Project Summary

Flora Vaccarino, M.D. (Independent Investigator 2003) of Yale University, will investigate hippocampal atrophy in depression, as this occurs in the brain of people with depression. However, it is not known if the cell loss is secondary to depressive symptoms or a primary cause of the symptoms. She hypothesizes that the hippocampus normally protects against affective disorders by a beneficial down-regulation of the hypothalamic HPA axis and interactions with the prefrontal cortex, thus predicting that a primary disturbance in hippocampal growth would cause a dysregulation of mood and affect and abnormal responses to stress. She will test this using mice she generated which have hippocampal atrophy because of a mutation of a Fibroblast Growth Receptor, Fgfr-1, which is important for the proliferation of hippocampal progenitor cells (the mice show reduced hippocampal growth since infancy). Dr. Vaccarino will investigate the degree of impairment in hippocampal neurogenesis (regrowth of cells) in regular conditions and whether age modulates this phenomenon; she will assess levels of anxiety and depression, following which hippocampal neurogenesis will be assessed; and she will assess depression as a helpless response to repeated stress. She believes that decreased hippocampal growth will cause impaired affective regulation in these mice and will make them more vulnerable to the deleterious consequences of stress. Consequently, she expects to find less neurogenesis occurring in these mice as a result of greater stress.

Program Area: MOOD DISORDERS\Bipolar

Search Again