Neuroimmunology of depression

Adv Pharmacol. 2021:91:259-292. doi: 10.1016/bs.apha.2021.03.004. Epub 2021 Apr 26.

Abstract

Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Disorder (MDD) is associated with a variety of chronic physical inflammatory and autoimmune disorders, and mood disorders may act synergistically with other medical disorders to worsen patient outcomes. Here, we outline the neuroimmune complement, explore the evidence for altered immune system function in MDD, and present some of the potential mechanisms by which immune cells and molecules may drive the onset and course of MDD. These include pro-inflammatory signaling, alterations in the hypothalamic-pituitary-adrenal axis, dysregulation of the serotonergic and noradrenergic neurotransmitter systems, neuroinflammation, and meningeal immune dysfunction. Finally, we discuss the interactions between current antidepressants and the immune system and propose the possibility of immunomodulatory drugs as potential novel antidepressant treatments.

Keywords: Antidepressants; Brain; Depression; HPA axis; Meninges; Neuroimmunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Depressive Disorder, Major* / drug therapy
  • Humans
  • Hypothalamo-Hypophyseal System
  • Pituitary-Adrenal System

Substances

  • Antidepressive Agents