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Some people manage to trudge through the slough of despond to the other side, while others become mired and never escape. For researchers at the Douglas Hospital, the reason some who are genetically vulnerable to depression survive relatively unscathed while others suffer lies in a complex interplay between genetic and environmental factors. Thanks to the creation of the new Neurophenotyping Centre at the Douglas Hospital Research Centre, untangling the relations between nature and nurture should become easier.
Neurophenotyping involves looking at the environmental effects on the expression of vulnerability genes - that is, how the environment turns on and off certain genetic processes. "For mental illnesses such as depression, schizophrenia, and Alzheimer's disease, a number of vulnerability factors have been identified - that is, specific features of genes that have been identified as possible participants in the onset or development of disease," says Claire-Dominique Walker, director of the Neuroscience Research Division at the Douglas Hospital Research Centre, and also the director of the Neurophenotyping Centre. "The new centre will focus on how changes in the environment - including the air you breathe and the food you eat, as well as social interaction - influence how your genes are expressed."
Such research exists at the cutting edge of brain science and the new facility will enable scientists to coordinate socio-behavioral and genetic research. The centre, at more than 15,000 square feet, will include a semi-natural environment for test animals, so that instead of living in little cages, lab rats will have large enclosures in which to develop social bonds and hierarchies. "This environment will allow us to modify the way a social hierarchy is established, for example, thus changing social relations and helping us to determine how they and other environmental factors will affect the expression of vulnerability genes in these animals," says Walker. In addition to these larger and more specialized animal facilities, the new centre will also have behavioural analysis laboratories and rooms for tissue analysis and genetic processing, enabling researchers to track genetic expression in coordination with environmental change. The facility could become a state-of-the-art research home for up to 60 researchers and 180 graduate students and post-doctoral fellows.
The centre's impact extends beyond animal research. "Our work here will be the initial step toward increasing our understanding of human vulnerability in different environments," says Walker. As Rémi Quirion, scientific director for the Douglas Hospital Research Centre, notes, "Work at the centre will directly benefit patients. For example, many of our researchers are interested in the role of genetics in drug response. We will be able to evaluate why some medications work better for some patients. This will ultimately lead to patient-tailored drug regimes and overall better treatment of disease."
Walker's research focuses on the early development of neurotransmitter systems, which are important in diseases like depression and schizophrenia. As rodents are not as mature as humans at birth, researchers can study a period of brain development similar to that in the last stages of pregnancy in humans. "I've always been intrigued by stress and development. I'm interested in how an enriched environment, even after weaning, can actually address and repair the negative effects of prenatal stress," she says. Walker's research is also contributing to the Maternal Adversity, Vulnerability and Neurodevelopment project directed by another Douglas researcher, Michael Meaney, which has received $4 million from the Canadian Institutes of Health Research. Walker and a University of Toronto colleague coordinate the animal component of the project, while other researchers are working with human participants.
The Neurophenotyping Centre will be the only one in Quebec, thus drawing researchers from around the province. The Centre will receive $5 million from the Quebec Ministry of Economic Development, Innovation and Export, and $1 million from the Douglas Hospital Foundation. Construction is scheduled to begin in fall, 2007.