Postmortem Brain Tissue Examination in Neuropsychiatric

$0Z01FY2005MHNIH

National Institute Of Mental Health

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Abstract

The section collected 74 brains donated in the course of the last year. There are five areas of research for this project, as follows: 1. susceptibility genes and related genes for schizophrenia relative to normal controls primarily in dorsolateral prefrontal cortex (DLPFC) and hippocampus; 2. the effects of allelic variations in susceptibility genes on expression patterns of these same genes and related genes in DLPFC and hippocampus; 3. normal human brain development; 4. substance abuse and affective disorders; and 5. animal models of schizophrenia. Findings from studies of susceptibility genes and related genes for schizophrenia: 1. decreased mRNA expression of glutamatic acid decarboxylase (GAD1) in schizophrenics relative to contols in DLPFC; 2. increased mRNA expression in neuregulin (NRG1) in schizophrenics relative to controls in DLPFC; 3. decreased mRNA expression in binding partners of DISC1 (FEZ, LIS and NUDEL) in schizophrenics relative to controls in DLPFC and hippocampus. Findings from studies of the effects of allelic variations in susceptibility genes on the expression patterns of these same genes and related genes in human brain: 1. Allelic variations in GAD1 effect mRNA expression of GAD1 in DLPFC; 2. allelic variations in NRG1 that are part of a haplotype effect mRNa expression of type I and type IV isoforms of NRG1 in hippocampus; and 3. allelic variations in DISC1 effect mRNA expression of DISC1 binding partners including FEZ, LIS and NUDEL. Lastly, we are continuing our studies on normal human brain development across the lifespan, our studies of substance abuse including cocaine and marijuana in conjunction with our NIDA collaboraters and our animal model studies.

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