Project Summary

Ruben Gur, Ph.D. (Distinguished Investigator 2007) of the University of Pennsylvania, notes that growing evidence suggests that schizophrenia is a neurodevelopmental disorder affecting the temporal-limbic brain systems. Neuropsychological tests and structural and functional imaging studies all demonstrate impairments in memory, attention and emotion processing while also revealing corresponding structural abnormalities in the temporal and frontal areas of the brain underlying these cognitive domains. As these measures identify vulnerability markers for schizophrenia, they can more directly be linked to gene action. Dr. Gur has developed a serious of neurocognitive and emotion processing tests that has yielded good results in identifying behavioral characteristics related to schizophrenia. Using a combination of data obtained from post-mortem brain studies and a sample of over 900 patients, family members and healthy controls who have participated in the neurocognitive assessments and have provided blood samples for genotyping, Dr. Gur will attempt to develop a human model equivalent to a mouse model which has demonstrated an observation-based behavioral measure of sociability (equated with the negative symptoms of schizophrenia) sensitive to genetic manipulation in two strains of genetically engineered mice (C57BL/6J and BALB/cJ). He will focus on two brain regions most implicated in social behavior and which show impairment in schizophrenia—the amygdala and orbital frontal regions. Dr. Gur believes the results from this study could result in additional funding, and will aid in elucidating the genetic and neurobiological underpinnings of schizophrenia and other psychiatric disorders.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS

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