title: Role of immune-inflammatory and oxidative and nitrosative stress pathways in the etiology of depression: therapeutic implications.
abstract: Accumulating data have led to a re-conceptualization of depression that emphasizes the role of immune-inflammatory processes, coupled to oxidative and nitrosative stress (O&NS). These in turn drive the production of neuroregulatory tryptophan catabolites (TRYCATs), driving tryptophan away from serotonin, melatonin, and N-acetylserotonin production, and contributing to central dysregulation. This revised perspective better encompasses the diverse range of biological changes occurring in depression and in doing so provides novel and readily attainable treatment targets, as well as potential screening investigations prior to treatment initiation. We briefly review the role that immune-inflammatory, O&NS, and TRYCAT pathways play in the etiology, course, and treatment of depression. We then discuss the pharmacological treatment implications arising from this, including the potentiation of currently available antidepressants by the adjunctive use of immune- and O&NS-targeted therapies. The use of such a frame of reference and the treatment benefits attained are likely to have wider implications and utility for depression-associated conditions, including the neuroinflammatory and (neuro)degenerative disorders.
authors.affiliation: CRC, Rm 30, 57 Laurel Street, Glasgow, G11 7QT, Scotland.
authors.forename: George
authors.initials: G
authors.lastname: Anderson
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Olivia
authors.initials: O
authors.lastname: Dean
authors.forename: Steven
authors.initials: S
authors.lastname: Moylan
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003863:Depression / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress; D014364:Tryptophan / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D014364:Tryptophan