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 #
3P50MH080173-05S1
Application #
8494910
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
2012-05-16
Budget End
2014-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$256,070
Indirect Cost
$101,811
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Schwehm, Andrew; Robinson, Delbert G; Gallego, Juan A et al. (2016) Age and Sex Effects on White Matter Tracts in Psychosis from Adolescence through Middle Adulthood. Neuropsychopharmacology 41:2473-80
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
Sarpal, Deepak K; Argyelan, Miklos; Robinson, Delbert G et al. (2016) Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment. Am J Psychiatry 173:69-77
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
Robinson, Delbert G; Gallego, Juan A; John, Majnu et al. (2015) A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes. Schizophr Bull 41:1227-36
Trampush, Joey W; Lencz, Todd; Knowles, Emma et al. (2015) Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment. Am J Med Genet B Neuropsychiatr Genet 168B:363-73
Zhang, Jian-Ping; Robinson, Delbert G; Gallego, Juan A et al. (2015) Association of a Schizophrenia Risk Variant at the DRD2 Locus With Antipsychotic Treatment Response in First-Episode Psychosis. Schizophr Bull 41:1248-55
Wheeler, Anne L; Wessa, Michèle; Szeszko, Philip R et al. (2015) Further neuroimaging evidence for the deficit subtype of schizophrenia: a cortical connectomics analysis. JAMA Psychiatry 72:446-55
Chang, Eric H; Kirtley, Anne; Chandon, Toni-Shay S et al. (2015) Postnatal neurodevelopmental expression and glutamate-dependent regulation of the ZNF804A rodent homologue. Schizophr Res 168:402-10
DeRosse, Pamela; Nitzburg, George C; Ikuta, Toshikazu et al. (2015) Evidence from structural and diffusion tensor imaging for frontotemporal deficits in psychometric schizotypy. Schizophr Bull 41:104-14

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