title: Mapping inflammation onto mood: Inflammatory mediators of anhedonia.
abstract: Evidence supports inflammatory involvement in mood and cognitive symptoms across psychiatric, neurological and medical disorders; however, inflammation is not a sensitive or specific characteristic of these diagnoses. The National Institute of Mental Health Research Domain Criteria (RDoC) ask for a shift away from symptom-based diagnoses toward a transdiagnostic neurobiological focus in the study of brain illnesses. The RDoC matrix may provide a useful framework for integrating the effects of inflammation on brain function. Based on preclinical and clinical findings, relevant relationships span negative and positive valence systems, cognitive systems, systems for social processes and arousal/regulatory systems. As an exemplar, we consider the psychopathological domain of anhedonia, conceptualizing the relevance of inflammation (e.g., cellular immunity) and downstream processes (e.g., indoleamine 2,3-dioxygenase activation and oxidative inactivation of tetrahydrobiopterin) across RDoC units of analysis (e.g., catecholamine neurotransmitter molecules, nucleus accumbens medium spiny neuronal cells, dopaminergic mesolimbic and mesocortical reward circuits, animal paradigms, etc.). We discuss implications across illnesses affecting the brain, including infection, major depressive disorder, stroke, Alzheimer's disease and type 2 diabetes.
authors.affiliation: University of Toronto, Department of Pharmacology & Toxicology, Canada; Sunnybrook Research Institute, Hurvitz Brain Sciences Program, Canada; University Health Network Toronto Rehabilitation Institute, Canada. Electronic address: w.swardfager@utoronto.ca.
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
authors.affiliation: University Health Network Toronto Western Research Institute, Mood Disorders Psychopharmacology Unit, Canada; University of Toronto, Department of Psychiatry, Canada.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rosenblat
authors.affiliation: University of Toronto Mississauga, Institute of Medical Sciences, Canada.
authors.forename: Meriem
authors.initials: M
authors.lastname: Benlamri
authors.affiliation: University of Toronto, Department of Pharmacology & Toxicology, Canada; University Health Network Toronto Western Research Institute, Mood Disorders Psychopharmacology Unit, Canada; University of Toronto, Department of Psychiatry, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D059445:Anhedonia / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans
chemical_list: D016207:Cytokines
keywords: Anhedonia; Cytokine; Depression; Dopamine; Inflammation; Research Domain Criteria; Reward