Prefrontal cognitive systems in schizophrenia: Towards human genetic brain mechanisms

Hao Yang Tan, Joseph H. Callicott, Daniel R. Weinberger

Research output: Contribution to journalReview articlepeer-review

76 Scopus citations


Schizophrenia has complex genetic heritability. It is also genetically heterogeneous. To the extent that genes are associated with symptom constellations in schizophrenia, they do so by affecting the development and function of neural systems that mediate the expression of such diverse behavioral, cognitive and perceptual phenomena. The genetic mechanisms of human brain dysfunction remain to be well understood. Imaging genetics is an emerging field that attempts to integrate the basic biology of putative disease mechanisms with physiological correlates from the live human brain. Here, we review recent imaging genetics work on prefrontal brain systems associated with working memory and executive function - heritable traits relevant to schizophrenia. Starting with genetic variation in dopaminergic systems (e.g., COMT), we examined the modulation of prefrontal brain networks during active cognitive processing; there is also evidence that variation in the expression of dopamine-related downstream intra-cellular signaling molecules (e.g., AKT1) are implicated. Moreover, these genetic variants evidence epistasis on neuroimaging measures, lending further support to the conceptualization that non-additive combinations of multiple genes modulate active human cognitive brain mechanisms. The imaging genetics platform therefore could extend understanding of genetic mechanisms of human cognitive brain processes relevant to neuropsychiatric disease.

Original languageEnglish (US)
Pages (from-to)277-298
Number of pages22
JournalCognitive Neuropsychiatry
Issue number4-5
StatePublished - Sep 2009
Externally publishedYes


  • Dopamine
  • Genetics
  • MRI
  • Working memory

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Psychiatry and Mental health


Dive into the research topics of 'Prefrontal cognitive systems in schizophrenia: Towards human genetic brain mechanisms'. Together they form a unique fingerprint.

Cite this