Significant and widespread cognitive impairments are a core feature of schizophrenia, providing a window into underlying neuropathophysiology while serving as a robust predictor of long-term functional outcome. The recently completed Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project demonstrates the commitment of the NIMH to enhancing our understanding of cognitive deficits in schizophrenia. Within the context of research in first episode schizophrenia at the Zucker Hillside Hospital, neurocognition is considered both as a critical target of treatment and as a predictor or mediator of illness course. The primary aims of this proposed CIDAR project involve the use of early neurocognitive measures to predict functional outcome during a 52-week controlled treatment algorithm, as well as acute symptomatic response during the initial 12-week randomized clinical trial. At the same time, measures collected over the course of this project will also serve as outcome variables for other projects in this CIDAR, including Project 2 (Magnetic Resonance Imaging) and Project 4 (Pharmacogenomics). We will utilize the MATRICS battery composite score to predict long-term (52-week) functional outcome in employment, residential status, and social functioning. In addition to the traditional neuropsychological measures in the MATRICS battery, the proposed project will employ complementary methods, derived from recent cognitive neuroscience research. Such measures are designed to more specifically assess functions sensitive to dopaminergic tone and other aspects of prefrontal cortico-cortical and cortico-subcortical circuits critical to illness and treatment. In particular, we aim to predict positive symptom response secondary to dopaminergic modulation by second-generation antipsychotics, after 12- and 52-weeks of treatment, using a set of tests (N-Back working memory test, Competing Programs, and Intradimensional/Extradimensional Set Shifting) that have been empirically demonstrated to be sensitive to dopamine manipulations and/or COMT genotype. We also hypothesize that specific tasks tapping motivation and behavioral production will predict negative symptom response, and semantic processing measures will predict disorganized symptoms. Finally, we will explore the possibility that early changes in cognition (between baseline and 12 weeks) may also be predictors of long term response and outcome, insofar as early improvement may reflect neural plasticity phenomena related to symptom remission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH080173-02
Application #
7851521
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2009
Total Cost
$519,580
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Karlsgodt, Katherine H; Bato, Angelica A; Ikuta, Toshikazu et al. (2018) Functional Activation During a Cognitive Control Task in Healthy Youth Specific to Externalizing or Internalizing Behaviors. Biol Psychiatry Cogn Neurosci Neuroimaging 3:133-140
Chang, E H; Fernando, K; Yeung, L W E et al. (2018) Single point mutation on the gene encoding dysbindin results in recognition deficits. Genes Brain Behav 17:e12449
John, Majnu; Lencz, Todd; Malhotra, Anil K et al. (2018) A simulations approach for meta-analysis of genetic association studies based on additive genetic model. Meta Gene 16:143-164
DeRosse, Pamela; Nitzburg, George C; Blair, Melanie et al. (2018) Dimensional symptom severity and global cognitive function predict subjective quality of life in patients with schizophrenia and healthy adults. Schizophr Res 195:385-390
Lyall, A E; Pasternak, O; Robinson, D G et al. (2018) Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry 23:701-707
Shafritz, Keith M; Ikuta, Toshikazu; Greene, Allison et al. (2018) Frontal lobe functioning during a simple response conflict task in first-episode psychosis and its relationship to treatment response. Brain Imaging Behav :
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
Damle, Nishad R; Ikuta, Toshikazu; John, Majnu et al. (2017) Relationship among interthalamic adhesion size, thalamic anatomy and neuropsychological functions in healthy volunteers. Brain Struct Funct 222:2183-2192
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
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

Showing the most recent 10 out of 86 publications