Depression in Narcolepsy

Abstract

Major Depressive Disorder (MDD) is thought to develop from a complex combination of environmental stressors superimposed on to a vulnerable neural substrate. Many diseases increase the risk of developing MDD, either from the psychosocial stress of the illness or because the illness causes direct dysfunction of the nervous system. Narcolepsy is one such illness in which the disease can cause both significant life stress and direct neuronal dysregulation. In the past decade significant advances have been made in understanding the neuronal basis of narcolepsy since the recognition that loss of orexin neurons (also known as hypocretin neurons) plays an important role in the development of certain forms of the disorder. Mouse models of narcolepsy now allow us to specifically test the role of orexin signaling in the regulation of mood and affect. Reduced levels of orexin peptide have been reported in human patients with MDD and in rodent models of chronic stress further strengthening the connection between orexin and depression. In this chapter, we will review the clinical findings on depression in narcolepsy, discuss the neurobiology of orexin signaling, and speculate on the mechanisms that mediate this association. (PsycInfo Database Record (c) 2020 APA, all rights reserved)