Single nucleotide polymorphism of BDNF Val66Met (rs6265) and its association to neuropsychiatric disorders

Abstract

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the central nervous system and was shown to be involved in neuronal growth, differentiation and synaptic plasticity. A single nucleotide polymorphism at the pro-region of the BDNF gene (rs6265) has been reported to alter the amino acid from valine to methionine at codon 66 and was associated with neuropsychiatric disorders in several studies. To date, the results on the association of BDNF rs6265 to the aetiology of the neuropsychiatric illnesses have been inconsistent with some studies reporting a positive association and others reporting no association. Concerning the past inconsistent reports, this mini-review aims at determining the association of BDNF rs6265 and neuropsychiatric disorders among the different studies. Firstly, we discuss the findings on studies reporting the association of BDNF rs6265 with depression whereby a positive association between the BDNF variant and depression was obtained in several studies on the Caucasian, German, Chinese, and Malaysian population but not in studies on the Korean and other populations. Likewise, some studies found the occurrence of the SNP to be associated with a reduction in the BDNF level in depressed cases, but others found no effect at all. We then reported findings on the association of BDNF rs6265 with anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, bipolar disorder, and schizophrenia. Val allele has been found associated with these disorders, whereas some studies reported the involvement of the Met allele, and some reported no association at all. Similarly, the association of the BDNF variant with the BDNF level remains controversial. It is, therefore, essential to conduct more studies with larger sample sizes and look at the haplotype level to determine the association.

Neuroprotective effect of Val variant of BDNF Val66Met polymorphism on hippocampus is modulated by the severity of menstrual pain

“…We observed that BDNF Val66Met allele dosage effects were more prominent in the right hippocampus, which may be associated with the hemispheric functional asymmetry of the hippocampus. It has been shown in human studies and animal models ( Chen et al, 2006 , Faris et al, 2020 , Montag et al, 2010 ) that the BDNF Met allele exhibits increased anxiety-related behaviors under stress, which in turn may increase the risk of psychiatric mood disorders, suggestive of gene ( BDNF Val66Met polymorphism) - environment (stress) interactions. Negative stimuli with aversive emotions tend to engage the right hippocampus more (Holt et al, 2005) for emotional processing ( Ahern and Schwartz, 1985 ).…”

BDNF Val66Met Polymorphism: Suggested Genetic Involvement in Some Children with Learning Disorder

“…Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin expressed in the central nervous system and was reported to be involved in neuronal growth and differentiation and synaptic plasticity, especially in the frontostriatal-cerebellar circuits and ventral striatal-limbic circuits (Faris et al 2020). These circuits are critical for the development of memory and visual motor integration abilities.…”

“…This polymorphism leads to deficient translocation and activity-dependent secretion of mature BDNF (Tsai 2018). It has been linked to impaired cognitive functioning in healthy adults and to several clinical features of many neuropsychiatric disorders such as major depressive disorder, Parkinson's disease, and Alzheimer's disease, in addition to diabetic patients (Bakusic et al 2021;Cagni et al 2017;Faris et al 2020;Miranda et al 2019). Performance of memory was one of the first cognitive domains to be extensively investigated for the influence of Val66Met polymorphism.…”