Abstract
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.