Intermediate phenotypes in schizophrenia: A selective review

Gilbert A. Preston, Daniel R. Weinberger

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Studies aiming to identify susceptibility genes for schizophrenia and other complex psychiatric disorders are faced with the confounds of subjective clinical criteria, commonly occurring phenocopies, significant between-subject variability of candidate traits, and the likelihood of allelic and locus heterogeneity that has been shown to define the genetics of other complex human brain and somatic disorders. Additionally, research aimed at identification of the molecular origins of schizophrenia must also deal with the confounding nature of the human brain. Unlike organs with a few common cellular phenotypes, transcriptomes, and proteomes, individual neurons are often distinct from one another in all of these respects. In this review, we present recent work testing the assumption that studies of genetic susceptibility in complex polygenic disorders such as schizophrenia might be enhanced by the identification of intermediate phenotypes related to more fundamental aspects of brain development and function. Progress in the identification of meaningful intermediate phenotypes in schizophrenia has been made possible by the advent of newer methods in cognitive neuroscience and neuroimaging, and the use of combined multimodal techniques.

Original languageEnglish (US)
Pages (from-to)165-179
Number of pages15
JournalDialogues in Clinical Neuroscience
Issue number2
StatePublished - Jul 21 2005
Externally publishedYes


  • Cognition
  • Electrophysiology
  • Genetics
  • Morphometry
  • Neuroimaging
  • Neuropsychology
  • Phenotype
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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