) We propose to study the evolution of hippocampal dysfunction in the early stage of psychosis (ESOP). Smaller hippocampal volume is one of the most robust structural brain abnormalities in patients with schizophrenia. In addition, there is now compelling evidence for an abnormality of hippocampal activity in schizophrenia. However, it is unclear when in the disease process hippocampal structure and function become abnormal and which regions of the hippocampus are affected. Clarifying these questions will improve our understanding of the disease mechanism and our ability to intervene in the disease process. We will recruit patients at an early stage of their emerging psychotic disorder to study hippocampal structure with high-field 7T magnetic resonance imaging and hippocampal activity with 3T magnetic resonance mapping of cerebral blood volume (CBV) and BOLD signal. We will measure performance on tests of relational memory, a form of hippocampus-dependent memory that is impaired in schizophrenia. We will follow patients for 2 years and measure the change of hippocampal volume in psychotic disorders. We predict that hippocampal activity is abnormal already at the onset of the illness and does not change significantly over the course of the illness. As a consequence of abnormal activity, memory function is already moderately impaired at illness onset. Over the course of the first 2 years of illness, the abnormally increased activity of the hippocampus leads to structural changes in the hippocampus. This structural change is associated with a further progression of memory deficits. To test our hypotheses, we will develop two types of high-resolution hippocampal maps. First, anatomical maps will distinguish the volume of four sectors and two regions throughout the entire anterior-posterior extent of the hippocampus. Using this high-resolution parcellation of the hippocampus, we will test the hypothesis that the anterior sector CA1 is primarily affected in psychotic disorder patients. Second, functional maps will assess CBV and BOLD signal in the four sectors and two regions of the hippocampus. With these maps we will test the hypothesis of decreased hippocampal inhibition in psychotic disorders. We will correlate the measures of hippocampal structure and activity with the performance on tests of relational memory, a form of hippocampus- dependent memory that is impaired in schizophrenia. The proposed longitudinal study design will allow us to study the timing of hippocampal dysfunction in psychotic disorders. The goal of this research project is the identification of hippocampal markers for the early diagnosis of psychotic disorders.

Public Health Relevance

The proposed research will study the evolution of hippocampal dysfunction in the early stage of psychosis. The goal is the improved diagnosis and a better understanding of the disease mechanism of psychotic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH070560-07A1
Application #
8627720
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Rumsey, Judith M
Project Start
2004-04-01
Project End
2018-07-31
Budget Start
2013-09-27
Budget End
2014-07-31
Support Year
7
Fiscal Year
2013
Total Cost
$492,748
Indirect Cost
$177,221
Name
Vanderbilt University Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Talati, Pratik; Rane, Swati; Donahue, Manus J et al. (2016) Hippocampal arterial cerebral blood volume in early psychosis. Psychiatry Res 256:21-25
Woodward, Neil D; Heckers, Stephan (2016) Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders. Biol Psychiatry 79:1016-25
Ridgewell, Caitlin; Blackford, Jennifer Urbano; McHugo, Maureen et al. (2016) Personality traits predicting quality of life and overall functioning in schizophrenia. Schizophr Res :
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
Heckers, Stephan; Konradi, Christine (2015) GABAergic mechanisms of hippocampal hyperactivity in schizophrenia. Schizophr Res 167:4-11
Talati, Pratik; Rane, Swati; Skinner, Jack et al. (2015) Increased hippocampal blood volume and normal blood flow in schizophrenia. Psychiatry Res 232:219-25
Woodward, Neil D; Heckers, Stephan (2015) Brain Structure in Neuropsychologically Defined Subgroups of Schizophrenia and Psychotic Bipolar Disorder. Schizophr Bull 41:1349-59
Blackford, J U; Williams, L E; Heckers, S (2015) Neural correlates of out-group bias predict social impairment in patients with schizophrenia. Schizophr Res 164:203-9
Talati, Pratik; Rane, Swati; Kose, Samet et al. (2014) Increased hippocampal CA1 cerebral blood volume in schizophrenia. Neuroimage Clin 5:359-64

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