New hypothesis and treatment targets of depression: an integrated view of key findings

Abstract

Major depressive disorder (MDD) is a common and devastating psychiatric disorder characterized by persistent low mood, cognitive disorder, and impaired social function. Despite its complex mechanisms, increasing evidence has identified the involvement of neurotrophic factors, inflammatory cytokines, the hypothalamuspituitary-adrenal axis, and glutamate receptors in the pathophysiology of this illness. The present review synthesizes recent research achievements to defi ne the network between different hypotheses of MDD and to understand which part is most pivotal for its pathogenesis. By integrating MDD-related signal pathways, we highlight brain-derived neurotrophic factor (BDNF) dysfunction and increased apoptosis as the fi nal common cascades, and new therapeutic strategies aiming to enhance BDNF function have been shown to exert a rapid and effective antidepressant action.

No effect of escitalopram versus placebo on brain-derived neurotrophic factor in healthy individuals: a randomised trial

“…A new hypothesis regarding depression was presented by Cai et al (2) in their recent review who state that it is important to have an integrated view of the mechanisms underlying depression. Genetic and stress vulnerabilities interplay to initiate a cascade of neurobiological changes that disrupt a dynamic system.…”

“…Antidepressants seemingly exert their therapeutic action through their ability to increase the synaptic content of monoamine neurotransmitters; however, the effects on neurotrophic factors, especially BDNF, also seem to play a role (2,15). A study recently investigated serum proBDNF/BDNF and response to the selective serotonin re-uptake inhibitor fluvoxamine in unmedicated first-episode patients with depression and found that no association between serum levels of proBDNF and BDNF during the treatment period (16).…”

Neuronal correlates of depression

“…The mechanisms of action of BDNF in the context of depression in these various brain regions are still unclear. The differential interaction of pre- and post-synaptic BNDF-TRKB pathway with various intra and extracellular signaling systems such as second messenger pathways (including phospholipase Cγ, PI3K and MAPK/ERK pathways), inflammatory cytokines, excitatory glutamatergic neurotransmitters and stress hormones could in part result in the contrasting observations of BDNF levels in the different regions of the brains in relation to depression [35]. …”

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

“…Major depression disorder (MDD) is one of the most common debilitating mood disorders worldwide and becoming the second leading disease contributing to the years lived with disability by 2013 (Cai, Huang, & Hao, 2015). The prominent and persistent low mood, mental retardation, cognitive impairment, volitional decline and somatic symptoms companied the patients lifelong and impaired their social functions.…”