Neurotrophic Factor Gene Val66Met Polymorphism Research Articles

Effect of the brain-derived neurotrophic factor gene Val66Met polymorphism on sensory-motor integration during a complex motor learning exercise

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism may cause impairment in short-term motor learning by reducing activity-dependent BDNF expression, which causes alterations in synaptic plasticity by changing glutamatergic and GABAergic synaptic transmissions. Sensory-motor integration (SMI) plays an important role in motor learning. In this study, we investigated the role of this polymorphism on SMI during a complex motor learning practice. Forty-three healthy participants performed standardized 5-day basketball shooting exercises under supervision. Electrophysiologic SMI studies were performed before the first day exercise (T0) and after the first and fifth day exercises (T1 and T2, respectively). SMI was studied using electrical median nerve stimulation at the wrist, followed by transcranial magnetic stimulation (TMS) of the contralateral motor cortex with various inter-stimulus intervals (ISIs). Recordings were made from the thenar and forearm flexor muscles. Participants were divided into two groups according to their BDNF genotype. Group 1 consisted of 26 subjects with the Val66Val genotype and group 2 included 17 subjects with the BDNF Met allele. Group 2 had a lower increase in basketball scores at day 5. Moreover, they had higher afferent facilitation for the responses recorded from both thenar and forearm flexor muscles at T1, but these changes could not be maintained until T2. This non-persistent early hyper-responsivity of the sensory-motor cortex in subjects with the BDNF Met allele might be explained by a transient upsurge of cortical excitability to compensate the insufficient cortical plasticity during motor learning, which could be considered as a sign of lower performance in motor skill learning.

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Is a Risk Factor for Attention-Deficit Hyperactivity Disorder in a Turkish Sample

ObjectiveAttention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD.MethodsTwo hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher's Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms.ResultsThe GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes.ConclusionWe found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism and Risk of Schizophrenia: A Meta-analysis of Case-Control Studies.

According to evidences from previous family and association studies, it has been claimed that genetic factors are involved in the neuropathogenesis of Schizophrenia disorder. Whether the Val66Met variant of brain-derived neurotrophic factor (BDNF) gene plays any roles in the pathogenesis of this syndrome or could be a potential biomarker for prognosis of this disorder has been a long-standing controversial issue. We performed a meta-analysis restricted to case-control studies and searched Pubmed, PsychInfo, and Google scholar using keywords including 'association,' 'Val66Met,' 'BDNF,' and 'schizophrenia' published up to May 1, 2015. A total of 39 studies for schizophrenia were combined by fixed- and random-effects models. The pooled results from the schizophrenia sample indicated no significant evidence for the association of Val/Val and Val/Met genotypes of BDNF gene with schizophrenia, but it was observed that there is an association between Met/Met polymorphism and schizophrenia in Asian, European, and Chinese populations, this means that the risk of schizophrenia in Asian, European, and Chinese populations with Met/Met genotype is, respectively, 9, 26, and 9%. There was a significant association between BDNF Val66Met polymorphism and schizophrenia in our meta-analysis study. We cannot rule out the possibility that other polymorphisms in the BDNF gene are involved in the pathophysiology of schizophrenia. In addition, more studies should be conducted on the polymorphisms in other genes to elucidate their possible roles in schizophrenia.

Association of brain-derived neurotrophic factor gene Val66Met polymorphism with primary dysmenorrhea.

Primary dysmenorrhea (PDM), the most prevalent menstrual cycle-related problem in women of reproductive age, is associated with negative moods. Whether the menstrual pain and negative moods have a genetic basis remains unknown. Brain-derived neurotrophic factor (BDNF) plays a key role in the production of central sensitization and contributes to chronic pain conditions. BDNF has also been implicated in stress-related mood disorders. We screened and genotyped the BDNF Val66Met polymorphism (rs6265) in 99 Taiwanese (Asian) PDMs (20–30 years old) and 101 age-matched healthy female controls. We found that there was a significantly higher frequency of the Met allele of the BDNF Val66Met polymorphism in the PDM group. Furthermore, BDNF Met/Met homozygosity had a significantly stronger association with PDM compared with Val carrier status. Subsequent behavioral/hormonal assessments of sub-groups (PDMs = 78, controls = 81; eligible for longitudinal multimodal neuroimaging battery studies) revealed that the BDNF Met/Met homozygous PDMs exhibited a higher menstrual pain score (sensory dimension) and a more anxious mood than the Val carrier PDMs during the menstrual phase. Although preliminary, our study suggests that the BDNF Val66Met polymorphism is associated with PDM in Taiwanese (Asian) people, and BDNF Met/Met homozygosity may be associated with an increased risk of PDM. Our data also suggest the BDNF Val66Met polymorphism as a possible regulator of menstrual pain and pain-related emotions in PDM. Absence of thermal hypersensitivity may connote an ethnic attribution. The presentation of our findings calls for further genetic and neuroscientific investigations of PDM.

