title: 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.
authors.affiliation: Department of Psychiatry, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA. robert.mcnamara@uc.edu
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood; D004357:Drug Synergism; D019317:Evidence-Based Medicine; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D019964:Mood Disorders / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014150:Antipsychotic Agents; D016207:Cytokines; D007166:Immunosuppressive Agents