炎症が進化の過程で生存に役立ったものの、現代では精神疾患を含む多くの病気の原因となっているというテーマを扱っています。慢性的な炎症が脳機能や行動に影響を与え、抑うつや他の精神疾患を引き起こす可能性があることが解説されています。進化的および生物学的なメカニズムが、精神的健康と免疫系の関係に重要な役割を果たすという視点が提供されています。
Malaise, melancholia and madness: The evolutionary legacy of an inflammatory bias
Author links open overlay panelCharles L. Raison a
, Andrew H. Miller
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This article introduces the Special Issue on Inflammation and Mental Health and emphasizes the evolutionary legacy of an inflammatory bias that underlies the contributions of the immune system to behavioral disorders.
Abstract
Evolutionary imperatives bred a vigorous and highly orchestrated behavioral and immune response to the microbial world that served to promote species survival and propagation. The resultant legacy is an inflammatory bias which goes largely unchecked in the modern world and is provoked not only by pathogens but also now by people. In this commentary, the authors’ contributions to the special issue on Inflammation and Mental Health are described, beginning with the origins of the inflammatory bias, its roots in genetic predispositions to behavioral adaptations and ultimately maladaptations, and its consequences on the developing brain. In addition, the mechanisms by which the immune system engages behavior are described including a central role for the inflammasome which may serve to link psychological stress with inflammatory and behavioral responses. Neurotransmitter systems that mediate effects of the immune system on behavior are also described along with interactions of the inflammatory bias with depression and their convergent impact on the response to stress and medical illness. Finally, translational implications are discussed including data from a clinical trial using a cytokine antagonist in depressed patients, which suggests an interaction of the inflammatory bias with other evolutionary legacies including those related to food consumption and their modern consequences of obesity and the metabolic syndrome. Taken together, the articles offer a sampling of the rich literature that has evolved regarding the role of the immune system in behavioral disorders. The grounding of this relationship in our evolutionary past may serve to inform future research both theoretically and therapeutically.
Introduction
As we have learned more about interactions between the brain and the immune system, it is increasingly apparent that cytokines and other immune molecules and cells play a Janus-faced role in central nervous system (CNS) function. Indeed, immune system molecules and cells are an essential component of numerous processes that are fundamental to the maintenance of neuronal integrity including neurogenesis, synaptic remodeling, and neurotransmission (Yirmiya and Goshen, 2011). For example, inhibition of cytokines through the use of antagonists or gene targeting is associated with significant impairments in learning and memory in conjunction with deficits in the elemental processes that support these functions including long-term potentiation (Yirmiya and Goshen, 2011). Similar results have been found following removal of cellular components of the immune system including T cells and microglia (Kipnis et al., 2004, Sierra et al., 2013, Ziv et al., 2006). Recent data suggest that even the healing effects of antidepressants may be in part dependent upon the induction of an immune response (Warner-Schmidt et al., 2011).
Side-by-side with these sustaining influences of the immune system on neuronal function is the specter of a destructive force driven by an overactive immune response or inflammation that in its attempt to contain and control a perceived assault can wreak havoc on the body and the brain, ultimately affecting behavior (Dantzer et al., 2008, Miller et al., 2009). While the short-term goal to enact protective responses at the cellular and organismic level is essential to survival, in the long run, chronic immune activation and inflammation, comes at a high cost, contributing to the immense personal and economic burden of neuropsychiatric disorders as well as other illnesses in our society. Much attention has appropriately been paid to the mechanisms of the effects of inflammation on the pathways to pathology in mental illnesses. However, it is important to recognize that there is a method to the madness, beginning with the need to survive in a hostile microbial environment in ancestral times, and ultimately resulting in the legacy of an inflammatory bias which when triggered or fostered by environmental conditions can lead to a host of maladies that are overrepresented in the modern world including allergic disorders, cardiovascular disease, diabetes, cancer and neuropsychiatric disorders (Couzin-Frankel, 2010). In this special issue of Brain Behavior Immunity, we will begin with human evolution and through a series of papers will expand upon the basis of the inflammatory bias, its genetic representations, the dire consequences on a developing brain, the mechanisms impacting CNS function, the role of environmental triggers and ultimately translational relevance (Fig. 1).
