Mechanisms by which exercise promotes hippocampal function in both depressed and non-depressed individuals: A feasibility study

Depression is one of the top ten health problems in the world, affecting millions of Canadians. Research indicates that exercise is an effective treatment for depression but it is not clear on exactly how and why it works. Animal studies show that exercise improves the ability of the brain to function. It can even lead to new cell formation in a part of the brain called the hippocampus, which is important for memory processing. This study is investigating whether exercise may also improve hippocampal function in depressed humans. One way exercise may improve brain function is by normalizing levels of the hormone cortisol, and its toxic effects on the hippocampus. Exercise may also normalize levels of biochemical markers called cytokines involved in inflammation, while improving levels of growth factors important to brain cell function. This feasibility study aimed to develop protocols to investigate changes in hippocampal activity while participants are performing memory tests involving association of images and words in a functional magnetic resonance scanner before and after a 12 week exercise program. It also aimed to develop and validate protocols to measure changes in cortisol, cytokines and growth factors which are likely to be affected by exercise. Our preliminary imaging results revealed hippocampal dysregulation in the depressed brain, and biomarker analysis revealed abnormal concentrations of interleukin-6, vascular endothelial growth factor and salivary cortisol when compared to normal healthy controls. However, following the 12-week exercise program a more normalized pattern of hippocampal activation associated with successful memory encoding was observed. Additionally, biomarker concentrations either resembled or were closer to normal healthy values. Over the long term, the project arising from this feasibility study has the potential to provide a tool to improve exercise prescription, to predict exercise responders and to guide development of combined treatment approaches related to biochemical markers in order to optimize depression outcomes for Canadians