The broad aim of this five year study is to advance our understanding of language dysfunction in schizophrenia spectrum disorder using event-related potential, event-related gamma, experimental neuropsychological and clinical measures in three DSM-IV diagnosed clinical groups: chronic schizophrenia (CS), first episode schizophrenia (FES) and schizotypal personality disorder (SPD), and their matched normal controls. The use of the three clinical groups will afford studying both differences and similarities in language impairment across the schizophrenia spectrum. Similarities and differences in language processing in males and females in these three clinical groups will be studied as a secondary goal. In order to arrive at a comprehensive model of language dysfunction in the schizophrenia spectrum, we will use a heuristic model of language in which semantic organization includes three distinct but interacting components referred to as properties, processes, and content of semantic networks. Properties refer to connectivity weights among words, and to the size and the coherence of networks. Processes refer to activation, inhibition, and context use (both local and global). Network contents including words, numbers, and symbols will not be measured. We propose a gradual breakdown in language function with most impairment in CS>FES>SPD. We will test these hypotheses in a five-year study of three schizophrenia spectrum groups: 1) 30 patients with CS; 2) 30 patients with FES; and 3) 30 individuals with SPD, and 30 normal controls matched to each clinical group (n=90). Each control group will be matched for age, gender and parental SES to its respective clinical group and all subjects will be right handed, with English as their primary language. We will use ERP, event-related gamma, experimental neuropsychological, and clinicaldata (Thought Disorder Index TDI), to study language disorder in the three clinical groups. We thus predict over-activation in semantic networks as indexed by the N400, word-pair study at short stimulus onset asynchrony (SOA) in SPD, FES, and CS. The evidence of abnorma inhibitory/context utilization processes will be found in the N400, sentence and paragraph studies, with most severe impairment in CS>FES>SPD. The evidence of abnormal properties in semantic networks will be found in the neuropsychological study of word recall, in the N400, word-pair, short SOA study, and in the event-related gamma data, it FES and CS, but not in SPD. Correlational analyses among the four data sets will seek to characterize the relationships among the four domains of analysis.We predict that females will show less impairment than males on all these measures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063360-05
Application #
7075440
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Meinecke, Douglas L
Project Start
2002-06-10
Project End
2007-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$161,733
Indirect Cost
Name
Harvard University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Liu, Taosheng; Pinheiro, Ana P; Zhao, Zhongxin et al. (2016) Simultaneous face and voice processing in schizophrenia. Behav Brain Res 305:76-86
Nestor, Paul G; Nakamura, Motoaki; Niznikiewicz, Margaret et al. (2015) Attentional Control and Intelligence: MRI Orbital Frontal Gray Matter and Neuropsychological Correlates. Behav Neurol 2015:354186
Nestor, Paul G; Choate, Victoria; Niznikiewicz, Margaret et al. (2014) Neuropsychology of reward learning and negative symptoms in schizophrenia. Schizophr Res 159:506-8
Pinheiro, Ana P; Rezaii, Neguine; Rauber, Andréia et al. (2014) Abnormalities in the processing of emotional prosody from single words in schizophrenia. Schizophr Res 152:235-41
Nestor, Paul G; Nakamura, Motoaki; Niznikiewicz, Margaret et al. (2013) In search of the functional neuroanatomy of sociality: MRI subdivisions of orbital frontal cortex and social cognition. Soc Cogn Affect Neurosci 8:460-7
Nestor, Paul G; Kubicki, Marek; Nakamura, Motoaki et al. (2013) Neuropsychological variability, symptoms, and brain imaging in chronic schizophrenia. Brain Imaging Behav 7:68-76
Nestor, Paul G; Klein, Kristy; Pomplun, Marc et al. (2010) Gaze cueing of attention in schizophrenia: individual differences in neuropsychological functioning and symptoms. J Clin Exp Neuropsychol 32:281-8
Nestor, Paul G; Niznikiewicz, Margaret; McCarley, Robert W (2010) Distinct contribution of working memory and social comprehension failures in neuropsychological impairment in schizophrenia. J Nerv Ment Dis 198:206-12
Niznikiewicz, M; Mittal, M Singh; Nestor, P G et al. (2010) Abnormal inhibitory processes in semantic networks in schizophrenia. Int J Psychophysiol 75:133-40
Niznikiewicz, Margaret A; Spencer, Kevin M; Dickey, Chandlee et al. (2009) Abnormal pitch mismatch negativity in individuals with schizotypal personality disorder. Schizophr Res 110:188-93

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