Brain Tissue Collection for Neuropathological Studies

The purpose of this study is to collect and study the brain tissue of deceased individuals to learn more about the nervous system and mental disorders. Information gained from donated tissue may lead to better treatments and potential cures for nervous system and mental disorders.

This study will ask relatives of deceased individuals to donate the brains of their deceased relatives to allow further study of neurological and psychiatric disorders.

The knowledge of how affected tissue deviates from normal control tissue is an integral part of fully understanding a neurological or psychiatric disorder. The purpose of this protocol is to establish a coordinating program with the pathology departments of the Washington D.C. and metropolitan area hospitals and local medical examiner's offices for the donation of brain tissue.

Dissected brain tissue from selected brain regions, including but not limited to the dorsolateral prefrontal cortex and hippocampal formation, will be assembled from large cohorts of normal controls and schizophrenic subjects. The expression of mRNA and protein for selected molecules, chosen on the basis of their genetic association with schizophrenia, will be measured with a variety of assays including but not limited to qPCR and Western blots.

Outcome measures are the statistical comparison within normal controls of mRNA and/or protein levels in groups segmented by genotype. Similar comparisons will be made between schizophrenic cohorts and normal controls, in a diagnosis by genotype analysis with an ANOVA, or when appropriate an ANCOVA (controlling for variables such as age, race, gender, and postmortem interval).

• Bipolar Disorder
• Depression
• Anxiety Disorders
• Schizophrenia
• Tourette's Syndrome
• Brain Diseases

• Meyer-Lindenberg A, Straub RE, Lipska BK, Verchinski BA, Goldberg T, Callicott JH, Egan MF, Huffaker SS, Mattay VS, Kolachana B, Kleinman JE, Weinberger DR. Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition. J Clin Invest. 2007 Mar;117(3):672-82. Epub 2007 Feb 8.
• Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, Hashimoto R, Harrison PJ, Kleinman JE, Weinberger DR. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5' SNPs associated with the disease. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6747-52. Epub 2006 Apr 17.
• Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Shannon-Weickert C, Akil M, Crook J, Vakkalanka RK, Balkissoon R, Gibbs RA, Kleinman JE, Weinberger DR. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12604-9. Epub 2004 Aug 13.

• INCLUSION CRITERIA:

Brain tissue is needed from individuals suffering from a variety of neuropsychiatric disorders, especially schizophrenia, but also anxiety disorders, suicide, bipolar disorder, depression, Tourette's Syndrome, drug addictions (PCP, cocaine, alcohol, heroin or the like) and any form of dementia. In addition, brains from normal individuals without a history of neuropsychiatric disease will be needed for controls.

EXCLUSION CRITERIA:

No living subjects are enrolled in this protocol. Tissue is obtained after death, with the permission of next of kin, or from existing institutions with appropriate samples via an MTA or other applicable agreement.

Brain tissue is excluded from collection if there is a previously known history of strokes, lesions, or other major neuropathological abnormalities prior to the consenting process.