title: Neurosteroids, stress and depression: potential therapeutic opportunities.
abstract: Neurosteroids are potent and effective neuromodulators that are synthesized from cholesterol in the brain. These agents and their synthetic derivatives influence the function of multiple signaling pathways including receptors for γ-aminobutyric acid (GABA) and glutamate, the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS). Increasing evidence indicates that dysregulation of neurosteroid production plays a role in the pathophysiology of stress and stress-related psychiatric disorders, including mood and anxiety disorders. In this paper, we review the mechanisms of neurosteroid action in brain with an emphasis on those neurosteroids that potently modulate the function of GABA(A) receptors. We then discuss evidence indicating a role for GABA and neurosteroids in stress and depression, and focus on potential strategies that can be used to manipulate CNS neurosteroid synthesis and function for therapeutic purposes.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. zorumskc@wustl.edu
authors.forename: Charles F
authors.initials: CF
authors.lastname: Zorumski
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Covey
authors.forename: Steven
authors.initials: S
authors.lastname: Mennerick
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D003863:Depression / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000523:psychology*; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid