[Frontiers in Bioscience S1, 275-295, June 1, 2009]]

Neurochemical and behavioral responses to inflammatory immune stressors

Julie Gibb, Marie-Claude Audet, Shawn Hayley, Hymie Anisman

Institute of Neurosciences, Carleton University, Ottawa, Ontario


1. Abstract
2. Introduction
3. Cytokine influences on the central nervous system
3.1. Cytokines within the brain
3.2. Neurochemical effects of cytokines
3.3. Synergies associated with cytokine treatments
3.4. Sensitization of cytokine-provoked neuronal processes
4. Behavioral Effects Associated With Cytokines - Animal Studies
4.1. Sickness Behaviors
4.2. Depressive-like features elicited in response to pro-inflammatory factors
4.3. Processes governing cytokine-induced behavioral variations
5. Inflammatory factors associated with depression in humans
5.1. Cytokine and acute phase protein correlates in patients with depressive disorders
5.2. Depressive symptoms in relation to allergies, chronic inflammatory diseases and cancer
5.3. Depressive disorder induced by IFN-alpha activation
5.4.Cognitive disturbances associated with cytokine (IFN) immunotherapy
6. Inflammatory processes in relation to neuropsychiatric manifestations in pathological conditions other than depression
6.1. Confusional states and cognitive disturbances in relation to acute inflammation and surgical insult
6.2. Inflammation and cognitive decline in non-demented elderly and in demented patients
6.3. Immune activation and neuropsychiatric symptoms in schizophrenia
7. Summary and perspective
8. Acknowledgment
9. References


Activation of the inflammatory immune system has been associated with the development of psychological disorders such as major depressive disorder (MDD). In this regard, the release of pro-inflammatory cytokines (signaling molecules of the immune system) provokes a constellation of neurochemical and behavioral alterations, reminiscent of the effects of traditional stressors, which if sustained could influence psychological functioning. In animal models, exogenously administered cytokines, as well as bacterial endotoxins and viral analogues, induce a variety of behavioral disturbances collectively known as sickness behavior. Although it is difficult to differentiate the general malaise of sickness engendered by cytokines from the depressogenic effects, clinical studies have revealed increased levels of circulating cytokines and acute phase proteins in patients diagnosed with MDD. Furthermore, the incidence of MDD is increased in patients suffering from chronic inflammatory conditions, and immunotherapy used to treat chronic illnesses such as Hepatitis C was related to high levels of depression that could be attenuated by antidepressant treatment. Together, these findings indicate that activation of the inflammatory immune system may favor the evolution of psychological disturbances.