TY - JOUR
T1 - Sickness Behaviour and Depression
T2 - An Updated Model of Peripheral-Central Immunity Interactions
AU - Turkheimer, Federico E
AU - Veronese, Mattia
AU - Mondelli, Valeria
AU - Cash, Diana
AU - Pariante, Carmine M
N1 - Funding Information:
F Turkheimer has received funding from GlaxoSmithKline for research unrelated to this work. CM Pariante declares a research grant from Janssen and consultation and speakers’ fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and Värde Partners. V Mondelli has received research funding from Johnson & Johnson, a pharmaceutical company interested in the development of anti-inflammatory strategies for depression, but the research described in this paper is unrelated to this funding. D Cash is partially funded by Jazz Pharmaceuticals, Syndesi Therapeutics, Unity Biotechnology and GlaxoSmithKline, but the views expressed in the paper are unrelated to this funding. M Veronese has no disclosures.
Funding Information:
CM Pariante is supported by a Senior Investigator award from the NIHR. FE Turkheimer, M Veronese and V Mondelli are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. V Mondelli is also supported by MQ Brighter Futures grant [MQBF/1 IDEA]. Results leading to the model proposed in this paper were obtained by the BIODEP and FLAME studies. The BIODEP study was funded by a strategic award from the Wellcome Trust (104025) in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer. The FLAME study was supported by Janssen Pharmaceutical Companies of Johnson & Johnson as well as from the NIHR-BRC.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/7
Y1 - 2023/7
N2 - Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain function. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy to improve treatment efficacy, particularly in subjects that do not respond to standard medication. Such new practice requires biomarkers to tailor these new therapies to those most likely to benefit but also validated mechanisms of action describing the interaction between peripheral immunity and brain function to optimize target intervention. These mechanisms are generally studied in preclinical models that try to recapitulate the human disease, MDD, through peripherally induced sickness behaviour. In this proposal paper, after an appraisal of the data in rodent models and their adherence to the data in clinical cohorts, we put forward a modified model of periphery-brain interactions that goes beyond the currently established view of microglia cells as the drivers of depression. Instead, we suggest that, for most patients with mild levels of peripheral inflammation, brain barriers are the primary actors in the pathophysiology of the disease and in treatment resistance. We then highlight data gaps in this proposal and suggest novel lines of research.
AB - Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain function. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy to improve treatment efficacy, particularly in subjects that do not respond to standard medication. Such new practice requires biomarkers to tailor these new therapies to those most likely to benefit but also validated mechanisms of action describing the interaction between peripheral immunity and brain function to optimize target intervention. These mechanisms are generally studied in preclinical models that try to recapitulate the human disease, MDD, through peripherally induced sickness behaviour. In this proposal paper, after an appraisal of the data in rodent models and their adherence to the data in clinical cohorts, we put forward a modified model of periphery-brain interactions that goes beyond the currently established view of microglia cells as the drivers of depression. Instead, we suggest that, for most patients with mild levels of peripheral inflammation, brain barriers are the primary actors in the pathophysiology of the disease and in treatment resistance. We then highlight data gaps in this proposal and suggest novel lines of research.
UR - http://www.scopus.com/inward/record.url?scp=85153228393&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2023.03.031
DO - 10.1016/j.bbi.2023.03.031
M3 - Review article
C2 - 37076054
SN - 0889-1591
VL - 111
SP - 202
EP - 210
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -