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Open Access Highly Accessed Opinion

So depression is an inflammatory disease, but where does the inflammation come from?

Michael Berk1234*, Lana J Williams12, Felice N Jacka12, Adrienne O’Neil15, Julie A Pasco16, Steven Moylan1, Nicholas B Allen7, Amanda L Stuart1, Amie C Hayley1, Michelle L Byrne7 and Michael Maes18

Author Affiliations

1 IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia

2 Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia

3 Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia

4 Orygen Youth Health Research Centre, Parkville, VIC, Australia

5 School of Public health and Preventive Medicine, Monash University, Melbourne, VIC, Australia

6 NorthWest Academic Centre, Department of Medicine, The University of Melbourne, St Albans, VIC, Australia

7 Melbourne School of Psychological Sciences, University of Melbourne, Parkville, VIC, Australia

8 Department of Psychiatry, Chulalongkorn University, Rama Road, Bangkok, Thailand

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BMC Medicine 2013, 11:200  doi:10.1186/1741-7015-11-200

Published: 12 September 2013



We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’


This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.


The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.

Depression; Inflammation; Cytokines; Diet; Obesity; Exercise; Smoking; Vitamin D; Dental cares; Sleep; Atopic; Gut; Oxidative stress