Abstract
Despite a historical focus on neurally mediated interoceptive signaling mechanisms, humoral (and even cellular) signals also play an important role in communicating bodily physiological state to the brain. These signaling pathways can perturb neuronal structure, chemistry, and function, leading to discrete changes in behavior. They are also increasingly implicated in the pathophysiology of psychiatric disorders. The importance of these humoral signaling pathways is perhaps most powerfully illustrated in the context of infection and inflammation. Here we provide an overview of how interaction of immune activation of neural and humoral interoceptive mechanisms mediates discrete changes in brain and behavior and highlight how activation of these pathways at specific points in neural development may predispose to psychiatric disorder. As our mechanistic understanding of these interoceptive pathways continues to emerge, it is revealing novel therapeutic targets, potentially heralding an exciting new era of immunotherapies in psychiatry.