Letter to the Editor
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Sep 19, 2022; 12(9): 1264-1267
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1264
Why do we not reverse the path? Stress can cause depression, reduction of brain-derived neurotrophic factor and increased inflammation
Angelo Emilio Claro, Clelia Palanza, Marianna Mazza, Alessandro Rizzi, Linda Tartaglione, Giuseppe Marano, Giovanna Muti-Schuenemann, Marta Rigoni, Paola Muti, Alfredo Pontecorvi, Luigi Janiri, Gabriele Sani, Dario Pitocco
Angelo Emilio Claro, Marianna Mazza, Giuseppe Marano, Luigi Janiri, Gabriele Sani, Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Clelia Palanza, Istituto Italiano di Antropologia, IsiTa, Rome 00185, Italy
Alessandro Rizzi, Linda Tartaglione, Department of Medical and Surgical Sciences, Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Giovanna Muti-Schuenemann, Health Research Methods, Evidence and Impact Department, McMaster University, Ontario K9V 0A0, Canada
Marta Rigoni, Paola Muti, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20126, Italy
Alfredo Pontecorvi, Department of Endocrine-Metabolic and Dermo-Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Dario Pitocco, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Author contributions: Claro AE and Palanza C designed the study and wrote the first draft of the manuscript; Mazza M, Marano G, Rizzi A, Tartaglione L, Muti-Schuenemann G, Rigoni M, Muti P, Pontecorvi A, Janiri L, Sani G and Pitocco D supervised and added important contributions to the paper; All authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marianna Mazza, MD, PhD, Assistant Professor, Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, Rome 00168, Italy. marianna.mazza@policlinicogemelli.it
Received: June 16, 2022
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
Abstract

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.

Keywords: Depression, Inflammation, Brain-derived neurotrophic factor, Type 2 diabetes mellitus, Dementia, Psychological stress

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.