The purpose of this Mentored Patient-Oriented Research Career Development (K23) Award is to study the linkage between substance abuse and the subsequent development of schizophrenia in adolescents and young adults. A key element in understanding this linkage may be the decision-making process: In substance abuse, a dysfunction of the brain reward circuit may result in an impairment in decision-making only when there is an immediate reward expectancy. In schizophrenia, a prefrontal cortical deficit may result in an impairment in decision-making independent of immediate reward expectancy. This award has three specific aims for investigating this assumption: (1) to assess and compare decision-making tasks with and without immediate reward expectancy between cannabis abusers with and without schizophrenia, patients with schizophrenia and no substance abuse, and normal controls; (2) to examine the association between the decision-making process, negative symptoms, and neurocognitive functions of the prefrontal cortex in schizophrenia patients initially and after one year of treatment; (3) to examine the association between decision-making and variables such as gender, conduct and antisocial personality disorders, impulse control disorders, and symptom dimensions. Major career development activities of this award are (1) didactic programs in decision-making and cognitive assessments of the prefrontal cortex; (2) participation in a large ongoing clinical trial comparing patients experiencing their first episode of psychosis, with and without a history of substance abuse, following them for treatment response and neurocognition; (3) the design, conduct and analyses of a study using computerized decision-making tasks with and without immediate reward. Long-term objectives of this award are: (1) to gain expertise in the psychiatric consequences of addiction; (2) to develop research programs at Hillside Hospital aimed at improving the care of dual-diagnosis patients; (3) to introduce the field of decision-making in research and clinical programs at Hillside Hospital. This revised application has been strengthened by (1) focusing the research project on cannabis abuse, which will result in the study of more homogenous groups of patients and increased statistical power; (2) adding training in neuroscience and neuroimaging; and (3) clarifying the study design with additional information pertaining to the first-psychotic episode study.
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