IDENTIFICATION
OF THE GENE(S) RESPONSIBLE FOR OR INVOLVED IN BIPOLAR AFFECTIVE DISORDERS
The aim of this research is to identify polymorphisms in DNA which are associated with bipolar affective disorders and subsequently isolate the responsible gene(s). We have performed linkage analyses within large families and have located a susceptibility locus on chromosome 12. We are now developing a diagnostic test and attempting to isolate the causative gene(s).
DEVELOPMENT OF TRANSGENIC ANIMALS AS MODELS FOR THE STUDY OF AFFECTIVE DISORDERS
We have developed a line of transgenic mice with altered hypothalamic-pituitary adrenocortical (HPA) systems. This model allows for the expression of a glucocortical receptor (GR) antisense RNA in the brain. This animal model should help us to determine the neuroendocrinological mechanisms involved in affective disorders and analyze the mode of action of antidepressant drugs.
ROLE OF CORTICOSTEROID RECEPTORS IN THE REGULATION OF THE HPA SYSTEM BY ANTIDEPRESSANTS
Our work has also shown that different types of antidepressants can alter GR mRNA levels and increase GR gene expression in a time frame that closely follows improvements seen in clinical depression. This work brings new insights in the mode of action of antidepressant drugs and suggests a line of approach in the development of new drugs.
These projects are supported by the Medical Research Council of Canada and the Fonds de la recherche en santé du Québec.
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