The first episode of schizophrenia may be the most critical period to examine mechanisms that influence treatment response and outcome of this chronically disabling disorder. Moreover, the examination of first episode patients provides a unique opportunity to study the biological basis of response without the potential confounds of prolonged antipsychotic drug exposure and other factors related to chronicity. The proposed Zucker Hillside Hospital (ZHH) CIDAR will integrate the extensive clinical experience of ZHH researchers focused on the treatment of first episode schizophrenia, with the expertise of investigators utilizing neurocognitive, neuroimaging, and molecular genetic approaches to identify biological predictors of treatment response and functional outcome. The proposed ZHH CIDAR will draw on a large number (n=242) of first episode schizophrenia patients to be enrolled in an NIMH-funded 12-week double-blind randomized clinical trial of risperidone versus aripiprazole (2R01 MH 60004). Funding of this CIDAR application will permit retention of these subjects for a full year of regular, reliable assessments of symptoms and side effects, in the context of a standardized, open-label treatment algorithm with risperidone and aripiprazole (or clozapine in treatment refractory patients) for the remainder of a total 52-week study period. Analyses will involve evaluating the ability of neurocognitive, neuroimaging, and molecular genetic variation to resolve the heterogeneity of short- and long-term response assessed comprehensively across a range of symptomatic, metabolic, neurocognitive and functional domains. Specifically, the ZHH CIDAR Operations and Clinical Assessment, Research Methods (cognitive neuroscience) and Special Scientific Procedures (genomics) cores will provide infrastructure for the following four projects: (1) Neurocognitive function and treatment response in first episode schizophrenia;(2) MR Imaging predictors of response and outcome in first episode schizophrenia;(3) Evaluation of striatal D2/D3 receptor availability in first episode schizophrenia;(4) Pharmacogenomics of treatment response in first episode schizophrenia. We believe the ZHH CIDAR represents a unique opportunity to dissect the heterogeneity of treatment response in a first episode cohort with minimal or no prior antipsychotic treatment and that the proposed work will lead to improved treatment as patients enter a critical phase of their illness. In addition, we expect that completing the proposed studies will facilitate the emergence of empirically-based strategies to individualize patient care and provide new data towards the development of the next generation of antipsychotic drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
3P50MH080173-05S2
Application #
8509311
Study Section
Special Emphasis Panel (ZMH1-ERB-C (01))
Program Officer
Hillefors, MI
Project Start
2008-05-09
Project End
2014-04-30
Budget Start
2012-07-18
Budget End
2014-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$553,557
Indirect Cost
$148,837
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

Showing the most recent 10 out of 78 publications