search results, a detailed selection process produced a total of 3 articles that met the eligibility criteria. All three studies included Val66Met polymorphism as the studied human BDNF gene. One of the studies demonstrated insufficient evidence to conclude that BDNF polymorphism plays a role in poststroke aphasia recovery. The remaining two studies have shown that Met allele genotype (either single or double nucleotides) was associated with poor aphasia recovery, in either acute or chronic stroke. Carriers of the Val66Met polymorphism of BDNF gave a poorer response to aphasia intervention and presented with more severe aphasia.

Brain-Derived Neurotrophic Factor Polymorphism Influences Response to Single-Pulse Transcranial Magnetic Stimulation at Rest

The ability of noninvasive brain stimulation to modulate corticospinal excitability and plasticity is influenced by genetic predilections such as the coding for brain-derived neurotrophic factor (BDNF). Otherwise healthy individuals presenting with BDNF Val66Met (Val/Met) polymorphism are less susceptible to changes in excitability in response to repetitive transcranial magnetic stimulation (TMS) and paired associative stimulation paradigms, reflecting reduced neuroplasticity, compared to Val homozygotes (Val/Val). In the current study, we investigated whether BDNF polymorphism influences "baseline" excitability under TMS conditions that are not repetitive or plasticity-inducing. Cross-sectional BDNF levels could predict TMS response more generally because of the ongoing plasticity processes. Forty-five healthy individuals (23 females; age: 25.3 ± 7.0 years) participated in the study, comprising two groups. Motor evoked potentials (MEP) were collected using single-pulse TMS paradigms at fixed stimulation intensities at 110% of the resting motor threshold in one group, and individually-derived intensities based on MEP sizes of 1 mV in the second group. Functional variant Val66Met (rs6265) was genotyped from saliva samples by a technician blinded to the identity of DNA samples. Twenty-seven participants (60.0%) were identified with Val/Val, sixteen (35.5%) with Val/Met genotype, and two with Met/Met genotype. MEP amplitudes were significantly diminished in the Val/Met than Val/Val individuals. These results held independent of the single-pulse TMS paradigm of choice (p = 0.017110% group; p = 0.035 1 mV group), age, and scalp-to-coil distances. The findings should be further substantiated in larger-scale studies. If validated, intrinsic differences by BDNF polymorphism status could index response to TMS prior to implementing plasticity-inducing protocols.

Brain derived neurotrophic factor (BDNF) polymorphism rs 10767664 affects metabolic parameters after weight loss secondary to high fat hypocaloric diet with Mediterranean pattern.

We evaluated the effect of the genetic variant rs10767664 of BDNF gene on anthropometric and biochemical changes after weight loss secondary to a high-fat hypocaloric diet with a Mediterranean dietary pattern. A sample of 277 obese subjects was recruited. After subjects met the inclusion criteria, they received a nutritional intervention with a high-fat hypocaloric diet [36% of carbohydrates, 40% of fats (60.0% of monounsaturated fats, 25.0% of saturated fats and 15.0% of polyunsaturated fats) and 24% of proteins]. Biochemical and anthropometric parameters were measured at basal and 3 months. One hundred and seventy-nine subjects (64.6%) had the genotype AA (wild group) and 98 (35.4%) subjects had the next genotypes; AT (81 patients, 29.2%) or TT (17 patients, 6.2%) (Mutant group). The improvement of BMI, weight, fat mass, waist circumference, systolic blood pressure, leptin, total cholesterol and LDL cholesterol was similar in both genotypes after dietary intervention. Secondary to weight loss and only in non-T allele, insulin levels (AA vs. At+TT) (-5.2+0.2 UI/L vs. -2.9+0.3 UI/L: p=0.02) and HOMA-IR (-2.1+0.2 units vs. -1.1+0.1 units: p=0.02) decreased significantly. T allele carriers of the BDNF variant rs10767664 may be an independent predictor of the lack of improvement induced by weight loss on insulin levels and insulin resistance after a high-fat hypocaloric diet with a Mediterranean dietary pattern.

Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue

Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient’s quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.

A-27 APOE & BDNF Polymorphisms Interact to Affect Memory Performance at Baseline in Adolescent Athletes

Abstract Objective Although several single-nucleotide polymorphisms have been associated with cognitive functioning in a variety of healthy and clinical samples, the influence of gene x gene interactions on cognition is poorly understood. The purpose of this study was to examine interactive relationships between apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) polymorphisms on cognitive functioning in a sample of healthy adolescent athletes. Method Participants of this cross-sectional study included 82 athletes (53.7% male, age, M = 12.85, SD = 1.13) who completed the Immediate Post-Concussion and Cognitive Testing (ImPACT) computerized battery at baseline as part of a school-based sports-concussion management program. Athletes also provided a buccal sample for determination of their APOE and BDNF genotypes. Two-way analyses of variance (ANOVAs) were used to evaluate the effect of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) genotypes on the ImPACT cognitive composites. Results ANOVAs showed non-significant main effects for both APOE and BDNF genotypes across the four cognitive composites. However, there was a significant APOE x BDNF genotype interaction for the verbal (p = .01; ηp2 = .08) and visual (p = .013; ηp2 = .08) memory composites, such that ε4+/Met+ carriers demonstrated poorer performance relative to the other allele combinations (ε4+/Met-, ε4−/Met+, ε4−/Met-). No significant interactions were observed for the visual motor speed (p = .20; ηp2 = .02) or reaction time (p = .87; ηp2 &amp;lt; .001) composites. Conclusions Our findings suggest a meaningful relationship between APOE and BDNF genotypes on verbal and visual memory performance in healthy adolescent athletes. These findings will need to be replicated using much larger samples, and future studies will need to explore these associations following sports-related concussion.

TDCS Anodal tDCS increases bilateral corticospinal excitability irrespective of hemispheric dominance

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that utilizes weak direct currents to induce polarity-dependent modulation of corticospinal excitability. Although tDCS exerts a modulatory effect over the stimulation region, several studies have also demonstrated that distal areas of the brain connected to the region of stimulation may also be affected, as well as the contralateral hemisphere. Objective: We examined the effect of a single session of anodal tDCS on corticospinal excitability and inhibition of both the stimulated and non-stimulated hemisphere and examined the influence of these responses by the brain-derived neurotrophic factor (BDNF) polymorphism. Methods: In a randomized cross-over design, changes in corticospinal excitability and inhibition of the stimulated and non-stimulated hemispheres were analysed in 13 participants in both the dominant and non-dominant primary motor cortex (M1). Participants were exposed to 20 min of anodal and sham tDCS and also undertook a blood sample for BDNF genotyping. Results: TMS revealed a bilateral increase in corticospinal excitability irrespective of which hemisphere (dominant vs non-dominant) was stimulated (all P &lt; 0.05). Furthermore, the induction of corticospinal excitability was influenced by the BDNF polymorphism. Conclusion: This finding shows that anodal tDCS induces bilateral effects in corticospinal excitability irrespective of hemispheric dominance. This finding provides scientists and medical practitioners with a greater understanding as to how this technique may be used as a therapeutic tool for clinical populations.

Dissociation of BDNF Val66Met polymorphism on neurocognitive functioning in military veterans with and without a history of remote mild traumatic brain injury

Objective Since neurocognitive functioning following mild traumatic brain injury (mTBI) may be influenced by genetic factors that mediate synaptic survival and repair, we examined the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) on cognition using a well-defined sample of military Veterans with and without a history of mTBI. Method Participants included 138 Veterans (mTBI = 75; military controls [MCs] = 63) who underwent neuropsychological testing, including completion of self-report measures assessing psychiatric distress, and BDNF genotyping. The mTBI group was tested roughly 66.7 months following their most recent mTBI. Veterans were divided into two groups—Met+ (Met/Met and Met/Val; n = 49) and Met− (Val/Val; n = 89) and compared on domain-specific cognitive composite scores representing memory, executive functioning, and visuospatial speed. Results ANCOVAs adjusting for psychiatric distress, sex, years of education, and ethnicity/race revealed a significant group (mTBI vs. MC) by BDNF genotype (Met + vs. Met−) interaction for the memory (p = .024; ηp 2 = .039) and executive functioning (p = .010; ηp 2 = .050) composites, such that Met+ mTBI Veterans demonstrated better performance than Met− mTBI Veterans on the cognitive measures, whereas Met+ MCs demonstrated worse performance relative to Met− MCs on the cognitive measures. No significant interaction was observed for the visuospatial speed composite (p = .938; ηp 2 < .001). Conclusions These findings offer preliminary evidence to suggest that the Met allele may be protective in the context of remote mTBI. Findings need to be replicated using larger samples, and future studies are necessary to elucidate the precise mechanisms and neural underpinnings of this interaction.

Continuous Theta-Burst Stimulation in Children With High-Functioning Autism Spectrum Disorder and Typically Developing Children.

