Preclinical models: Status of basic research in depression

Eric J. Nestler, Elizabeth Gould, Husseini Manji

Research output: Contribution to journalReview articlepeer-review

474 Scopus citations


Approximately one half-century ago several classes of medications, discovered by serendipity, were introduced for the treatment of depression and bipolar disorder. These highly effective medications revolutionized our approach to mood disorders and helped launch the modern era of psychiatry. Yet our progress since those serendipitous discoveries has been disappointing. We still do not understand with certainty how those medications produce their desired clinical effects. We have not introduced newer medications with fundamentally different mechanisms of action than the older agents. We have not identified the genetic and neurobiological mechanisms underlying depression and mania, nor do we understand the mechanisms by which nongenetic factors influence these disorders. We have only a rudimentary understanding of the circuits in the brain responsible for the normal regulation of mood and affect, and of those circuits that function abnormally in mood disorders. In approaching these gaps in our knowledge, this workgroup highlighted four major areas for future investment. These include developing better animal models of mood disorders; identifying genetic determinants of normal and abnormal mood in humans and animals; discovering novel targets and biomarkers of mood disorders and treatments; and increasing the recruitment of investigators from diverse backgrounds to mood disorders research.

Original languageEnglish (US)
Pages (from-to)503-528
Number of pages26
JournalBiological Psychiatry
Issue number6
StatePublished - Sep 15 2002

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry


  • Animal models
  • Biomarkers
  • Bipolar disorder
  • Depression
  • Genetic basis of behavior
  • Mania


Dive into the research topics of 'Preclinical models: Status of basic research in depression'. Together they form a unique fingerprint.

Cite this