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BMC Med. 2012; 10: 66.
Published online Jun 29, 2012. doi:  10.1186/1741-7015-10-66
PMCID: PMC3391987
Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways
Michael Maes,corresponding author1 Michael Berk,2,3,4,5 Lisa Goehler,6 Cai Song,7,8 George Anderson,9 Piotr Gałecki,10 and Brian Leonard11
1Maes Clinics @ TRIA, Piyavate Hospital, 998 Rimklongsamsen Road, Bangkok 10310, Thailand
2School of Medicine, Deakin University, Kitchener House, Ryrie Street, Geelong, Victoria, 3220, Australia
3Orygen Youth Health Research Centre, Centre for Youth Mental Health, 35 Poplar Road, Parkville Victoria, 3052 Parkville, Australia
4The Mental Health Research Institute of Victoria, Australia Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, 3052, Australia
5Department of Psychiatry, Melbourne University, Level 1, North Block Main Building Royal Melbourne Hospital, Parkville Victoria, 3050, Australia
6Center for the Study of Complementary and Alternative Therapies, School of Nursing, University of Virginia, PO Box 800793, Charlottesville, VA 22908, USA
7Department of Psychology and Neurosciences, Dalhousie University, 1355 Oxford Streeet, Halifax B3H 4R2, Canada
8Department of Pharmacology, Chinese Academy Engineering Instit ute for the Development of Endangered Medicinal Resources in Southwest China 189 Changgang Road, Xing Ning District, Nanning, Guangxi Post Code 30023, P. R. China
9CRC, Rm 30, 57 Laurel street, Glasgow G11 7QT, Scotland, UK
10Department of Adult Psychiatry, Medical University of Łóź, Aleksandrowska 159, Łóź, 91-229, Poland
11Department of Pharmacology, Galway University, University Road, Galway, Co.Galway, Ireland
corresponding authorCorresponding author.
Michael Maes: dr.michaelmaes/at/hotmail.com; Michael Berk: MIKEBE/at/BarwonHealth.org.au; Lisa Goehler: goehler/at/virginia.edu; Cai Song: cai.song2011/at/gmail.com; George Anderson: anderson.george/at/rocketmail.com; Piotr Gałecki: galeckipiotr/at/wp.pl; Brian Leonard: brian/at/psycholeonard.com
Received April 23, 2012; Accepted June 29, 2012.
Abstract
It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers.
Keywords: depression, sickness behavior, inflammation, oxidative stress, cytokines
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