Objectives: A neurophysiologic biomarker for autism spectrum disorder (ASD) is highly desirable and can improve diagnosis, monitoring, and assessment of therapeutic response among children with ASD. We investigated the utility of continuous theta-burst stimulation (cTBS) applied to the motor cortex (M1) as a biomarker for children and adolescents with high-functioning (HF) ASD compared to their age- and gender-matched typically developing (TD) controls. We also compared the developmental trajectory of long-term depression- (LTD-) like plasticity in the two groups. Finally, we explored the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism on cTBS aftereffects in a subset of the ASD group.Methods: Twenty-nine children and adolescents (age range 10–16) in ASD (n = 11) and TD (n = 18) groups underwent M1 cTBS. Changes in MEP amplitude at 5–60 min post-cTBS and their cumulative measures in each group were calculated. We also assessed the relationship between age and maximum cTBS-induced MEP suppression (ΔMEPMax) in each group. Finally, we compared cTBS aftereffects in BDNF Val/Val (n = 4) and Val/Met (n = 4) ASD participants.Results: Cumulative cTBS aftereffects were significantly more facilitatory in the ASD group than in the TD group (PFDR’s < 0.03). ΔMEPMax was negatively correlated with age in the ASD group (r = −0.67, P = 0.025), but not in the TD group (r = −0.12, P = 0.65). Cumulative cTBS aftereffects were not significantly different between the two BDNF subgroups (P-values > 0.18).Conclusions: The results support the utility of cTBS measures of cortical plasticity as a biomarker for children and adolescents with HF-ASD and an aberrant developmental trajectory of LTD-like plasticity in ASD.

Association of GDNF and CNTNAP2 gene variants with gambling.

Background and aimsSome form of gambling can be observed in nearly every society, as the gratification felt upon winning in uncertain conditions is universal. A culturally distinct form of gambling, associated with a traditional sporting event of archery known as “teer,” is innate to the province of Meghalaya, India. The objective of this study was to find genetic variants underlying this unique form of behavioral addiction. To better understand game-based gambling, we studied genetic variants related to dopaminergic pathways and other genes previously linked to various psychological disorders.MethodsThis study was carried out on a sample of 196 Indo-Aryan adults from Shillong, Meghalaya. Genotyping of glial cell line-derived neurotrophic factor (GDNF) polymorphisms was carried out using real-time PCR. We further investigated 32 single nucleotide polymorphisms located in the 3′ UTR of additional genes of interest using an OpenArray® real-time PCR platform.ResultsCase–control analysis revealed a significant association between GDNF variant rs2973033 (p = .00864, χ2 = 13.132, df = 2) and contactin-associated protein-like 2 (CNTNAP2) variant rs2530311 (p = .0448, χ2 = 13.132, df = 2) with gambling.Discussion and conclusionsAssociation of the GDNF gene with gambling could be attributed to its involvement in the development and survival of dopaminergic neurons. Our result is in good agreement with previous data indicating the role of GDNF in certain substance addictions. Several rare variants in the CNTNAP2 gene were also implicated in alcohol addiction in a previous study. This pilot study provides further support for the role of GDNF and CNTNAP2 in addiction behaviors.

IS BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) VAL66MET POLYMORPHISM ASSOCIATED WITH OBSESSIVE-COMPULSIVE DISORDER? A META-ANALYSIS

Brain-derived neurotrophic factor (BDNF) polymorphism plays an important role in neural survival and was proposed to be related to obsessive-compulsive disorder (OCD). Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in OCD have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with OCD and age-matched controls. Electronic databases were searched for eligible articles in English and ten studies on the association of the BDNF Val66Met polymorphism with OCD were analysed. A total of ten studies involving 2306 cases with OCD and 4968 healthy controls were included. Findings indicated that the BDNF Val66Met polymorphism was not associated with OCD. But there was a marginally significant effect of the BDNF Val66Met variant on OCD in different ethnicity. Findings from this meta-analytic investigation of published literature provide little support for the Val66Met variant of BDNF as a predictor of OCD. Future well-powered agnostic genome-wide association studies with more refined phenotype are needed to clarify genetic influences on OCD.

BDNF Val66Met polymorphism and cognitive impairment in Parkinson's disease-a meta-analysis.

Conflicting results identifying the association between Brain-derived neurotrophic factor (BDNF) polymorphism, Val66Met, and cognitive impairment in Parkinson's disease (PD) have been reported. To clarify whether Val66Met is related to cognitive impairment in PD, we carried out this meta-analysis by searching literature from PubMed, Web of Science, and Embase databases regarding this polymorphism. Six eligible studies involving 1467 PD patients were included in this meta-analysis. Our results showed statistically significant association between Val66Met and risk of cognitive impairment in PD patients in additive model (Met/Met vs. Val/Val: OR 3.82, 95%CI 1.32 to 11.08, p = 0.01) and recessive model (Met/Met vs. Val-carrier: OR 3.81, 95%CI 1.38 to 10.53, p = 0.01) except for dominant model. Our meta-analysis implicates Val66Met BDNF polymorphism may be associated with Parkinson's disease cognitive impairment, further well-designed studies with larger populations are required to validate these results owing to the limited research.