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.
Year: 2009
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.
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.
Functional characterization of T cells and T regulatory cells in Inflammatory Bowel Disease
Crohn's disease and ulcerative colitis, two forms of Inflammatory Bowel Disease (IBD), are disorders believed to be caused by the cells of the immune system mistakenly attacking the tissues of the digestive tract. This phenomenon, known as autoimmunity, leads to massive inflammation of the affected area and consequently causes severe pain, diarrhea, bleeding and other debilitating symptoms. With few treatments and no cure to date, this disease continues to impact both the general population and our health care system. Current research suggests that the inflammation associated with IBD is caused by self-reactive immune cells called T cells that attack the gut tissue, along with a loss of T regulatory cells (Tregs), which act to 'turn off' the immune system. Furthermore, flagellin, a protein present on all motile bacteria including the microflora found within the intestine, may also contribute to the establishment of IBD associated inflammation through its influence on T cells and Tregs. Indeed, studies have shown an immune response is generated against flagellin in 50 percent of patients with Crohn’s disease. However, the nature of these responses remain largely uncharacterized. Megan Himmel's research aims to optimize a novel method of identifying T cells and Tregs which are specifically reactive to flagellin, in order to study their function and their possible contribution to the pathogenesis of IBD. This work may lead to a novel diagnostic marker for IBD, as well as further insight into the immune mechanisms contributing to this disease. Furthermore, Ms. Himmel’s research will provide important insight into the overall role of T cells and Tregs in the establishment and progression of IBD in humans, with the ultimate goal of establishing methods to therapeutically manipulate the balance of pathogenic versus regulatory immune responses.
Measuring equity in the use and financing of prescription medicines
The use of prescription drugs outside of hospitals is not addressed in the Canada Health Act or by any legislation that would ensure national standards for accessibility. As a result, public pharmaceutical insurance programs designed to provide access to prescription medicines outside of hospitals have evolved independently in each province and territory. In May 2003, BC instituted Fair PharmaCare, an income-based catastrophic drug coverage program which links individuals’ private financial contributions to the costs of their medicines (either out-of-pocket or through their private insurance), with their household income. Current research suggests that the implementation of income-based drug coverage has shifted the financial burden away from public sources toward private ones, which raises several important questions regarding equity. Using data from three comprehensive, population-level health care databases, namely: 1) the BC PharmaNet; 2) the British Columbia Linked Health Database (BCLHD); and 3) Fair Pharmacare registration files, Ms. Hanley is investigating the degree of income-related inequity in medicine use before and after the BC policy change in the general population, and in specific subpopulations (e.g., drug use after myocardial infarction). The analysis of specific subpopulations will allow for evaluation of the use of essential medicines and of medications known to be safe and effective. Further, it will enable greater needs standardization. Additionally, she is evaluating the redistributive effect of the policy change on income distribution in BC, specifically focusing on determining inequity in pharmaceutical financing among individuals of equivalent incomes. Taken overall, the results of the project will provide timely and relevant evidence to federal and provincial policy makers, as well as all Canadians, when Pharmacare reform is increasingly on the policy agenda.
The Next Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy
In photodynamic therapy (PDT), a nano particle (NP), is placed within the body and is illuminated with light from outside the body. Normally, the light that gets absorbed by the NP can produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them, like tumours. This type of light therapy can also be employed to release small drug molecules from the surface of the NP. PDT can be far less expensive than radiotherapy or surgical operation and post operative care. Furthermore, PDT recovery typically requires hours or days rather than weeks, and does not leave a toxic trail of reactive molecules throughout the body as is the case with chemotherapy. This is because the light is targeted at the precise location of the NPs. PDT therefore, is potentially a non-invasive procedure for treatment of diseases, growths and tumours. Additionally, NPs with multiphoton upconversion properties are useful for the diagnosis and treatment of cancer and hold great promise for biosensing and bioimaging. Dr. John-Christopher Boyer is involved in designing the next generation of multifunctional NPs capable of both imaging and selectively targeting cancer cells using photodynamic therapy based on molecular switches. The ultimate goal of his project is to develop nanoparticles with photon upconversion properties, and apply them in sensitive cancer detection. Consequently, a focus of his current research project is to evaluate the performance of the upconverting NPs when applied to sensitive detection and treatment of prostate cancer. Dr. Boyer’s research could significantly enhance Canada’s position in nanomedicine, and developments in this area may well revolutionise medical practice in cancer detection and treatment over the coming years.
