Brain-derived Neurotrophic Factor: a Key Gene Risk Factor and Potential Therapy Target in Bipolar Disorder

Yue Zeng,Juming Li,Yutao Chen,Yuqi Su,T Zhu,A Sharifi,M Anpo

doi:10.1051/e3sconf/202127103069

Abstract

Bipolar Disorder (BD) is a worldwide, multifactorial mental disorder characterized by manic and depressive symptoms of varying degrees. Among all the genetic risk factors correlated with BD, brain-derived neurotrophic factor (BDNF) has emerged as a crucial neutropin that influences BD susceptibility with strong conservative across species and multiple downstream signaling pathways. However, the mechanisms of how BDNF polymorphism can contribute to BD are not yet lucid and systematically reviewed. BDNF Val66Met variant is capable of inducing neurodegenisis and Long-term Depression (LTD), both of which account for pathogenesis in BD. The Val66Met variant is associated with rapid cycling episodes in BD. Another variant, Arg125Met is a potential BD risk variant which elicits neuronal apoptosis by affecting the maturation of BDNF. In this paper, we briefly summarized BD epidemiology, symptoms, BDNF structure, and its action of function. We reviewed various mechanisms of BDNF Val66Met and Arg125Met variant for BD pathogenesis in detail and provided insights into possible BD clinical treatment targets. BDNF has been proven to be a noteworthy gene factor in BD and gene therapy targeted on BDNF is a promising therapeutic strategy that requires further research.

Highlights

Bipolar disorder (BD) is a multifactorial disease associated with severe neuropsychological defects, emotional disorders, and even immune and physiological changes [1]
Changes in neurotrophin levels in particular, such as glial cell derived neurotrophie factor (GDNF), brain-derived neurotrophic factor (BDNF), serum neurotrophin-3 and neurotrophin-4 were observed in the central nervous system (CNS) of BD patients [4, 5]
Among all these risk factors, BDNF is noteworthy. It has been confirmed in genetic studies that the diversity of its gene coding is related to BD, and BDNF Val66Met Polymorphism has been found to have geneenvironment interaction with childhood trauma, which can induce BD to certain extent

Summary

Introduction

Bipolar disorder (BD) is a multifactorial disease associated with severe neuropsychological defects, emotional disorders, and even immune and physiological changes [1]. Among different BDNF variants, the Val66Met SNP (rs6265) has been most widely investigated, though its association with the susceptibility of BD is not concrete as various lines of research contradicts each other [12]. Genetic risk factors (such as BDNF, SNPs) are considered to be one of the important influencing factors of BD. Genetic Factors Multiple SNPs BDNF Val66Met Polymorphism CACNA1C mutation COMT mutation. Among all these risk factors, BDNF is noteworthy. It has been confirmed in genetic studies that the diversity of its gene coding is related to BD, and BDNF Val66Met Polymorphism has been found to have geneenvironment interaction with childhood trauma, which can induce BD to certain extent

Pathophysiology

Treatments

Findings

Conclusion