We are requesting support for a study of brain sensorimotor abnormalities in childhood onset psychotic illnesses. Motor deficits are consistently found in psychotic patient populations and have also been identified as among a few promising early childhood risk factors for psychosis. We will employ a combination of neurobehavioral methods with non-invasive neuroimaging using magnetoencephalography (MEG) and structural magnetic resonance imaging (MRI). Eighty young participants with either childhood onset psychotic bipolar disorder (N=40) or schizophrenia (N=40) will be compared to age and gender matched comparison subjects (N=40) without personal or family history of psychotic and/or bipolar mood disorders. Our general perspective on motor coordination deficits is two-fold. First, we propose that a failure in inter-hemispheric motor inhibition results in failures to properly coordinate timing signals in bimanual coordination. Second, we believe that a failure in feed-forward efferent copy mechanisms from motor to somatosensory cortex results in improper perceptual feedback during patient's own movements. Our long term goals for this research are to refine the neurobiology of motor deficits in psychotic disorders, develop biomarkers for future family-based studies of genetic risk and evaluate neurobiological differences between schizophreniform and mood-related psychotic illnesses. Some of these biomarkers should be associated with psychosis per se and others with more disorder specific clinical manifestations. Such knowledge could a) contribute to earlier and more accurate diagnosis, b) lead to improved treatment planning at onset of illness, c) assist with more accurate estimate of illness trajectory and prognosis, d) aid in the development of possible new endophenotypic markers for psychosis, and e) form the basis for future family studies relating to genetic vs. developmental contributions to these disorders.

Public Health Relevance

Psychotic illnesses including schizophrenia and bipolar disorder with psychotic features are significant public health concerns. Although much focus has been given to specific risk factors for each illness, little attention has been paid to factors in common between the disorders (i.e., a dimensional approach rather than categorical approach to risk factors). Impaired motor behavior is a promising risk factor for psychoses broadly defined. Our long term goals for this research are to refine the neurobiology of motor deficits in psychotic disorders across category and develop biomarkers for future family-based studies of genetic risk. Some of these biomarkers should be associated with psychosis per se and others with more disorder specific clinical manifestations (e.g., specific to schizophrenia). Such knowledge could a) contribute to earlier and more accurate diagnosis, b) lead to improved treatment planning at onset of illness, c) assist with more accurate estimate of illness trajectory and prognosis, d) aid in the development of possible new endophenotypic markers for psychosis, and e) form the basis for future family studies relating to genetic vs. developmental contributions to these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH081920-04
Application #
8240095
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Garvey, Marjorie A
Project Start
2009-06-01
Project End
2014-03-31
Budget Start
2012-05-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$341,921
Indirect Cost
$119,171
Name
University of Colorado Denver
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
McFadden, Kristina L; Steinmetz, Sarah E; Carroll, Adam M et al. (2014) Test-retest reliability of the 40 Hz EEG auditory steady-state response. PLoS One 9:e85748
Wilson, Tony W; Slason, Erin; Asherin, Ryan et al. (2011) Abnormal gamma and beta MEG activity during finger movements in early-onset psychosis. Dev Neuropsychol 36:596-613
Wilson, Tony W; Slason, Erin; Asherin, Ryan et al. (2010) An extended motor network generates beta and gamma oscillatory perturbations during development. Brain Cogn 73:75-84