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

¹ School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
² College of Life Sciences, Northwest A&F University, Xianyang, Shanxi, China.
³ International Department, Zibo Experimental High School, Zibo, Shandong, China.

^* Corresponding author: zengy97@mail2.sysu.edu.cn
^† Those authors contributed equally.

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.