Dev Proj 4: Identifying IFN-alpha-Induced Microglial Activation Using...

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Behavioral co-morbidities including depression, anxiety, irritability, sleep disturbances, fatigue and impaired cognition in patients with cancer are a serious problem. Studies have shown that the majority of cancer patients will experience one or more of these symptoms during treatment, with over a third or more of patients experiencing persisting symptoms after cancer treatment (Ahles et al 2002, Patrick et al 2003, Williams and Dale 2006). Unfortunately, however, more often than not, these symptoms go unrecognized and untreated, and are frequently considered necessary evils of having cancer or having undergone cancer therapy. The lack of appreciation of behavioral comorbidities in cancer patients can come at a high price. Indeed, a number of studies have documented that cancer patients with behavioral problems exhibit poor adherence to treatment, reduced quality of life, and in several instances, increased morbidity and mortality (Dantzer et al 2001, Hopwood and Stephens 2000, Raison and Miller 2003, Stommel et al 2002). Many reasons are given for the paucity of data regarding the nature and treatment of behavioral problems in cancer patients. However, much of the focus to date has been on the psychological and social/occupational impact of carrying a diagnosis of cancer, which makes it "understandable" why someone with cancer might be emotionally distraught. Nevertheless, exciting new developments regarding communication pathways between the immune system and the brain have revolutionized our understanding of how and why patients may develop behavioral problems during cancer and its treatment (Capuron and Miller 2004, Raison et al 2006). There is increasing appreciation that activation of innate immune inflammatory processes and the release of relevant inflammatory cytokines can significantly influence brain function. Indeed, innate immune cytokines can access the brain and have profound effects on neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior. It remains unclear however, whether cytokines released in the periphery influence brain processes through indirect effects on peripheral nervous system pathways or whether peripheral cytokines activate relevant cell types in the brain including microglia, which in turn become an enduring site of inflammation in the central nervous system.