The etiopathophysiology of schizophrenia is incompletely understood. Evidence supports an association between genetic liability for schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, and it has been suggested that SPEM can serve as a phenotype in molecular genetic studies. However, the neural basis of reported abnormalities in SPEM is not well understood, and even less is known about how genetic effects are translated into aberrant neural circuit controlling SPEM. Knowledge of the biological mechanisms underlying SPEM abnormalities and their relationship to the schizophrenia phenotype may provide critical insights into the etiology of this disease. The goal of the proposed research is to combine functional magnetic resonance imaging (fMRI) and SPEM measures to study 1) the underlying neural mechanism of schizophrenia-related SPEM impairments; and 2) the degree to which pursuit-related imaging changes aggregate in families. We have behaviorally modeled the relative contributions of retinal motion and extraretinal motion signals to smooth pursuit maintenance in healthy subjects and in relatives of schizophrenia patients. The results indicate that performance in healthy subjects depends primarily on the predictive, or extraretinal motion input, while relatives of schizophrenia patients show deficits in this component of the pursuit response. This deficit may lead to an increased reliance on the immediate, retinal motion sensory input to maintain smooth pursuit. We hypothesize that this pattern of behavioral abnormality has a neurophysiological basis that will be detectable in fMRI imaging signal as reduced activation in the extraretinal motion processing pathway accompanied by a compensatory increase in activation in regions responsible for retinal motion processing. We further hypothesize that this pattern of neural activity will be present in the clinically unaffected siblings of affected probands, supporting a genetic influence on the neural circuit controlling predictive smooth pursuit deficit in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH070644-02
Application #
7012337
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Wynne, Debra K
Project Start
2005-02-01
Project End
2010-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
2
Fiscal Year
2006
Total Cost
$182,304
Indirect Cost
Name
University of Maryland Baltimore
Department
Psychiatry
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Wright, Susan; Kochunov, Peter; Chiappelli, Joshua et al. (2014) Accelerated white matter aging in schizophrenia: role of white matter blood perfusion. Neurobiol Aging 35:2411-2418
Hong, L Elliot; Schroeder, Matthew; Ross, Thomas J et al. (2011) Nicotine enhances but does not normalize visual sustained attention and the associated brain network in schizophrenia. Schizophr Bull 37:416-25
Hong, L Elliot; Summerfelt, Ann; Buchanan, Robert W et al. (2010) Gamma and delta neural oscillations and association with clinical symptoms under subanesthetic ketamine. Neuropsychopharmacology 35:632-40
Zhang, Xiaochu; Stein, Elliot A; Hong, L Elliot (2010) Smoking and schizophrenia independently and additively reduce white matter integrity between striatum and frontal cortex. Biol Psychiatry 68:674-7
Hong, L Elliot; Hodgkinson, Colin A; Yang, Yihong et al. (2010) A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. Proc Natl Acad Sci U S A 107:13509-14
Fowler, Joanna S; Logan, Jean; Azzaro, Albert J et al. (2010) Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157. Neuropsychopharmacology 35:623-31
Hong, L Elliot; Gu, Hong; Yang, Yihong et al. (2009) Association of nicotine addiction and nicotine's actions with separate cingulate cortex functional circuits. Arch Gen Psychiatry 66:431-41
Hong, L Elliot; Turano, Kathleen A; O'Neill, Hugh B et al. (2009) Is motion perception deficit in schizophrenia a consequence of eye-tracking abnormality? Biol Psychiatry 65:1079-85
Wonodi, Ikwunga; Hong, L Elliot; Stine, O Colin et al. (2009) Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 150B:282-9
Hong, L Elliot; Turano, Kathleen A; O'Neill, Hugh et al. (2008) Refining the predictive pursuit endophenotype in schizophrenia. Biol Psychiatry 63:458-64

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