Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1264
Peer-review started: June 16, 2022
First decision: July 13, 2022
Revised: July 20, 2022
Accepted: August 16, 2022
Article in press: August 16, 2022
Published online: September 19, 2022
Processing time: 95 Days and 14.7 Hours
The aim of this paper is to describe the direction of the link between stress, depression, increased inflammation and brain-derived neurotrophic factor (BDNF) reduction. We hypothesize that severe stress or prolonged stress can be the driving factor that promote the onset of depression. Both stress and depression, if not resolved over time, activate the production of transcription factors that will switch on pro-inflammatory genes and translate them into cytokines. This cascade fosters systemic chronic inflammation and reduced plasma BDNF levels. Since people with depression have a 60% increased risk of developing type 2 diabetes (T2D) and show high levels of inflammation and low levels of BDNF, we hypothesize possible reasons that might explain why T2D, depression and dementia are often associated in the same patient.
Core Tip: This paper proposes a distinct interpretation of the link that exists between increased inflammation and reduction of brain-derived neurotrophic factor (BDNF). We describe why most of the people with altered inflammatory status and low BDNF do not automatically have depression, and why some people become depressed without diverging from average serum levels of these markers. We also suggest a reason why the use of tumor necrosis factor-α inhibition has no effect as a therapy in patients with resistant depression and high inflammatory levels.