Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression?
BACKGROUND
The endocannabinoid (eCB) system, an endogenous lipid signaling system, appears to be dysregulated in depression. The role of endocannabinoids (eCBs) as potent immunomodulators, together with the accumulating support for a chronic low-grade inflammatory profile in depression, suggests a compelling hypothesis for a fundamental impairment in their intercommunication, in depression.


OBJECTIVE
We aim to review previous literature on individual associations between the immune and eCB systems and depression. It will focus on peripheral and central mechanisms of crosstalk between the eCB and immune systems. A potential dysregulation in this crosstalk will be discussed in the context of depression.


RESULTS
Investigations largely report a hypoactivity of the eCB system and increased inflammatory markers in individuals with depression. Findings depict a multifaceted communication whereby immunocompetent and eCB-related cells can both influence the suppression and enhancement of the other's activity in both the periphery and central nervous system. A dysregulation of the eCB system, as seen in depression, appears to be associated with central and peripheral concentrations of inflammatory agents implicated in the pathophysiology of this illness.


CONCLUSIONS
The eCB and immune systems have been individually associated with and implicated in pathogenic mechanisms of depression. Both systems tightly regulate the other's activity. As such, a dysregulation in this crosstalk has potential to influence the onset and maintenance of this neuropsychiatric illness. However, few studies have investigated both systems and depression conjointly. This review highlights the demand to consider joint eCB-immune interactions in the pathoetiology of depression.
Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Emily
E
Boorman
Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Zuzanna
Z
Zajkowska
Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Rumsha
R
Ahmed
Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Carmine M
CM
Pariante
Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. patricia.zunszain@kcl.ac.uk.
Patricia A
PA
Zunszain
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology*; D063388:Endocannabinoids; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D020239:Receptor Cross-Talk; D043882:Receptors, Cannabinoid
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid
2-AG; Anandamide; CNS; Cytokine; Eicosanoids; Inflammation; Lymphocyte; Microglia; Microglial polarisation; Prostaglandin