Osteoarthritis occurs when cartilage (the gristle that lines the ends of the bones) is damaged. It is the most common form of hip arthritis and is responsible for more than 90 percent of hip replacements. Recently, subtle deformities of the hip have been linked to hip osteoarthritis, and it is now believed that these deformities, combined with certain types of physical activities, such as hockey, soccer and bicycling, are one of the major causes of damage to the hip. Since the deformities have been observed in young adults, it may be possible to detect and treat osteoarthritis at an earlier stage, or prevent its development. Dr. Chuck Ratzlaff’s research will demonstrate how physical activity and one or more subtle deformities of the hip can cause cartilage damage and eventually osteoarthritis. He will determine the frequency of deformities in the Caucasian population in comparison to the Chinese population, which is thought to have a lower frequency of osteoarthritis. He will also determine how physical activity over one’s lifetime contributes to osteoarthritis. For this study, participants with and without hip pain from both Caucasian and Chinese populations will attend a two-hour assessment session consisting of a physical examination, a hip x-ray, and a questionnaire on physical activity. He will use new magnetic resonance imaging (MRI) techniques to see how the physical motion and the deformity combine to damage cartilage. This research program will generate the new knowledge needed for major breakthroughs in the prevention, detection and treatment of hip osteoarthritis. Given an aging population and the increased prevalence of chronic diseases in Canada, physical activity is an important intervention for health. Knowledge of how to modify and perform physical activities, and identification of susceptible individuals, will lead to inexpensive and practical recommendations that maximize the benefits of physical activity without increasing the risks of joint disease. It may also lead to identification of a subset of people that will benefit from minor hip surgery to correct the subtle deformity, thus preventing the later development of hip osteoarthritis and its associated burden of suffering and other costs to the individual and society.
Research Pillar: Clinical
Exercise Intensity Prescription in Breast Cancer Patients Undergoing Chemotherapy Treatment
Most people today know someone affected by breast cancer. The statistics are startling, one in nine women is expected to develop breast cancer during her lifetime, but thanks to modern therapies, including chemotherapy, only one in 28 is expected to die from it, and many women go on to have a normal life expectancy. Chemotherapy , while effective, is associated with many negative short-term side effects. Importantly, exercise programs during chemotherapy provide a beneficial influence on many of the treatment-related side effects, but the specific parameters of exercise associated with optimal benefits remain unclear. Furthermore, studies of chemotherapy and exercise use a method of exercise intensity prescription that does not account for chemotherapy side effects: often, the prescription will be based on the body's response to exercise prior to chemotherapy treatment. Amy Kirkham is undertaking research to provide information on how the body changes with respect to exercise ability throughout chemotherapy treatment – information that is not currently available. Specifically, she will frequently test indicators of physical fitness in a group of breast cancer patients who are participating in an exercise and chemotherapy study, to analyze and compare the changes between tests and over time. Additionally, she will try to develop and validate a simple exercise test that can be used easily and often to adjust the exercise intensity prescription of breast cancer patients currently involved in a chemotherapy and exercise study. The results of Ms. Kirkham’s research could lead to the development of a more accurate method for prescribing exercise for cancer patients, and ultimately affect how other research on cancer and exercise is conducted in the future.
The effect of hyperoxia on baroreflex function in patients with sleep apnea
Obstructive sleep apnea (OSA), is a condition characterized by several stops and starts in breathing during sleep. This is caused by the collapse and re-opening of throat muscles. Unfortunately, the estimated one in four men and one in ten women who suffer from this condition are four times more likely to suffer from a stroke. The reasons for this phenomenon are not clear; however one likely explanation is an impaired ability among people with OSA to maintain normal blood pressure. In healthy individuals, when blood pressure increases the body reacts with a series of processes in order to bring blood pressure back down to normal levels. These processes are collectively called the baroreflex. However, the baroreflex is impaired in people with OSA, which results in dangerously high blood pressure and consequently, an increased risk for stroke. To-date, research has shown that baroreflex function is not only a powerful predictor of stroke, but also has strong prognostic value following a stroke. Indirect suggestions have been made of a potential improvement of the baroreflex in healthy humans when breathing supplemental oxygen (i.e. breathing high levels of oxygen). However, this remains to be investigated in people with OSA. In what is the first study to evaluate the effectiveness of supplemental oxygen in improving the baroreflex function in OSA, Jordan Querido is evaluating cardoirespiratory variables, including ventilated oxygen and carbon dioxide levels, sympathetic outflow, blood pressure, stroke volume, and heart rate, in both OSA patients and a group of healthy controls. Additionally, he will investigate the mechanisms which place OSA patients at greater risk for stroke, thereby potentially reducing their risk of stroke, and improving the prognosis following stroke.
