The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders

Christine Heim, Charles Nemeroff

Research output: Contribution to journalArticle

385 Citations (Scopus)

Abstract

The relative contribution of genetic and environmental factors to the development of the major psychiatric disorders has long been debated. Recently, considerable attention has been given to the observations that adverse experiences early in life predispose individuals to the development of affective and anxiety disorders in adulthood. Corticotropin-releasing factor (CRF) is the central coordinator of the endocrinologic, autonomic, immunologic, and behavioral stress responses. When centrally administered, CRF produces many physiologic and behavioral changes reminiscent of both acute stress and depression. Moreover, CRF has also been implicated in the pathogenesis of a variety of anxiety disorders, mainly through CRF neurocircuits connecting the amygdala and the locus ceruleus. Clinical studies have provided convincing evidence for central CRF hypersecretion in depression, and, to a lesser extent, in some anxiety disorders. Evidence mainly from preclinical studies suggests that stress early in life results in persistent central CRF hyperactivity and increased stress reactivity in adulthood. Thus, genetic disposition coupled with early stress in critical phases of development may result in a phenotype that is neurobiologically vulnerable to stress and may lower an individual's threshold for developing depression and anxiety upon further stress exposure. This pathophysiologic model may provide novel approaches to the prevention and treatment of psychopathology associated with stress early in life. Copyright (C) 1999 Society of Biological Psychiatry.

Original languageEnglish
Pages (from-to)1509-1522
Number of pages14
JournalBiological Psychiatry
Volume46
Issue number11
DOIs
StatePublished - Dec 1 1999
Externally publishedYes

Fingerprint

Corticotropin-Releasing Hormone
Anxiety Disorders
Mood Disorders
Brain
Depression
Locus Coeruleus
Amygdala
Psychopathology
Psychiatry
Anxiety
Phenotype

Keywords

  • Anxiety
  • Corticotropin-releasing factor
  • Depression
  • Development
  • Stress

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. / Heim, Christine; Nemeroff, Charles.

In: Biological Psychiatry, Vol. 46, No. 11, 01.12.1999, p. 1509-1522.

Research output: Contribution to journalArticle

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