This application for a Mentored Patient-oriented Career Development Award (K23) is to support the development of the candidate into a independent investigator capable of conducting large scale clinical trials in psychiatry that address issues of treatment efficacy and effectiveness in addition to serving as the clinical basis for pharmacogenetic studies. The development plan has four major goals: 1) Gain expertise in the design of a clinical trial in schizophrenia, 2) Participate in the execution of a clinical trial, 3) Utilize statistical methodology to analyze clinical trials studies, and 4) Conduct pharmacogenetic analyses of clinical trials data. To accomplish these aims, three major career development activities are proposed: 1) A didactic program to prepare the candidate to independently design, conduct, and analyze clinical trials, 2) Participation in a large clinical trial comparing new antipsychotic medications in patients experiencing their first episode of schizophrenia. This will involve the candidate's participation in the clinical trial as an investigator and will provide the opportunity to develop a pharmacogenetic protocol and, 3) The design, conduct and analysis of a pilot study of the effects of adding the serotonin re-uptake inhibitor, sertraline, to the antipsychotic treatment regimen of schizophrenia patients with treatment-refractory hallucinations. The research plan incorporates two studies. The first is a pharmacogenetic assessment of response to the antipsychotic agents olanzapine and risperidone. This study involves determination of genotype at specific candidate loci within the dopamine and Serotonin receptor systems and case-control and family-based association analysis between these loci and clinical phenotypes of treatment response, drug-induced weight gain and drug-induced extra pyramidal symptoms. The second study is a clinical trial examining sertraline augmentation in schizophrenia patients with hallucinations. The basis of this study is evidence from clinical trials research as well as molecular genetics. This represents an initial effort to utilize the two distinct methodologies to enhance the treatment of schizophrenia. The career development activities and completion of the research studies described in this application are expected to provide the candidate with the knowledge and research experience to develop into an independent investigator with the expertise to conduct high quality clinical trials that incorporate pharmacogenetics into psychiatry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH001760-02
Application #
6185259
Study Section
Treatment Assessment Review Committee (TA)
Program Officer
Light, Enid
Project Start
1999-09-01
Project End
2004-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$155,882
Indirect Cost
Name
Long Island Jewish Medical Center
Department
Type
DUNS #
City
New Hyde Park
State
NY
Country
United States
Zip Code
11040
Franke, Barbara; Stein, Jason L; Ripke, Stephan et al. (2016) Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nat Neurosci 19:420-431
Zhang, Jian-Ping; Lencz, Todd; Geisler, Stephen et al. (2013) Genetic variation in BDNF is associated with antipsychotic treatment resistance in patients with schizophrenia. Schizophr Res 146:285-8
Lee, S Hong; DeCandia, Teresa R; Ripke, Stephan et al. (2012) Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat Genet 44:247-50
Correll, Christoph U; Lops, Johnny D; Figen, Vicki et al. (2011) QT interval duration and dispersion in children and adolescents treated with ziprasidone. J Clin Psychiatry 72:854-60
Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43:969-76
Lencz, Todd; Robinson, Delbert G; Napolitano, Barbara et al. (2010) DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenet Genomics 20:569-72
Lencz, Todd; Szeszko, Philip R; DeRosse, Pamela et al. (2010) A schizophrenia risk gene, ZNF804A, influences neuroanatomical and neurocognitive phenotypes. Neuropsychopharmacology 35:2284-91
Narr, Katherine L; Szeszko, Philip R; Lencz, Todd et al. (2009) DTNBP1 is associated with imaging phenotypes in schizophrenia. Hum Brain Mapp 30:3783-94
Lencz, Todd; Lipsky, Robert H; DeRosse, Pamela et al. (2009) Molecular differentiation of schizoaffective disorder from schizophrenia using BDNF haplotypes. Br J Psychiatry 194:313-8
Penzner, Julie B; Dudas, Melissa; Saito, Ema et al. (2009) Lack of effect of stimulant combination with second-generation antipsychotics on weight gain, metabolic changes, prolactin levels, and sedation in youth with clinically relevant aggression or oppositionality. J Child Adolesc Psychopharmacol 19:563-73

Showing the most recent 10 out of 35 publications