Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia

Elaine Walker*, Vijay Mittal, Kevin Tessner

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

392 Scopus citations


Diathesis-stress models of schizophrenia and other psychotic disorders have dominated theorizing about etiology for over three decades. More recently, with advances in our understanding of the biological processes mediating the effects of stress, these models have incorporated mechanisms to account for the adverse impact of stress on brain function. This review examines recent scientific findings on the role of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary neural systems triggered by stress exposure, in the expression of vulnerability for schizophrenia. The results indicate that psychotic disorders are associated with elevated baseline and challenge-induced HPA activity, that antipsychotic medications reduce HPA activation, and that agents that augment stress hormone (cortisol) release exacerbate psychotic symptoms. The cumulative findings are discussed in light of a neural diathesis-stress model that postdates that cortisol has the potential to increase activity of dopamine pathways that have been implicated in schizophrenia and other psychotic disorders.

Original languageEnglish (US)
Pages (from-to)189-216
Number of pages28
JournalAnnual Review of Clinical Psychology
StatePublished - Jan 1 2008


  • Cortisol
  • Dopamine
  • Hippocampus
  • Schizophrenia
  • Stress

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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