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Selective modulation of neuroimaging intermediate phenotypes by schizophrenia risk genes

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • KE Healy
  • R Rasetti
  • Q Chen
  • X Cheng
  • B Kolachana
  • JH Callicott
  • KF Berman
  • VS Mattay
  • DR Weinberger


An intermediate phenotype related to schizophrenia is a heritable trait located in the pathogenic pathway from genetic predisposition to psychopathology. Several independent neuroimaging intermediate phenotypes appear promising in genetic studies of schizophrenia to identify potential risk genes. These phenotypes include altered BOLD fMRI activation in the prefrontal cortex, hippocampus, and anterior cingulate during working memory, episodic memory, and cognitive control tasks respectively. They current study tests the hypothesis that these phenotypes are selectively modulated by different potential schizophrenia risk genes. Our results indicated that specific polymorphisms in risk genes influence more than one phenotype, a single phenotype, or have no significant effects. Particularly, specific polymorphisms in AKT1 and CACNA1c modulated all three phenotypes, polymorphisms in COMT and DISC1 modulated episodic and working memory phenotypes, and polymorphisms in ERB4 and ZNF804A modulated working memory and response inhibition phenotypes respectively. NRG1 and RELN failed to show significant effects. These preliminary results suggest selective modulation of the different neuroimaging intermediate phenotypes by schizophrenia risk genes, suggesting discrete biological mechanisms of risk in some but not all brain circuits and their related cognitive functions. Further larger studies are needed to ensure the gene effects observed are not due to sample and effect size differences.

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