Abnormalities in smooth pursuit eye movements and deficits in auditory sensory gating are two of the best characterized physiological endophenotypes associated with schizophrenia. Transient normalization of both of these sensory deficits by smoking, in addition to evidence from epidemiology, animal models, genetics, molecular biology and post-mortem binding studies, suggests involvement of nicotinic cholinergic receptors in the disease. The functional effect of this putative cholinergic dysfunction on mental processes in individuals with schizophrenia, however, remains unknown.
This first aim of this study proposes the use of functional magnetic resonance imaging (fMRl) to characterize the functional neuroanatomy associated with smooth pursuit eye movements in patients with schizophrenia and age-matched healthy controls to determine if failure to properly execute this task in patients with schizophrenia is associated with a detectable, abnormal pattern of neuronal activation.
The second aim of his study is to use fMRI to detect differences in functional neuroanatomy between control and patients with schizophrenia are due to nicotinic cholinergic receptor dysfunction by examining task-specific (smooth pursuit eye movement) changes in neuronal activity associated with administration of nicotine to controls and patients with schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH066533-02
Application #
6619735
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Desmond, Nancy L
Project Start
2002-08-01
Project End
2003-10-31
Budget Start
2003-08-01
Budget End
2003-10-31
Support Year
2
Fiscal Year
2003
Total Cost
$10,642
Indirect Cost
Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Smucny, Jason; Olincy, Ann; Eichman, Lindsay S et al. (2015) Neuronal effects of nicotine during auditory selective attention. Psychopharmacology (Berl) 232:2017-28
Tregellas, Jason R; Smucny, Jason; Harris, Josette G et al. (2014) Intrinsic hippocampal activity as a biomarker for cognition and symptoms in schizophrenia. Am J Psychiatry 171:549-56
Smucny, Jason; Olincy, Ann; Eichman, Lindsay C et al. (2013) Early sensory processing deficits predict sensitivity to distraction in schizophrenia. Schizophr Res 147:196-200
Smucny, Jason; Wylie, Korey; Rojas, Donald et al. (2013) Evidence for gamma and beta sensory gating deficits as translational endophenotypes for schizophrenia. Psychiatry Res 214:169-74
Tregellas, Jason R; Tanabe, Jody L; Martin, Laura F et al. (2005) FMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia. Am J Psychiatry 162:391-3
Tregellas, Jason R; Tanabe, Jody L; Miller, David E et al. (2004) Neurobiology of smooth pursuit eye movement deficits in schizophrenia: an fMRI study. Am J Psychiatry 161:315-21