Project Summary

Michael J. Meaney, Ph.D. (Distinguished Investigator 2002) of Douglas Hospital Research Centre, is interested in the mechanisms by which adversity in early life might alter neural development so as to render certain individuals at risk for pathology later in life.  Early life events serve as potent determinants of vulnerability/resistance to chronic illness, including depression, anxiety disorders, schizophrenia, and drug abuse.  He and others have proposed that a link between the quality of early life and risk for illness lies in the development of individual differences in neural systems that regulate behavioral and endocrine response to stress, notably central corticotropin-releasing factor (CRF) systems.  Interestingly, enhanced CRF activity has been implicated in multiple forms of psychopathology.  Dr. Meaney's focus is on the regulation of hippocampal glucocorticoid receptor (GR) gene expression.  In previous studies, he found that the effects on maternal care appear to be mediated by increased serotonergic activity at the level of the hippocampus; an effect that is mediated by the 5-HT7 receptor and the subsequent activation of camp and PKA systems.  Each of these systems has been implicated using both in vivo and in vitro techniques.  Dr. Meaney hypothesizes that activation of 5-HT inputs increases in NGFI-A expression, increasing the binding of these transcription factors to DNA sites and altering the methylation during this phase. 

Program Area: MOOD DISORDERS\Mood Disorders (General)

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