Assessing Protective Factors for Self-harm: Development of the Barriers to Self-harm Inventory
Deliberate self-harm (DSH) is the deliberate, direct destruction of body tissue without suicidal intent. Common forms of DSH include cutting, burning or hitting oneself and, not surprisingly, it is associated with a variety of negative health outcomes. DSH often begins in adolescence. Without treatment it can persist for several years and decades. Although promising treatments exist, studies indicate that many individuals in treatment fail to reduce their DHS behaviours. To date, few studies have examined factors that directly prevent someone from engaging in DSH, either over the short- or long-term. Brianna Turner’s research is focusing on factors that directly prevent DSH, as well as the development of a novel psychometric measure that can be used easily within busy health care settings to assess protective barriers against DSH and predict future DSH. These are novel research directions that fit within two larger investigational projects underway that looking at the emotional, individual and environmental factors that predict changes related to self harm. Additionally, and importantly, the results of this study have the potential to improve the quality of care and health outcomes for individuals who engage in deliberate self-harm.
Visual-spatial attention and falls risk in seniors: Do fallers show impairments in reflexive orienting?
Seniors who fall and sustain injuries or worse, injury-related deaths, represent a major health concern. Approximately one-third of seniors over the age of 65 experience one or more falls per year, 20 percent of which require medical attention. In Canada, falls result in over $2.4 billion annually in direct health care costs. A growing body of research suggests that cognitive factors, such as visual-spatial attention, play a major role in a person's risk for falling.
In an earlier study, Lindsay Nagamatsu found that seniors who are prone to falling (fallers), may be less likely or slower to notice hazards while navigating within their environment. In other words, fallers appear to have a narrowed focus of attention compared to non-fallers. This may cause them to overlook hazards or obstacles and prevent them from safely navigating the immediate environment, and avoid falling. Failing to notice a step or a curb, for example, may lead to a fall.
In this, her second, follow-up study, Ms. Nagamatsu will determine whether other aspects of attention are also related to falls. Her research focuses on examining automatic attention in senior fallers through a series of carefully designed experiments. Identifying the causes of falls in seniors is important because success will guide strategic interventions to prevent falls and consequently reduce individuals' injuries and societal health care costs. The results of this study could also be applied to develop novel risk screening strategies for fallers.
Neural Mechanisms of Reward Learning and Cognitive Control in Children with Attention Deficit Hyperactivity Disorder
Attention Deficit Hyperactivity Disorder (ADHD), is characterized by its behavioural manifestations including difficulties with attention, hyperactivity and impulsivity. It is one of the most common childhood disorders with a prevalence rate of three to seven percent of school-aged children. ADHD carries a significant impact not only on children diagnosed with this disorder, but also on their families, schools, communities and the health care system. Numerous theories of ADHD have focused on deficits in executive functions, specifically cognitive control and the inability to inhibit inappropriate behaviours. Neuropsychological and neuroimaging studies in children with ADHD support a theory of frontal-subcortical dysfunction: specifically, a dysfunction in the midbrain dopamine (DA) system that may result in an impaired midbrain DA system and reinforcement learning, or the ability to learn to modify behaviour on the basis of rewarding and punishing stimuli in the environment. Furthermore, recent developments in reinforcement learning theory indicate that the midbrain DA system carries Reward Prediction Error (RPE) signals. Carmen Lukie is investigating how a midbrain DA system for reinforcement learning may be impaired in children with ADHD. This study follows on from her earlier research which showed that children with ADHD are particularly sensitive to the saliency of rewards. Specifically, she found that RPE signals in children with ADHD are modulated by the context in which feedback is given, and differs from what is observed in typically developing children. The current study will replicate this finding, while correcting for the limitations of the earlier study. Ultimately, the results of this research could lead to the development of novel, more effective behavioural and pharmacological treatments. Further, the research may expand to include individuals with substance abuse, pathological gambling, conduct and borderline personality disorders.
