Dysregulation of Noradrenergic Activity: Its Role in Conceptualizing and Treating Major Depressive Disorder, Schizophrenia, Agitation in Alzheimer's Disease, and Posttraumatic Stress Disorder

Abstract

When discussing neurotransmitters whose signaling plays an important role in psychiatric illnesses, serotonin and dopamine may be the first that come to mind. Although serotonin and dopamine have significant roles, the impact of norepinephrine signaling is often overlooked. A growing body of evidence suggests that hyperactivity of norepinephrine signaling is an underlying issue in psychiatric disorders; conversely, there is evidence to suggest that deficits in the noradrenergic system are just as significant. Hence, alterations in noradrenergic activity are better characterized as dysregulation rather than a reductive, outdated formulation of "too much" or "too little" activity. Therefore, symptoms such as agitation, irritability, hyperarousal, and insomnia could be treated by targeting the underlying pathophysiology related to noradrenergic dysregulation with targeted treatments. In a recent consensus panel meeting, 5 experts reviewed the available evidence of altered noradrenergic activity and its potential role in some of the most common psychiatric disorders. This Academic Highlights article summarizes their discussion and presents the panel's conclusions.