The thalamus is both a major relay station of sensory and perceptual information to the cortex as well as an important reciprocal participant in cortical action. These roles, both relevant to the sensory processing and executive action deficits in schizophrenia, make the thalamus a leading candidate structure for the defective link in the neural circuits involved in the disease diathesis. During the first 3 years of this project we have developed reliable methods for outlining the medial dorsal nucleus, the pulvinar, and the centromedian nucleus and applied these techniques to the high-resolution MRI of 101 subjects, 41 unmedicated patients with schizophrenia and 60 normal controls and a group of 12 patients with schizotypal personality disorder. This confirmed smaller volumes of the medial dorsal and pulvinar in patients with schizophrenia and the pulvinar alone in patients with schizotypal personality disorder. Coregistered positon emission tomography scans with 18F-doxyglucose were available on the group of 101 and reduced metabolic rates in the medial dorsal and centromedian nuclei were confirmed. We obtained identical MRI on a total of 240 patients with schizophrenia ages 13-65, 78 patients with schizotypal disorder, and 223 normal controls (a total of 541 subjects) and have these images on line and ready for tracing. We carried out 2 functional MRI studies on the thalamus in normal controls with confirmation of functional activation in pulvinar and medial dorsal nucleus in attentional paradigms. In the next 4 years we propose 1) to develop methods for tracing the anterior nucleus of the thalamus, and trace the 4 nuclei in these subjects 2) to examine the relationship of age, sex, illness outcome and symptom patterns to thalamic nuclear volumes 3) contrast fMRI activation in normals and unmedicated and never medicated patients with schizophrenia using MRI templates for regional nuclear assessment and test interregional correlations in volume and activity 4) assess diffusion tensor anisotropy and angle of diffusion orientation in the internal capsule adjacent to the thalamus 5) examine correlations between nuclear volume and volume of regions of the brain that are reciprocally linked including the cingulate gyrus, the caudate and putamen, and the 44 Brodmann areas of the cortex. This project brings together the resources and imaging/anatomical researchers of the Mount Sinai Department of Psychiatry, the Neuroscience PET laboratory and the Department of Radiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060023-07
Application #
7387447
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Rumsey, Judith M
Project Start
1999-08-01
Project End
2009-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
7
Fiscal Year
2008
Total Cost
$390,140
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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Mitelman, Serge A; Canfield, Emily L; Brickman, Adam M et al. (2010) Progressive ventricular expansion in chronic poor-outcome schizophrenia. Cogn Behav Neurol 23:85-8
Segal, Devorah; Haznedar, M Mehmet; Hazlett, Erin A et al. (2010) Diffusion tensor anisotropy in the cingulate gyrus in schizophrenia. Neuroimage 50:357-65
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Hazlett, Erin A; Byne, William; Brickman, Adam M et al. (2010) Effects of sex and normal aging on regional brain activation during verbal memory performance. Neurobiol Aging 31:826-38
Mitelman, Serge A; Canfield, Emily L; Chu, King-Wai et al. (2009) Poor outcome in chronic schizophrenia is associated with progressive loss of volume of the putamen. Schizophr Res 113:241-5
Schneiderman, Jason S; Buchsbaum, Monte S; Haznedar, M Mehmet et al. (2009) Age and diffusion tensor anisotropy in adolescent and adult patients with schizophrenia. Neuroimage 45:662-71

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