Certain traits that are not necessarily psychotic in appearance are more prevalent in the families of schizophrenic patients than they are in the general population. We have identified and studied several of these traits using them as supplementary phenotypes in linkage analysis and also as guides to the pathophysiology of schizophrenia. Here we propose studies of two of the major traits we have previously, identified as being significantly associated with schizophrenic psychosis and also occurring prominently in the unaffected biological family members of the patients: eye tracking dysfunctions (ETD) and spatial working memory impairments. Our research has shown that a major component of ETD is a defect in motion perception. We propose to follow up this finding to see whether the raised motion discrimination thresholds observed in patients also occur in unaffected relatives. Further, using psychophysical method we will study whether local or global motion processing is involved in the impairments, a result that has consequences for the brain localization of ETD. fMRl scanning of patients and relatives viewing pursuit, saccade, and pure motion targets will be undertaken to supply physiological information about the brain localization of the eye tracking defect and as support or disconfirmation of the psychophysical studies. The second trait, spatial working memory, will be studied along side of two kinds of object working memory to discern whether other domains of working memory are also impaired. The modularity of working memory domains has consequences for specifying the pathophysiology of schizophrenia. We will compare performance on spatial and object working memory, the latter using two very different kinds of stimuli: memory for faces and memory for snowflakes. The first has an immediacy and cogency not present in the perception of other objects, and there probably is also a dedicated neural hardware for face perception. Perception of snowflakes, on the other hand, tests object working memory without a verbal component. fMRl of patients and relatives while performaning these working tasks will also be undertaken.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH031340-29
Application #
6937707
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Lehner, Thomas
Project Start
1978-04-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
29
Fiscal Year
2005
Total Cost
$322,000
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Morgan, Charity J; Coleman, Michael J; Ulgen, Ayse et al. (2017) Thought Disorder in Schizophrenia and Bipolar Disorder Probands, Their Relatives, and Nonpsychiatric Controls. Schizophr Bull 43:523-535
Deutsch, Curtis K; Levy, Deborah L; Price, Selya F R et al. (2015) Quantitative Measures of Craniofacial Dysmorphology in a Family Study of Schizophrenia and Bipolar Illness. Schizophr Bull 41:1309-16
Morgan, Charity J; Lenzenweger, Mark F; Rubin, Donald B et al. (2014) A hierarchical finite mixture model that accommodates zero-inflated counts, non-independence, and heterogeneity. Stat Med 33:2238-50
Coleman, Michael J; Titone, Debra; Krastoshevsky, Olga et al. (2010) Reinforcement ambiguity and novelty do not account for transitive inference deficits in schizophrenia. Schizophr Bull 36:1187-200
Krause, Verena; Krastoshevsky, Olga; Coleman, Michael J et al. (2010) Tailoring the definition of the clinical schizophrenia phenotype in linkage studies. Schizophr Res 116:133-42
Levy, Deborah L; Coleman, Michael J; Sung, Heejong et al. (2010) The Genetic Basis of Thought Disorder and Language and Communication Disturbances in Schizophrenia. J Neurolinguistics 23:176
Levy, Deborah L; Sereno, Anne B; Gooding, Diane C et al. (2010) Eye tracking dysfunction in schizophrenia: characterization and pathophysiology. Curr Top Behav Neurosci 4:311-47
Coleman, Michael J; Cestnick, Laurie; Krastoshevsky, Olga et al. (2009) Schizophrenia patients show deficits in shifts of attention to different levels of global-local stimuli: evidence for magnocellular dysfunction. Schizophr Bull 35:1108-16
McCarthy, Shane E; Makarov, Vladimir; Kirov, George et al. (2009) Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet 41:1223-7
Sebat, Jonathan; Levy, Deborah L; McCarthy, Shane E (2009) Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders. Trends Genet 25:528-35

Showing the most recent 10 out of 73 publications