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Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

Michael Maes1*, Michael Berk2345, Lisa Goehler6, Cai Song78, George Anderson9, Piotr Gałecki10 and Brian Leonard11

Author Affiliations

1 Maes Clinics @ TRIA, Piyavate Hospital, 998 Rimklongsamsen Road, Bangkok 10310, Thailand

2 School of Medicine, Deakin University, Kitchener House, Ryrie Street, Geelong, Victoria, 3220, Australia

3 Orygen Youth Health Research Centre, Centre for Youth Mental Health, 35 Poplar Road, Parkville Victoria, 3052 Parkville, Australia

4 The Mental Health Research Institute of Victoria, Australia Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, 3052, Australia

5 Department of Psychiatry, Melbourne University, Level 1, North Block Main Building Royal Melbourne Hospital, Parkville Victoria, 3050, Australia

6 Center for the Study of Complementary and Alternative Therapies, School of Nursing, University of Virginia, PO Box 800793, Charlottesville, VA 22908, USA

7 Department of Psychology and Neurosciences, Dalhousie University, 1355 Oxford Streeet, Halifax B3H 4R2, Canada

8 Department 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

9 CRC, Rm 30, 57 Laurel street, Glasgow G11 7QT, Scotland, UK

10 Department of Adult Psychiatry, Medical University of Łóź, Aleksandrowska 159, Łóź, 91-229, Poland

11 Department of Pharmacology, Galway University, University Road, Galway, Co.Galway, Ireland

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BMC Medicine 2012, 10:66  doi:10.1186/1741-7015-10-66

Published: 29 June 2012


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.

depression; sickness behavior; inflammation; oxidative stress; cytokines