Abnormalities of eye movement control and spatial cognition are well-established deficits in schizophrenia. However, the regional disturbances in brain function causing these deficits are not yet known. This application proposes a series of integrated behavioral and fMRI studies designed to identify causes of pursuit eye movement and spatial working memory deficits in schizophrenia. We will determine whether there are intrinsic functional disturbances in extrastriate regions that process visual motion information (Area MT) using both optic flow and motion aftereffect paradigms. We will parametrically manipulate attentional enhancements during pursuit tracking to clarify the causes of what appears to be a reduced influence of extra retinal signals on the control of pursuit eye movements in schizophrenia. We will use an oculomotor delayed response (ODR) task to study spatial working memory impairments in schizophrenia. We will parametrically manipulate the rate of """"""""distractor"""""""" information presented during the delay period of this prototypic spatial working memory task in order to model changes in dorsal brain regions of interest across a range of processing load conditions. Fifty schizophrenic patients will be recruited, 25 first episode antipsychotic-naive patients and 25 unmedicated chronic patients. In addition to matched healthy subjects, 50 patients with non-bipolar depression will be recruited as a clinical comparison group. Depressed patients are of interest because our group and others have demonstrated relevant disturbances of eye movement control and spatial cognition in this disorder. Subjects will be restudied after 3 months, during which all patients will receive controlled treatment, in order to assess the extent of normalization of brain function associated with treatment and clinical recovery. The results of these studies will clarify the neurobiological basis of one of the most robust and promising biological markers of risk for schizophrenia, and of working memory disturbances known to be a prominent component of the neuropsychological profile of the disorder. Findings will also clarify the diagnostic specificity of regional brain disturbances causing these abnormalities, and the impact of known effective treatments upon them.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH062134-05
Application #
6652456
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (05))
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
5
Fiscal Year
2003
Total Cost
$350,708
Indirect Cost
Name
University of Illinois at Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Stevenson, J M; Reilly, J L; Harris, M S H et al. (2016) Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes. Transl Psychiatry 6:e739
Keedy, Sarah K; Reilly, James L; Bishop, Jeffrey R et al. (2015) Impact of antipsychotic treatment on attention and motor learning systems in first-episode schizophrenia. Schizophr Bull 41:355-65
Bishop, Jeffrey R; Reilly, James L; Harris, Margret S H et al. (2015) Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophrenia. Psychopharmacology (Berl) 232:145-54
Lencer, Rebekka; Bishop, Jeffrey R; Harris, Margret S H et al. (2014) Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis. Eur Arch Psychiatry Clin Neurosci 264:345-55
Keedy, Sarah K; Bishop, Jeffrey R; Weiden, Peter J et al. (2014) Disease and drug effects on internally-generated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder. Schizophr Res 159:101-6
Daros, Alexander R; Ruocco, Anthony C; Reilly, James L et al. (2014) Facial emotion recognition in first-episode schizophrenia and bipolar disorder with psychosis. Schizophr Res 153:32-7
Rosen, Cherise; Marvin, Robert; Reilly, James L et al. (2012) Phenomenology of first-episode psychosis in schizophrenia, bipolar disorder, and unipolar depression: a comparative analysis. Clin Schizophr Relat Psychoses 6:145-51
Lu, Lisa H; Zhou, Xiaohong Joe; Fitzgerald, Jacklynn et al. (2012) Microstructural abnormalities of white matter differentiate pediatric and adult-onset bipolar disorder. Bipolar Disord 14:597-606
Sweeney, John A (2011) Viewing the elephant from 200 feet: reconstructing the schizophrenia syndrome. Schizophr Res 127:18-9
Lencer, Rebekka; Keedy, Sarah K; Reilly, James L et al. (2011) Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking. Psychiatry Res 194:30-8

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