Strong evidence suggests that liability to schizophrenia is highly heritable. At the same time only a portion of the individuals with a genetic liability develop schizophrenia, which increases the difficulty of isolating relevant genes. The studies proposed in this application apply the tools and constructs of cognitive neuroscience to test the hypothesis that a specific impairment in context processing, a cognitive function related to the control of attention and working memory and associated with the function of dorsolateral prefrontal cortex (DLPFC), may reflect a valid and reliable endophenotype for genetic liability to schizophrenia. First, we will develop a second generation of context processing measures that is both sensitive to the subtle impairments in the healthy relatives of schizophrenia patients, while at the same time interpretable as a specific deficit associated with context processing. Second, the study will test the specificity of context processing impairments to schizophrenia and schizoaffective disorder by comparing schizophrenia and schizoaffective (bipolar type) patients with bipolar patients and controls. Finally, we will study brain activity associated with context processing impairments in the relatives of schizophrenia patients using IMRI. Previous work has found that context processing impairments in schizophrenia patients have been associated with DLPFC dysfunction. We hypothesize that a DLPFC dysfunction associated with specific impairments in context processing will be evident in patients' unaffected relatives. The work proposed in this application has the potential to have important implications for developing behavioral genetic tools to isolate the genes that cause schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH066629-06
Application #
7324829
Study Section
Brain Disorders and Clinical Neuroscience 5 (BDCN)
Program Officer
Breiling, James P
Project Start
2003-12-01
Project End
2009-05-30
Budget Start
2007-12-01
Budget End
2009-05-30
Support Year
6
Fiscal Year
2008
Total Cost
$251,372
Indirect Cost
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Poppe, Andrew B; Carter, Cameron S; Minzenberg, Michael J et al. (2015) Task-based functional connectivity as an indicator of genetic liability to schizophrenia. Schizophr Res 162:118-23
Kang, Seung Suk; MacDonald 3rd, Angus W (2010) Limitations of true score variance to measure discriminating power: psychometric simulation study. J Abnorm Psychol 119:300-6
Jones, Jessica A H; Sponheim, Scott R; MacDonald 3rd, Angus W (2010) The dot pattern expectancy task: reliability and replication of deficits in schizophrenia. Psychol Assess 22:131-41
Wendelken, Carter; Ditterich, Jochen; Bunge, Silvia A et al. (2009) Stimulus and response conflict processing during perceptual decision making. Cogn Affect Behav Neurosci 9:434-47
Goghari, Vina M; MacDonald 3rd, Angus W (2009) The neural basis of cognitive control: response selection and inhibition. Brain Cogn 71:72-83
Yoon, Jong H; Minzenberg, Michael J; Ursu, Stefan et al. (2008) Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. Am J Psychiatry 165:1006-14
van Veen, Vincent; Krug, Marie K; Carter, Cameron S (2008) The neural and computational basis of controlled speed-accuracy tradeoff during task performance. J Cogn Neurosci 20:1952-65
Barch, Deanna M; Carter, Cameron S; CNTRICS Executive Committee (2008) Measurement issues in the use of cognitive neuroscience tasks in drug development for impaired cognition in schizophrenia: a report of the second consensus building conference of the CNTRICS initiative. Schizophr Bull 34:613-8
Becker, Theresa M; Kerns, John G; Macdonald 3rd, Angus W et al. (2008) Prefrontal dysfunction in first-degree relatives of schizophrenia patients during a Stroop task. Neuropsychopharmacology 33:2619-25
Minzenberg, Michael J; Carter, Cameron S (2008) Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology 33:1477-502

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