The NSW Tissue Resource Centre (brain bank) and donor programs: their development and importance for neuropsychiatric research

Since the 1980s, brain ‘archiving’ or ‘banking’ has undergone the greatest social, technological and organizational change in its 200-year history. The NSW Tissue Resource Centre (TRC) was established in 1994 at the Department of Pathology, University of Sydney. The aim of the TRC and linked Australian Brain Donor Programs (ABDP) is to provide human brain tissue for scientific research. The TRC focuses on schizophrenia and allied disorders, alcoholism and motor neuron disease. For the ‘bank’ to be effective, the TRC needs a wide cross section of the population – that is people who have brain disorders as well as people without disorders (controls). Human brain tissues can be collected either through Departments of Forensic Medicine (DOFM) or through premortem donor programs. At the DOFM, on the day of postmortem, we invite the next of kin (NOK) of deceased persons to consider brain donation for research. We have documented NOK responses to the question of brain donation and 62% of them say ‘yes’. We have also reviewed the reasons behind these decisions, which will be discussed. There are several premortem donor programs wherein people sign up during life and donate after death (www.braindonors.org). In 1997, the Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD) established a brain donor program called ‘Gift of Hope’ for people with major psychiatric illnesses. There are 378 registered expressions of interest and 143 donors have completed the enrollment and assessment process. In 2002, the TRC established a program called ‘Using Our Brains’, which targets people without illness (controls). Consented donors have repeat neuropsychological assessments throughout their life with a full health, lifestyle and clinical work up. The comprehensive longitudinal profile that results is extremely useful for researchers using TRC tissues. There are over 2000 registered donors and 331 have had their clinical assessments. Many of our premortem brain donors have completed questionnaires regarding their motivation to donate and this information will be helpful in preparing future promotional activities for both transplantation and research programs. Their neuropsychological assessments have allowed us to derive preliminary normative Australian data on select populations, including those with schizophrenia and alcohol problems. The ABDP also has separate programs for Alzheimer's disease and movement disorders. All donated brains are processed in a standardized manner – one hemisphere is fixed in formalin, the other is frozen at –80°C. A neuropathologist examines all cases and a psychiatric clinician establishes the neuropsychiatric status of the ‘case’, which must meet DSM-IV criteria. The status of ‘control’ cases is reviewed using the same process. A secured research database is used to manage all information in relation to each case. Hence, the TRC can provide fixed and frozen tissues from cases that are well characterized both clinically and pathologically. Researchers must complete a ‘tissue request form’ that outlines the research proposal and identifies their tissue requirements. They must show the scientific validity of the project and their expertise to work with human brain tissue. A scientific board evaluates each request for scientific merit and feasibility prior to approval. Over the past decade, the TRC has collected 445 cases. Tissues have been used for neuropathological, neuropharmacological, immunohistochemical, gene expression and proteomic analyses. Laser capture can be used for microdissection. Tissues have been sent to 108 researchers (84 national and 24 international) for 260 different projects. In 2004/2005, there were 35 research projects compared with a total of 34 projects in the first 5 years. There have been 94 peer-reviewed publications including 34 on neuropsychiatric disorders and 36 on alcohol use disorders. The most popular current research methodologies used by researchers are genomics (37%) and proteomics (31%), which require frozen brain tissue. This is different to the 1994/1999 period where 85% of tissue requests were for neuropathological studies (fixed tissues). The size of tissue samples required has decreased dramatically from blocks of 5–10 g in the 1990s down to 0.1 g of tissue today. Thus, one brain can be used for many different research projects. This increases the value and potential outcomes from each case. Data from different studies on the same cases can be cross-correlated – a value-added outcome. Human brain tissue from the TRC provides an important resource that will become progressively more useful as new techniques such as proteomics and genomics continue to develop and novel antibodies are developed for the further study of neuropsychiatric diseases.