Brain‐derived neurotrophic factor gene Val66Met polymorphism and cognitive function in obsessive–compulsive disorder

In the present study, we have tested the hypothesis that brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism is associated with obsessive-compulsive disorder (OCD) and also investigated the association between the BDNF Val66Met polymorphism and the performance on tests measuring executive functions in a sample of patients with OCD. A total of 100 patients diagnosed with OCD according to DSM-IV criteria and 110 control subjects were included in this study. Single nucleotide polymorphism (G/A) leading to Val to Met substitution at codon 66 in BDNF was screened in the DNA samples of all participants. The genotype frequencies of BDNF Val66Met polymorphism were compared in OCD patients and healthy controls. The four subgroups of OCD and healthy control subjects, determined according to being Val homozygous or carrying a Met allele, were also compared according to their performance in a battery of neuropsychological tests of executive functions and verbal memory. There was no significant difference for the allele and genotype distributions of BDNF Val66Met polymorphism between the OCD and healthy control groups. Compared to the other three subgroups, OCD-Met carriers were slower on Trail-Making Test part A (TMT A), part B (TMT B) score and its speed-corrected score (TMT B-A). OCD-Met carriers had also poor performance on verbal fluency tasks and several CVLT measures compared only to the healthy control-Met carriers. These results demonstrate that the BDNF Val66Met polymorphism does not appear to be a risk factor for OCD. However, the presence of a BDNF Met allele, which is a known attenuator of BDNF activity, may be associated with a poorer executive functioning in OCD.

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder

In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF) and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF) genotype frequency and other Wisconsin Card Sorting Test domains. Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.

P.7.03 Brain-derived neurotrophic factor gene val66met polymorphism, smoking and suicide-related thoughts in adolescents

P.7.03 Brain-derived neurotrophic factor gene val66met polymorphism, smoking and suicide-related thoughts in adolescents

No association between the brain-derived neurotrophic factor gene Val66Met polymorphism and tardive dyskinesia in schizophrenic patients

Objective This study investigated whether the brain-derived neurotrophic factor ( BDNF) gene Val66Met single-nucleotide polymorphism (SNP) is associated with antipsychotic-induced tardive dyskinesia (TD) in schizophrenia. Methods Genotyping was performed for the BDNF gene Val66Met SNP in Korean schizophrenic patients with ( n = 83) and without TD ( n = 126) who were matched for antipsychotic drug exposure and other relevant variables. Results The frequencies of genotypes ( χ 2 = 2.37, p = 0.306) and alleles ( χ 2 = 0.03, p = 0.867) did not differ significantly between these two groups. Conclusion These findings suggest that the BDNF polymorphism does not play a major role in the susceptibility to TD in schizophrenic patients.

P.2.h.005 Brain-derived neurotrophic factor gene val66met polymorphism and the association between stroke and depression

P.2.h.005 Brain-derived neurotrophic factor gene val66met polymorphism and the association between stroke and depression

No association between the brain‐derived neurotrophic factor gene Val66Met polymorphism and post‐traumatic stress disorder

AbstractPost‐traumatic stress disorder (PTSD) is a chronic anxiety disorder that follows exposure to traumatic events. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary but not sufficient factor. Recent studies have demonstrated that the brain‐derived neurotrophic factor (BDNF) is related to stress‐related psychiatric conditions. In this study, therefore, the genotype and allele frequencies of the BDNF gene Val66Met polymorphism were analyzed in 106 PTSD patients and 161 unrelated healthy controls using a case‐control design. The genotype and allele frequencies for the BDNF gene polymorphism did not differ between the two groups. These findings suggest that the BDNF polymorphism investigated herein does not play a major role in the susceptibility to PTSD at least in the Korean population. Further studies designed to explore the relationship between genetic variations of BDNF and the incidence of PTSD in a larger population may be warranted. Copyright © 2006 John Wiley & Sons, Ltd.