Elevated immune-inflammatory signaling in mood disorders: a new therapeutic target?

Abstract

Converging translational evidence has implicated elevated immune-inflammatory signaling activity in the pathoetiology of mood disorders, including major depressive disorder and bipolar disorder. This is supported in part by cross-sectional evidence for increased levels of proinflammatory eicosanoids, cytokines and acute-phase proteins during mood episodes, and prospective longitudinal evidence for the emergence of mood symptoms in response to chronic immune-inflammatory activation. In addition, mood-stabilizer and atypical antipsychotic medications downregulate initial components of the immune-inflammatory signaling pathway, and adjunctive treatment with anti-inflammatory agents augment the therapeutic efficacy of antidepressant, mood stabilizer and atypical antipsychotic medications. Potential pathogenic mechanisms linked with elevated immune-inflammatory signaling include perturbations in central serotonin neurotransmission and progressive white matter pathology. Both heritable genetic factors and environmental factors including dietary fatty-acid composition may act in concert to sustain elevated immune-inflammatory signaling. Collectively, these data suggest that elevated immune-inflammatory signaling is a mechanism that is relevant to the pathoetiology of mood disorders, and may therefore represent a new therapeutic target for the development of more effective treatments.

Keywords::

• arachidonic acid
• bipolar disorder
• C-reactive protein
• coronary heart disease
• cytokines
• immunology
• inflammation
• major depressive disorder
• omega-3 fatty acids
• prostaglandins
• serotonin

Financial & competing interests disclosure

This work was supported in part by NIH grants MH083924 and AG03617, and a NARSAD Independent Investigator Award to RK McNamara and MH090250 to FE Lotrich. RK McNamara has received research support from Martek Biosciences Inc., Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca and Eli Lilly, and is a member of the Inflammation Research Foundation scientific advisory board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.