Exposure assessment for women’s occupational exposure to carcinogens and other hazardous substances
Studies that have evaluated workplace exposure to hazardous chemicals and associated health outcomes have traditionally focused on men in male dominated jobs such as manufacturing and other heavy industries. Consequently, women weren’t generally included in the earlier studies and the industries in which they worked weren’t regarded as important. This, in turn, negatively affected women’s access to workers’ compensation compared with men, especially with respect to injuries, stress and lung diseases from asbestos. However, the research focus has recently shifted to include the changing role of women in the workplace and subsequent hazardous materials exposure that might adversely affect their health. The CAREX study, currently underway in Canada, is a national surveillance project aimed at estimating the number of Canadians exposed to environmental and workplace carcinogens. Cheryl Peter’s research will augment the CAREX project by looking at how these types of exposures differ between men and women. Her study identifies research gaps in women’s occupational health in general, and industries or jobs where women are more susceptible to exposures or adverse health outcomes specifically. The results of this study will help improve the health of female workers by identifying women at higher risk of exposure to hazardous chemicals, and may also help to prevent future health problems, including cancer. Further, Ms. Peter’s data will inform researchers with respect to improved research methods and recommendations on improvements for future studies, accounting for differences in exposures on the job between men and women.
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.
The influence of technology on pedestrian safety behaviour
The use of personal electronic devices, such as cell phones and Pods, in everyday situations is a growing safety concern, and there is a common belief that all personal electronic devices threaten pedestrian safety in the same way, that is via distraction. However, recent data indicate that cell phones and iPods influence pedestrian safety behaviours (e.g. looking both ways before crossing a street), in qualitatively different ways, and that cell phones and iPods have different effects on an individual’s behaviour in naturalistic contexts. Building on her earlier research in this area, Sophie Lanthier’s current project will test the hypothesis that cell phone and iPod users are affected differently by these devices: specifically, that cell phone users’ conversations absorb general-purpose attentional resources (i.e. they are distracted from their environment), which increases their likelihood of being in an accident, whereas iPod listeners are not distracted by their music, but rather the music limits auditory input from the environment, rendering them unable to hear unexpected events that could occur after they begin to cross the street. This inability to adapt to a potentially important change in the environment (i.e. a car that has just turned onto the street), could increase an iPod user’s likelihood of being in an accident. This study will help to identify what cues individuals rely on to monitor changes in their environment and how personal electronic devices influence one’s ability to use these cues. With this information firmly in hand, methods to reduce risk in pedestrian behaviours can be undertaken.
Molecular dissection of the Campylobacter jejuni regulatory system CprRS and its control of key aspects of pathogenesis and biofilm formation
Campylobacter jejuni is the leading cause of bacterial food poisoning in the developed world. Infection with C. jejuni typically presents as severe gastroenteritis, termed campylobacteriosis, and presents as intense, often bloody, diarrhea, vomiting, fever and stomach cramps. Prior infection correlates strongly with autoimmune disorders such as irritable bowel syndrome, reactive arthritis and alarmingly, Guillain-Barré syndrome. Furthermore, antibiotic resistance is skyrocketing in C. jejuni isolates, and an effective human vaccine is not presently available. Currently, very little is known about the virulence mechanisms of C. jejuni. Even less is understood about how this fastidious organism survives and thrives in hostile environments, including those associated with environmental transmission and in vivo stresses such as acid, bile and the immune system. In her research, Sarah Svensson is characterizing the CprRS (Campylobacter planktonic growth regulation) two-component regulatory system (TCRS). TCRS represents ideal targets for antibiotic treatment due to their omnipresence in bacteria (and not humans) and control of phenomena related to virulence. By determining 1) genes that comprise the CprRS regulon; 2) how information is relayed from the environment through CprRS and connected regulatory proteins to elicit the appropriate physiological response; and 3) how survival strategies such as biofilm formation are controlled by CprRS, will contribute to our understanding of what makes apparently fragile bacterial pathogens such as C. jejuni so prevalent. As a result, this work will also provide a framework for design of novel infection control antimicrobial treatment, and vaccine strategies for an underappreciated bacterial pathogen.