This is a revised proposal to study the structure and function of the hippocampal formation in psychosis. Hippocampal volume deficits are among the most robust brain abnormalities in chronic patients with schizophrenia. More recent studies have now established that hippocampal volume reduction is already present in the early stages of psychosis - in patients who develop schizophrenia as well as those who develop bipolar disorder. It is unclear, however, whether hippocampal pathology can explain the psychotic features or the well-known memory deficits in schizophrenia and bipolar disorder. Here the applicant is proposing to test the hypothesis that hippocampal dysfunction is necessary (but not sufficient) for the production of psychosis. Memory deficits are predicted to be prominent in schizophrenia and bipolar disorder because cortico-hippocampal interactions are perturbed in psychosis. To test this hypothesis, two groups of patients will be studied with novel morphometric and functional imaging approaches. First, two forms of hippocampal-dependent memory (i.e., the ability to remember episodes and the ability to infer relationships among items) will be studied in chronic patients with schizophrenia. This will allow the applicant to test the prediction that hippocampal dysfunction in conjunction with cortical and thalamic abnormalities can explain specific memory deficits in schizophrenia. Second, schizophrenic and bipolar patients will be studied at the time of their first hospitalization. Hippocampal function during episodic and relational memory task performance is predicted to be abnormal in the early stages of psychosis, whereas cortical dysfunction is less prominent compared to chronic patients with schizophrenia. The proposed studies are designed to elucidate the crucial role of hippocampal dysfunction for the production of psychosis and the development of cognitive deficits in schizophrenia and bipolar disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH070560-01A1
Application #
6870097
Study Section
Special Emphasis Panel (ZRG1-BDCN-B (01))
Program Officer
Meinecke, Douglas L
Project Start
2005-02-07
Project End
2005-12-31
Budget Start
2005-02-07
Budget End
2005-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$157,661
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
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Wilson, Jo Ellen; Heckers, Stephan; Ely, E Wesley et al. (2018) The authors reply. Crit Care Med 46:e722-e723
Avery, Suzanne N; Rogers, Baxter P; Heckers, Stephan (2018) Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging 3:423-432
Theiss, Justin D; Ridgewell, Caitlin; McHugo, Maureen et al. (2017) Manual segmentation of the human bed nucleus of the stria terminalis using 3T MRI. Neuroimage 146:288-292
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Ridgewell, Caitlin; Blackford, Jennifer Urbano; McHugo, Maureen et al. (2017) Personality traits predicting quality of life and overall functioning in schizophrenia. Schizophr Res 182:19-23
Woodward, Neil D; Heckers, Stephan (2016) Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders. Biol Psychiatry 79:1016-25
Talati, Pratik; Rane, Swati; Donahue, Manus J et al. (2016) Hippocampal arterial cerebral blood volume in early psychosis. Psychiatry Res Neuroimaging 256:21-25
Rane, Swati; Talati, Pratik; Donahue, Manus J et al. (2016) Inflow-vascular space occupancy (iVASO) reproducibility in the hippocampus and cortex at different blood water nulling times. Magn Reson Med 75:2379-87
Thakkar, Katharine N; Schall, Jeffrey D; Heckers, Stephan et al. (2015) Disrupted Saccadic Corollary Discharge in Schizophrenia. J Neurosci 35:9935-45

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