The Positive Illusory Bias (PIB) in parents with and without Attention-Deficit/Hyperactivity Disorder (ADHD)
Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychological conditions in childhood. This disorder is characterized by inattentiveness and/or hyperactivity or impulsivity. Children with ADHD can have major difficulties in important areas of their life, such as in relationships, in their family, and at school. In addition, although treatments are available for this disorder, none of the treatments are without problems and they are of limited long-term effectiveness. Recent studies show that adults can also have ADHD. These adults are at risk for conduct problems, substance abuse, relationship difficulties, driving impairments, employment issues, academic deficits, and poor parenting. Thus, ADHD has negative consequences for both the individual and society. However, as with children, much remains to be done to improve the success of treatments for adults with ADHD. Children with ADHD overestimate their abilities in areas in which they are actually deficient. This is called a Positive Illusory Bias. It is well-known that children are typically optimistic, but the bias of children with ADHD is different from this normal optimism in three major ways. First of all, children with ADHD have a greater absolute positive bias than children without ADHD in that their self-perceptions are even more positive than the self-perceptions of children without ADHD. Secondly, in contrast to those without ADHD, the positive illusions of children with ADHD do not serve to enhance the children’s motivation, endurance, or performance. Finally, children with ADHD maintain their positive illusions even in the face of clear contradictory evidence while the positive illusions of those without ADHD move closer to reality after receiving feedback. Clearly, the Positive Illusory Bias found in children with ADHD is qualitatively different than the self-enhancing optimism generally found in children, and it may have detrimental consequences for the performance of these children and for their motivation to engage in treatment. To date, no research explores the existence of the Positive Illusory Bias in adults with ADHD. In particular, no studies have tested whether the Positive Illusory Bias found in children with ADHD also exists in parents with ADHD. Given research showing that children with ADHD are likely to have parents with ADHD, it seems crucial to examine this question. If a Positive Illusory Bias does indeed exist in parents with ADHD, then these adults may have less motivation to seek or maintain treatment for managing both themselves and their children. For instance, if adults with ADHD hold overly positive views of their parenting, they will be less likely to use parenting programs and services. This could have a negative effect on the outcome of their children. My research will test whether parents with ADHD have a Positive Illusory Bias in the areas of work, relationships, intelligence, and parenting. Female participants who are mothers will be recruited into two groups: a group of mothers with ADHD, and a control group of mothers without ADHD. The diagnosis of ADHD will be determined by information provided by the participant and by someone who knows the participant well (e.g. a spouse). All mothers will complete a self-perception questionnaire that inquires about the four previously-mentioned domains of functioning. The other informants (those who know the mother well) will complete the same questionnaire, answering the questions in reference to the mother. The ratings of the other informants will then be compared to the self-ratings of the mothers. It is predicted that differences in discrepancies between self and other ratings will be larger in the ADHD group than the control group. I will also assess whether the mother is depressed, whether her child has ADHD, and whether the mother has a tendency to respond in a socially desirable manner, so that these variables can be controlled for in analyses of the discrepancy scores. Knowing whether a Positive Illusory Bias exists in adults and more specifically, parents with ADHD can lead to improvements in relevant treatments. For instance, this Positive Illusory Bias may contribute to treatment resistance, whether the treatment is ultimately for the adult or for their child, and it may be possible to develop and utilize specialized techniques to bring the positive self-perceptions of parents with ADHD more in line with reality before beginning treatment. Moreover, consideration of the Positive Illusory Bias as a predictor of treatment response will allow for more informed problem-solving on the part of the clinician in response to resistance to treatment from the client. As such, although there are a number of ways in which the Positive Illusory Bias in parents with ADHD may contribute to improved treatment for this disorder, it is necessary to first answer the question of this study, which is whether or not this bias exists in parents with ADHD.
