Research Pillar: Clinical

Depression is a widespread mental illness, affecting one in ten people. Twice as many women as men suffer major depression. Hormonal changes brought on by puberty, menstruation, menopause, and pregnancy may contribute to the higher risk, as these periods in a woman’s reproductive cycle have been associated with depression. Hormone replacement therapy has been prescribed to treat changing sex hormone levels, but a study found the health risks exceeded the benefits. Carolin Klein is investigating the impact of an alternative approach, cognitive-behavioural therapy (CBT), on hormone levels. CBT has been as effective as medication in treating depression, with no side effects. If depression and sex hormone levels are related, cognitive-behavioural therapy could also normalize hormone levels. Carolin is measuring hormones in depressed men and women before, during, and after CBT. The results could clarify if changing hormone levels cause depression, and lead to greater use of cognitive-behavioural therapy to treat abnormal hormone levels, without the side effects associated with some medications.

The placebo effect, when a patient’s beliefs or expectations can influence the course and outcome of disease, is a well-recognized medical phenomenon that is particularly prominent in neurological disorders such as depression, pain and Parkinson’s Disease. But little research to date has examined the therapeutic impact of taking placebos and the mechanism by which they work. Studying the placebo effect is also important to assess the need to control the phenomenon in clinical trials, and to address the difficulty in detecting a true therapeutic effect when benefits are masked by a strong placebo effect. Sarah Lidstone is using advanced imaging techniques to assess the physiological changes in the brain associated with the placebo effect in Parkinson’s Disease. Sarah is studying how a patient’s expectation about their treatment influences how they respond to that treatment. Her group has already discovered that a placebo can induce the release of dopamine in the brains of Parkinson’s patients. A deficiency of dopamine, a chemical that transmits messages between brain cells involved in controlling movement, causes Parkinson’s Disease. The research could help explain how the placebo effect occurs in Parkinson’s, and improve treatment for the disease, along with drug addiction, depression and pain.

Valproic acid is an anticonvulsant drug frequently prescribed to epileptic patients, and also used to manage bipolar disorder, migraine headaches and pain. Despite its ability to control seizures, the drug is associated with a rare, but potentially fatal liver toxicity. It is unclear how valproic acid causes liver failure, and health care professionals are unable to predict which patients will be affected, although it occurs more frequently in patients younger than two years of age who are also taking other anticonvulsant medications. Tony Kiang is researching the factors that cause and the mechanisms responsible for valproic acid induced liver failure in pediatric epileptic patients. The research could help physicians identify patients at risk of liver toxicity before prescribing valproic acid, so other medications can be used instead. The findings could also be applied to other drugs with similar side effects to improve their safety, and to identify compounds likely to cause side effects during drug development.

Hypertension (high blood pressure) is a major public health issue. About 22 per cent of Canadians have hypertension, a risk factor for numerous cardiovascular diseases, including stroke, coronary heart disease, kidney failure and narrowing of the blood vessels to the arms, legs and feet. Jessica Scott is examining the effects of exercise in people with mild or moderate hypertension. Previous studies have shown an eight to 10-week physical exercise program can dramatically reduce blood pressure in hypertensive individuals. But the striking decrease in blood pressure immediately following exercise may be dangerous for these patients. While standing, gravity displaces blood away from the middle region of the body and pools in the extremities, reducing the volume of blood available to the heart. Fainting after exercise as a result of this pooling in the extremities may be the first indication of a serious cardiovascular condition. Jessica is investigating whether a sudden drop in blood pressure predisposes people with hypertension to lose consciousness following exercise. Ultimately, she aims to develop a safer, more effective exercise program for people with high blood pressure.

The heart pumps oxygen-rich blood throughout the body. Because a limited volume of blood circulates, the body must decide how to distribute the available blood. Research indicates that during intense exercise, the respiratory muscles begin to demand a greater proportion of the total blood flow thus limiting the blood available to the other exercising musces of the body. In healthy people, strenuous exercise fatigues the diaphragm, the primary muscle that controls breathing. Jonathan Witt is studying whether daily training sessions to strengthen breathing capacity will improve the diaphragm’s efficiency, reduce the amount of blood required when breathing harder, and improve blood flow to the legs. The findings could help patients with chronic obstructive pulmonary disorder (COPD) and cystic fibrosis, whose breathing muscles are overworked, and those with chronic heart failure, who pump even less blood from the heart. The research could lead to new therapies to improve strength and functional capacity in these patients.

Eighty percent of spinal cord injuries happen to people under 30 years of age. Medical advances have increased life expectancy for these individuals, and consequently, they are susceptible to the same chronic conditions as able-bodied persons. However, people with spinal cord injuries have a much higher risk for cardiovascular disease. About 25 percent of the general population has a form of cardiovascular disease, but 60 to 70 percent of people with spinal cord injuries have a form of the disease. Physical inactivity is a major risk factor for cardiovascular disease, and people with spinal cord injury are often inactive and have poor cardiovascular fitness. Dominik Zbogar is investigating whether an arm cycling training program could improve aerobic fitness, heart function, muscle function, vascular (blood vessel) health, and psychological well-being in people with spinal cord injuries. This research could clarify the importance of exercise rehabilitation to overall health and quality of life for people with spinal cord injuries, and contribute to prevention and treatment of cardiovascular disease.

Exposure to high altitude can have adverse physiological effects, including altitude illness and decreased occupational and athletic performance. People can acclimatize to high altitude by making a gradual ascent and taking certain medications, but these drugs can have negative side effects, and gradual ascent is not always possible. Dr. Michael Koehle is researching whether daily exposure to intermittent hypoxia (low oxygen gas) could potentially reduce altitude illness and improve exercise performance at higher altitudes. Intermittent hypoxia is a commercially available treatment that has been shown to increase breathing capacity at rest after six days of the treatment. However, the treatment’s risks and benefits are poorly understood, and its effects on breathing during exercise are unknown. Michael is studying how intermittent hypoxia affects breathing in healthy individuals during rest and exercise. The results could be used to determine the most effective protocol for increasing breathing capacity, and could indicate the optimal dose for preventing altitude illness. The research may also have clinical applications for treating other conditions such as sleep apnea, when repetitive pauses in breathing occur during sleep.