Neuroendocrine Regulation of Behavior

Heather C. Brenhouse, Andrea Danese, Rodrigo Grassi-Oliveira, Brenhouse, Heather C., Danese, Andrea, Grassi-Oliveira, Rodrigo

Maltreatment and trauma in childhood, termed early-life stress (ELS), has long-term effects on the immune system. ELS impacts immune signaling at the time of exposure but also disrupts the developmental trajectory of certain immunological processes, both in the periphery and in the brain. One consequence of these early alterations is a heightened immune response to stressors later in life. However, chronic and sustained inflammatory response can also lead to excitotoxicity and prevent typical brain development. In this chapter, we discuss current progress toward understanding the contribution of neuroimmune signaling to ELS-attributable dysfunction or maladaptation with a focus on postnatal experiences. To do so we first present an operational definition of ELS. Then, we offer a brief overview of the immune system and neuroimmune development, followed by a section discussing the interaction between immunity, childhood trauma, and mental disorders in humans. We present evidence from animal models about immune alterations after ELS and discuss the ways in which ELS-induced immune changes ultimately affect brain and behavior, as well as the importance of individual differences and future directions in this field. Taken together, we submit that when encountered with ELS, some core brain circuits could develop differently via various mechanisms involving dysfunctional immune reprograming. However, given the remarkable plasticity of both the brain and the immune system, many of the deleterious effects of ELS may be mitigated with interventions that account for sex and target neuroimmune interactions over the lifespan.