title: Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.
abstract: Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University , Jupiter, Florida 33458, United States.
authors.forename: Matthew J
authors.identifier: 0000-0002-3277-3062
authors.initials: MJ
authors.lastname: Robson
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University , Jupiter, Florida 33458, United States.|Department of Pharmacology, Vanderbilt University , Nashville, Tennessee 37240-7933, United States.
authors.forename: Meagan A
authors.initials: MA
authors.lastname: Quinlan
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University , Jupiter, Florida 33458, United States.
authors.forename: Randy D
authors.identifier: 0000-0002-2182-6966
authors.initials: RD
authors.lastname: Blakely
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D016207:Cytokines; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
keywords: Serotonin; cytokines; immune system; inflammation; major depressive disorder; serotonin transporter