The Role of Brain-Derived Neurotrophic Factor in the Pathophysiology of Psychiatric and Neurological Disorders

Brain-derived neurotrophic factor (BDNF) is a neurotrophin highly expressed in the brain with a potent influence on several aspects of neuronal function. Since its discovery in the early 1980s, BDNF has prompted a great interest in better understanding its physiological role and has been established as the main central neurotrophic factor. BDNF is initially synthesized as a precursor, pro-BDNF, which is then cleaved to form mature BDNF (m-BDNF). A regulated balance between pro-BDNF and m-BDNF is crucial for physiological as well as pathological conditions. The diverse effects of BDNF are mediated through the p75 NT receptor (p75NTR), which binds to its precursor form, and the tropomyosin receptor kinase B (TrkB), which binds to its mature form. Activation of TrkB and p75NTR may produce opposite outcomes in that TrkB receptors have a well-defined trophic role and their activation is proposed to mediate neuronal survival, whereas p75NTR may promote apoptosis. BDNF is highly expressed in limbic structures and cerebral cortex, making it a crucial factor in the regulation of learning and memory, affective behaviors and reward processes. Abnormal BDNF signaling has been proposed to have a crucial role in the course and development of numerous psychiatric and neurological disorders. Moreover, psychotropic drugs used to treat some of these conditions are known to activate BDNF signaling. The present review gives an overview of the involvement of BDNF in the pathology of psychiatric and neurological disorders, compiling what is known from human and animal studies.