title: Pre-treatment effects of peripheral tumors on brain and behavior: neuroinflammatory mechanisms in humans and rodents.
abstract: Cancer patients suffer high levels of affective and cognitive disturbances, which have been attributed to diagnosis-related distress, impairment of quality of life, and side effects of primary treatment. An inflammatory microenvironment is also a feature of the vast majority of solid tumors. However, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and cognitive disturbances. In this review, we summarize the burgeoning evidence from rodent cancer models that solid tumors alter neurobiological pathways and subsequent behavioral processes with relevance to affective and cognitive disturbances reported in human cancer populations. We consider, in parallel, the evidence from human clinical cancer research demonstrating that affective and cognitive disturbances are common in some malignancies prior to diagnosis and treatment. We further consider the underlying neurobiological pathways, including altered neuroinflammation, tryptophan metabolism, prostaglandin synthesis and associated neuroanatomical changes, that are most strongly implicated in the rodent literature and supported by analogous evidence from human cancer populations. We focus on the implications of these findings for behavioral researchers and clinicians, with particular emphasis on methodological issues and areas of future research.
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Schrepf
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, IA 52242, USA; Departments of Urology and Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
authors.affiliation: Institute for Behavioral Medicine Research, Departments of Psychiatry and Behavioral Health and Neuroscience, Ohio State University, Columbus, OH 43210, USA. Electronic address: leah.pyter@osumc.edu.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Pyter
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000209:etiology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D019964:Mood Disorders / Q000209:etiology*; D009369:Neoplasms / Q000150:complications* / Q000503:physiopathology / Q000523:psychology / Q000628:therapy; D051381:Rats
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Cancer; Cognition; Cytokines; Depression