Neurochemical brain imaging studies conducted over the past two decades have largely focused on the evaluation of the dopamine system, in particular the striatal D2/D3 dopamine receptor. These studies have evaluated differences in striatal D2/D3 receptor availability between unmedicated patients and demographically matched controls and assessed the time course and magnitude of occupancy of striatal D2/D3 receptors by first and second generation antipsychotic medications. The findings of the occupancy studies have yielded valuable and consistent information with respect to identifying relationships between plasma drug concentrations and receptor occupancy and a therapeutic window for symptom improvement and side effects. However, the data are less consistent with respect to whether striatal D2/D3 receptor availability in the unmedicated state is normal or altered in patients compared to controls, in part perhaps because prior studies were conducted largely in patients who had been previously treated with antipsychotic medications. In addition, the variability between studies and the failure to detect a difference between patients and controls may be related to a lack of consideration of such variables as symptoms at the time of scanning, clinical treatment outcome and D2/D3 receptor polymorphisms.
The specific aims of the project are to evaluate striatal dopamine (D2/D3) receptor availability in first episode schizophrenia patients prior to treatment and to evaluate the association between baseline striatal dopamine (D2/D3) receptor availability and the variance observed between patients in the CIDAR treatment trial, such as symptom response and side effects. Relationship to polymorphisms in dopamine-related genes will also be examined. 65 patients and 40 normal comparison subjects will undergo a Positron Emission Tomography (PET) scan using the well established dopamine (D2/D3) receptor radiotracer [11C]-raclopride. The patients will be antipsychotic naive and will be scanned prior to starting treatment. Having accomplished the specific aims of this project, unique data will be obtained regarding striatal D2/D3 receptor availability in patients with schizophrenia prior to initiating antipsychotic treatment and the relationship to clinical and genetic variables.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH080173-05
Application #
8377119
Study Section
Special Emphasis Panel (ZMH1-ERB-C)
Project Start
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$167,970
Indirect Cost
$66,783
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Trampush, J W; Yang, M L Z; Yu, J et al. (2017) GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry 22:336-345
Chang, Eric H; Argyelan, Miklos; Aggarwal, Manisha et al. (2017) Diffusion tensor imaging measures of white matter compared to myelin basic protein immunofluorescence in tissue cleared intact brains. Data Brief 10:438-443
McNamara, Robert K; Szeszko, Philip R; Smesny, Stefan et al. (2017) Polyunsaturated fatty acid biostatus, phospholipase A2 activity and brain white matter microstructure across adolescence. Neuroscience 343:423-433
DeRosse, Pamela; Ikuta, Toshikazu; Karlsgodt, Katherine H et al. (2017) White Matter Abnormalities Associated With Subsyndromal Psychotic-Like Symptoms Predict Later Social Competence in Children and Adolescents. Schizophr Bull 43:152-159
John, Majnu; Ikuta, Toshikazu; Ferbinteanu, Janina (2017) Graph analysis of structural brain networks in Alzheimer's disease: beyond small world properties. Brain Struct Funct 222:923-942
Chang, Eric H; Argyelan, Miklos; Aggarwal, Manisha et al. (2017) The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains. Neuroimage 147:253-261
John, Majnu; Lencz, Todd; Ferbinteanu, Janina et al. (2017) Applications of temporal kernel canonical correlation analysis in adherence studies. Stat Methods Med Res 26:2437-2454
Lyall, A E; Pasternak, O; Robinson, D G et al. (2017) Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry :
Howrigan, D P; Simonson, M A; Davies, G et al. (2016) Genome-wide autozygosity is associated with lower general cognitive ability. Mol Psychiatry 21:837-43
Sarpal, Deepak K; Lencz, Todd; Malhotra, Anil K (2016) In Support of Neuroimaging Biomarkers of Treatment Response in First-Episode Schizophrenia. Am J Psychiatry 173:732-3

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