The treatments currently available for bipolar disorder and major depression are effective in relieving symptoms in only about 70 per cent of the patients. Furthermore, some patients have difficulty tolerating the side effects of these medications. In my lab, we are using Positron Emission Tomography (PET) scans to examine the levels of brain chemicals serotonin and dopamine in people with these mood disorders. Serotonin and dopamine control our emotions, sleep, appetite and energy, all of which are altered in patients with mood disorders. We are studying how these brain chemicals are altered and where changes in the brain occur, so we can develop new treatments that target these areas. Our research to date suggests that one type of serotonin receptor may be important in treating depression. In addition, I have set up a Canadian consortium on bipolar disorder (also known as manic depressive illness), which includes experts on bipolar disorder from all major Canadian universities. The consortium has recently received more than $2 million of funding from the Canadian Institutes of Health Research to examine the optimal length of therapy with novel antipsychotics and the effectiveness of psychotherapy and psychoeducation. We will also be pooling resources to examine how people with bipolar disorder respond to existing treatments compared to their outcomes with new treatments. We will be able to gather extensive data from all the sites to assess the effectiveness of different therapies. Given that many patients with bipolar disorder have problems with memory and concentration, we will study whether these symptoms are part of the illness and if early treatment can diminish them. My goal is to discover what brings on these symptoms and develop new treatments that improve patient outcomes and quality of life.
Research Pillar: Clinical
Investigation of the apolipoprotein C-II activation site of human lipoprotein lipase
The enzymes hepatic lipase (HL) and lipoprotein lipase (LPL) play a key role in the metabolism of cholesterol and fat circulating in the blood stream. However, their specific role and capacity to offer protection from heart disease are unclear. My research will identify the parts of each enzyme responsible for performing different functions. This knowledge will more clearly define how these enzymes influence the metabolism of cholesterol and fat and the development of cardiovascular disease. I am combining parts of HL and LPL to create new enzymes that will highlight the differences between the original enzymes’ functions. For example, a fundamental property of enzymes is how they are activated. We know a particular protein that does not activate HL does activate LPL. I will put the portions of LPL we think are responsible for activation into HL to test whether HL is activated and confirm that this part of LPL causes activation. When we know how these enzymes work to regulate and control the level of cholesterol and fat, we will understand their relationship with cardiovascular disease, and should be able to develop enzyme inhibitors or activators to improve cardiovascular health.
Early labour support at home: an RCT of nurse visits and telephone triage
Cesarean section rates have been considered too high in North America for a number of years, and the rate appears to be rising. My research will assess whether a different approach to early labour care lowers the rate and is cost-effective. Currently, women who phone British Columbia’s Women’s Hospital and Health Centre in labour, wondering whether they should come in to the hospital, receive telephone advice only. My research study will focus on women having their first baby who call the hospital for advice. Women who agree to participate in the study will be randomly assigned either the current method of telephone care or a visit from a delivery suite nurse, who will conduct an assessment in the woman’s home. This is the same assessment that takes place when women arrive at the hospital. The nurse will call the woman’s physician from her home, and the three of them will plan what to do next. In this study, I will compare the outcomes of home visits to telephone advice to determine whether the cesarean rate is lowered. We anticipate that early labour support and assessment at home will enable women to delay admission to hospital until labour is well established, reducing the use of cesarean sections and other interventions. We know from a small pilot project that babies seemed less likely to have problems at birth with this approach to maternity care. In addition, we will compare the cost of the two methods. We expect early labour support at home to reduce the costs associated with cesarean section and longer hospital stays.
Aminophylline bolus in bradyasystolic cardiac arrest: a randomized placebo-controlled trial
Cardiac arrest occurs when the heart stops pumping blood effectively. Without blood flow, no oxygen circulates and brain damage can occur within minutes. Bradyasystole, a type of cardiac arrest where the heart beats very slowly or not at all, accounts for more than half of cardiac arrests. Less than three out of every 100 people who experience this type of cardiac arrest survive. Bradyasystolic cardiac arrest may be caused or worsened by adenosine, a chemical that exists in our bodies and is released by cells when the heart is under stress. The drug aminophylline has been used to treat asthma for years, and may also counteract the adverse effects of adenosine during cardiac arrest. My research will evaluate the effectiveness of aminophylline in improving survival from bradyasystolic cardiac arrest. All advanced life support ambulances in Greater Vancouver and Chilliwack are participating in this double-blind, randomized study. Patients will receive either aminophylline or a placebo in addition to standard resuscitative care. The patient, paramedics, physicians and nurses will not know what the patient received. If the therapy proves beneficial, numerous lives could be saved. About 1,000 people experience cardiac arrest in North America every day, and the majority would be eligible for this treatment.
Bone Health in Adult Women: The Relevance of Dietary Restraint, Cortisol Excretion and Nutrition-Related Stress
Candice Rideout is fascinated with bones. Despite a perception that bones are static once we’re fully grown, they’re actually ever-changing, which intrigues Candice. She is also interested in how nutritional behaviours affect bone health. The two interests come together in her research. Candice, who transferred from a Masters to PhD program, is examining bone health in adult women, looking specifically at possible links between dietary restraint, stress and bone density. The first phase of the research involved a broad survey of more than 1000 healthy postmenopausal women. Phase II will be an intensive study of a sub-group of women from the first phase, in which Candice will investigate the hypothesis that high levels of dietary restraint (the perception that one is constantly monitoring and attempting to limit food intake in an effort to achieve or maintain a desired weight) is associated with increased stress and possibly lower bone density. The diet and physical health of Phase II participants will be studied over a three-month period. Candice hopes this research will contribute to a better understanding of how nutritional factors relate to women’s health and wellbeing.
Neurocognition, movement disorder and corticostriatal function in first-episode schizophrenia
For people living with schizophrenia, anti-psychotic medications can help control delusions and hallucinations. However, it is far more difficult to treat schizophrenia’s neurocognitive effects, such as disordered thinking and problems with memory and planning. Dr. Donna Lang is working toward uncovering the underlying causes of these devastating symptoms. Her previous research included a study comparing risperidone – a new-generation drug – to traditional anti-psychotics, in terms of how they affect deep-brain structures called the basal ganglia. Lang focused on how faulty wiring between the basal ganglia and other brain regions may be linked to neurocognitive problems in people with schizophrenia. In her current study, Lang is using tools such as Diffusion Tensor Imaging – state-of-the-art imaging technology – to learn more about brain activity in schizophrenia patients, before and after treatment. Lang hopes findings from the research will lead to more effective treatment of schizophrenia.
Dietary lipids in growth, development and health
My research focuses on the role of dietary fat in providing essential fatty acids to support growth and development, including long-term effects on children’s physical, cognitive and behavioural health. I am investigating how specific fatty acids influence brain development and nerve function, the dietary intakes needed to ensure optimal development, and the role of altered fatty acids in disorders such as liver disease and cystic fibrosis. Clinical applications of this research have ranged from developing special feeds to support optimal brain development in premature infants, to research into diets for prevention of seizures and liver damage in children with cystic fibrosis. I also head a nationally funded Nutritional Research Program exploring how our genetic makeup blends with our nutritional intake, particularly in the maternal and early childhood period, to affect our life-long susceptibility to disease. Findings will provide important new information about tailoring nutritional intake to meet individual needs in health and disease.