Identifying biomarkers associated with the diagnosis and illness progression of mood disorders
Despite decades of extensive genetic and pharmacological research, the pathophysiology of Bipolar disorder (BD) remains elusive. Consequently, a growing number of studies are focusing on the molecular biology underlying BD, and some consistencies with respect to possible mechanisms of action have emerged, including: (1) altered cerebral energy metabolism; (2) decreased expression of the mitochondrial electron transport chain (mETC), complexes I-V subunits in prefrontal cortex, hippocampus and lymphocytes; (3) increased protein oxidation in the prefrontal cortex and serum; (4) higher levels of lipid peroxidation in the cingulte cortex and serum; (5) increased levels of DNA oxidative damage in hippocampus and lymphocytes; (6) alteration in the balance between anti-inflammatory/ pro-inflammatory cytokines; and (7) decreased levels of brain derived neurotrophic factor (BDNF) in the hippocampus and serum. These findings highlight the fact that oxidative damage and neurotrophic factors are present in both the brain and periphery, and suggest that oxidative stress and BDNF could be potential biomarkers for mood disorder. Dr. Ana Andreazza is working as part of a collaborative network in Canada, Brazil, Australia and Portugal, that is studying a large sample size of patients with mood disorders (bipolar disorder and depression), in order to determine whether mitochondrial dysfunction, oxidative stress markers, cytokines and BDNF levels may be used as biomarkers of progressive illness. As a secondary objective of their studies, Dr. Andreazza and colleagues will correlate their findings on the oxidative stress with cognitive impairment, accelerated aging (i.e. telomere shortening), and decreased levels of neurotrophic factors. In addition to identifying biomarkers that may be used to follow progressive illness, the results of this work may represent significant therapeutic targets. In the larger picture, the discovery of biomarkers for mood disorders and their incorporation into clinical decision-making could dramatically change the future of mental health care.
Mind Wandering in Individuals with Schizotypal Personality Traits
Disruption of attention is a hallmark symptom of schizophrenia, and it has been shown that people with schizophrenia exhibit reduced levels of sensitivity in processing external stimuli. However, it has also been suggested that healthy individuals do not process external stimuli when they are ‘mind wandering’ to the extent that they normally would when they are paying attention to the task-at hand. That schizophrenia and mind wandering both involve reduced sensitivity to ongoing events in the external world suggests they may be closely related. Therefore, it is possible that the processing deficits associated with schizophrenia are related to levels of mind wandering. Julia Kam is investigating mind wandering states in healthy individuals who may be vulnerable to developing schizophrenia with the purpose of determining whether abnormal levels of mind wandering are consistently evident across the entire spectrum of disorders in which schizophrenia is present. A key implication of this study is that varying levels of mind wandering and the brain wave counterparts observed in the general population may be considered as indicators for the potential development of schizophrenia. Given that schizophrenia has a strong genetic component, these ‘indicators’ may serve to identify healthy individuals, especially relatives of patients with schizophrenia, who are themselves at higher risk for developing the disorder. This is an important first step in implementing preventive interventions for such high-risk individuals. Once identified, persons considered at-risk may then benefit substantially from programs that highlight protective factors and increase awareness of risk factors, all of which are intended to prevent the development of schizophrenia.
Magnetoencephalographic (MEG) investigation of cortical processing in children born very preterm
Children born very preterm (less than 32 weeks from conception), commonly have difficulties with learning and attention that frequently lead to problems in their academic performance. Very little is known, however, about how the brain activity of very preterm children differs from that of children born at full term. Currently, it is known that children born very preterm experience considerable pain-related stress during lengthy hospitalization following birth. This stress is associated with higher levels of cortisol production, the primary stress hormone in humans, during infancy and toddlerhood. It is possible that these high cortisol levels may contribute to changes in brain development. Dr. Sam Doesburg is characterizing alterations in brain function and structure in a group of very preterm children, now aged 7.5 years. His research is part of a larger, ongoing longitudinal study investigating the effects of pain-related stress experienced during neonatal intensive care on neurodevelopment in very preterm children. Using a technique called magnetoencephalography (MEG), Dr. Doesburg will examine the brain activity of the children while they perform a visual memory task, and use magnetic resonance imaging (MRI) to map brain activity onto brain structure to investigate connections between different brain regions. This research will provide new knowledge about brain function and structure in very preterm children, and how stress experienced very early in life is related to brain development. Determining specific information about brain activity in these children during mental activity could also help to devise better treatment strategies to help overcome the learning and attention difficulties this vulnerable group of children experience.