The Clinical and Therapeutic Potentials of Dehydroepiandrosterone and Pregnenolone in Schizophrenia

Neuroscience. 2011 Sep 15;191:91-100. doi: 10.1016/j.neuroscience.2011.04.017. Epub 2011 Apr 24.


Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone (PREG), and their sulfates (DHEAS and PREGS) display multiple effects on the central nervous system. Specifically, neurosteroids have various functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. In addition, neurosteroid levels are altered in stress-related neuropsychiatric disorders. This review focuses on the alterations of these neurosteroids in schizophrenia and on their association with clinical and neurocognitive manifestations. As described henceforth, findings from clinical studies have revealed that PREG, DHEA, and their sulfates might be involved in the pathophysiology of schizophrenia, and in some of its manifestations. Clinical trials for the evaluation of these neurosteroids face challenges in terms of experimental design, dosing strategy, data analysis, and interpretation. The review concludes with a list of suggested topics for future research. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / metabolism
  • Dehydroepiandrosterone Sulfate / metabolism
  • Dehydroepiandrosterone Sulfate / therapeutic use
  • Drug Synergism
  • Humans
  • Neurotransmitter Agents / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Schizophrenia / pathology


  • Antipsychotic Agents
  • Neurotransmitter Agents
  • Dehydroepiandrosterone Sulfate