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.
Research Location: University of Victoria
Small molecules with affinity for S100A7, a tumorigenic protein in breast cancer
Biochemical events in humans are influenced and triggered by cell signalling pathways and their associated feedback loops. Changes and mutations to members of these signalling pathways can cause cancer to develop. Trouble can also occur when alternative pathways are triggered or when built-in negative feedback (“”shut off””), loops are not triggered. In the case of cancer, the observed uncontrolled cell growth results in tumours that can eventually metastasize and send diseased cells throughout the body resulting in an aggressive, invasive cancer. Before the aggressive stage of cancer is reached, the disease often goes through stages of progressively worsening cancers. In breast cancer, Ductal Carcinoma In Situ (DCIS), is one such stage prior to invasive disease. With DCIS, the cancer is contained to a duct and has not yet spread to other areas of the breast or body. Research at the BC Cancer Agency’s Deeley Research Centre has revealed two proteins, S100A7 and Jab1, involved in a pathway associated with the transition from DCIS to invasive breast cancer. There is compelling evidence to suggest that if the interaction between S100A7 and Jab1 were prevented or disrupted, the critical signalling pathways would not be triggered and the progress of invasive breast cancer would be stopped. Amanda Whiting is researching the effects of blocking the interactions between S100A7 and Jab1 by using small, drug-like molecules. In particular, Ms. Whiting’s research uses the molecule 2,6-ANS, as the basis for modifications to improve binding to S100A7 and decrease binding to other important body proteins. Her research will provide an expanded understanding of small molecule binding requirements and, in turn, allow for appropriate modifications to the compounds. Moreover, her work explores a potential new target for breast cancer therapy using small molecule inhibitors to disrupt a cancer-associated protein-protein interaction.
A structure-function analysis of the exo-beta-D-N-acetylglucosaminidase StrH, an important Streptococcus pneumoniae virulence factor.
Streptococcus pneumoniae is a common bacterium that can cause serious infections like acute respiratory disease (pneumonia), infections of the brain and central nervous system (meningitis), blood infections (septicaemia, sometimes leading to sepsis), and ear infections (otitis media). This organism is one of the leading causes of death from infectious disease across the globe. In addition to showing a lethal synergism with the influenza virus, many strains of S. pneumoniae are rapidly becoming resistant to antibiotics and some strains have even been dubbed “”superbugs. From the practical perspective of combating S. pneumonia, there is a clear need to better understand how it makes us sick. Numerous studies have revealed that the ability of this germ to cause disease strongly depends on it attacking the sugars present in its host’s tissues. Dr. Pluvinage’s work focuses on one protein that performs this type of function, a large enzyme called StrH, which is necessary for S. pneumoniae to infect its most commonly targeted human organs, the lungs and the ears. StrH is responsible for removing an abundant sugar (N-acetylglucosamine) from the surface of host cells and the protective sugar layers found in mucus. Though the activity of StrH is known, precisely how it performs its job is not. Consequently, Dr. Pluvinage is working to characterize the protein’s complex, three-dimensional structure in order to better understand the protein’s function. The results of this research will provide a foundation for generating new small molecular inhibitors that might allow for the effective treatment of infections caused by S. pneumoniae “superbugs”.
Examining the link between cognitive deficits in the elderly and suboptimal activity of the locus coeruleus-norepinephrine system
A working brain produces electrical activity that can be recorded at the scalp. An event-related potential (ERP) is a characteristic electrophysiological response to any specific category of stimulus or event. The P300 is an ERP associated with stimuli that must be attended. It has been suggested that the P300 may be a manifestation of functioning in the locus coeruleus – norepinephrine system (LC-NE system), a neuromodulatory system that is associated with arousal , vigilance and attention. A link has been suggested between cognitive deficits in the elderly and suboptimal activity in the LC-NE system. Christopher Warren is attempting to demonstrate the link between the P300 and the LC-NE system, and describe the related changes in the brain that occur with age. He is assessing the performance of elderly participants on a specific attentional task, while simultaneously recording the electrophysiological activity of their brain using electroencephalograph recording equipment. The data will be compared with a control group of younger participants. Chris is looking for specific, key differences in electrophysiological activity and behavioural performance between elderly participants and controls, which will support the link between the LC-NE system and the P300, and will allow inference as to how the LC-NE system is behaving in the elderly participants.. Chris’s results will describe, and possibly implicate suboptimal function of the LC-NE system in cognitive decline with age. This research has direct implications for understanding the cognitive decline associated with healthy aging, potentially describing the function and malfunction of the LC-NE system in aging populations. It could also generate a model that could be applied to understanding LC-NE function in people with attention deficit/hyperactivity disorder, dementia, schizophrenia, or traumatic brain injury. A comprehensive theory of the LC-NE system could inform the development of clinical strategies and tools to help elderly citizens effectively work around attention-related cognitive deficits that occur with age
Polysubstance use: psychosocial functions of combined use of alcohol and psychostimulants
Much of the research that informs current understandings of drug and alcohol use and addictive behaviour is based on studies that concentrate on a single substance type. This narrow focus is in distinct contrast to actual patterns of use and related harms: most Canadians with substance use problems use more than one substance (polysubstance use), often on the same occasion, and their behaviours and health outcomes may be strongly shaped by this combination. Health policies and programs are usually developed, implemented and evaluated one substance or behaviour at a time, without consideration of possible consequences for other substance use and addiction outcomes. In the current research literature there is a lack of information regarding polysubstance use. This includes when, in what order, and in what quantities people use substances, why they choose to use simultaneously, and the risk behaviours (e.g. sexual behaviour, spending behaviours) associated with simultaneous polysubstance use. Kristina Brache is exploring the patterns of use, the settings and the motivations associated with combined use of alcohol and psychostimulants (cocaine, amphetamines). She is conducting a series of in-depth interviews and self-administered surveys of 150-200 substance-using individuals in a treatment setting. Understanding the use of multiple substances can inform prevention and intervention strategies to reduce harm or risk to individuals using multiple substances. Ultimately, this research could improve health and health delivery systems by informing policy, programs and treatment about combined drug use in this population of interest.
Towards a better understanding of adolescent depression: the roles of relational victimization and emotional support
The onset of depression in many individuals can be traced back to adolescence. Up to one-third of 12- to 16-year-olds report “feeling depressed,” and clinical depression among adolescents is associated with numerous adverse consequences, including increased risk for recurrent depression, suicide, hospitalization and general maladjustment. Adolescent depression has been identified as a chronic, continuous disorder that is in need of increased research attention. The prevalence of depression increases dramatically as children transition into adolescence. This is also consistent with increases in relational aggression, such as gossiping, name calling, and social exclusion. Interestingly, striking gender differences in the rates of depression also emerge at this time: adolescent girls’ rates increase more rapidly than boys’ rates of depression, and depression remains more prevalent in women than men. Researchers have suggested that interpersonal orientation is one of the most consistent psychological differences between males and females, and that females may be more psychologically vulnerable to peer victimization because they view their strong emotional attachments with others as central to their self-concept. At the same time, however, aspects of interpersonal relationships may serve to protect girls’ emotional reactions to relational aggression. Tracy Desjardins is examining the effects of peer and parental emotional support on adolescents’ emotional reactions to peer victimization, investigating whether they may be contributors to gender differences in emotional maladjustment. Her primary goal is to help dismantle the precise mechanisms by which certain interpersonal risk factors interact to produce depression at differential rates in males and females. Desjardins’ findings will contribute to increased knowledge about the origins of adolescent depression. Ultimately, this work could lead to more targeted treatment interventions and prevention strategies that consider differential gender processes.
Predicting relations between child language brokering and psychological health within immigrant Chinese families
People of Chinese ancestry make up the largest visible minority group in Canada and they comprise a major percentage of new immigrants to the country. Adaptation to life in a new Western country for Chinese immigrants often comes with stress and hardship, including language barriers and school or employment adjustments. In addition, family members may adapt to the new culture at different rates, creating additional stress that may result in new areas of conflict within the family and increased risk for poorer psychological health. Often, children are relied upon to provide interpretation and translation for their non English-speaking parents. Current research is divided on whether this role harms or supports the psychological health of children — reports cite outcomes that range from psychological distress and depression to pride and increased confidence. Tapping into data gathered through a larger Intercultural Family Study at the University of Victoria, Josephine Hua is studying 180 immigrant Chinese families living in Victoria or Vancouver. She’s examining the psychological implications of language brokering for both children and parents. She hypothesizes that children’s psychological health relating to this role depends on the underlying conditions and relationships within the family. For example, a child who feels pride in fulfilling family obligations is more likely to benefit from this role. Identifying the determinants of psychological health related to language brokering for both children and parents within immigrant families will suggest strategies for promoting healthy integration into Canadian society. Ultimately, this could help alleviate the economic and psychological costs associated with maladjustment among new immigrant families.
Is there a “low-risk” drinking level for youth? Exploring the harms associated with adolescent drinking patterns
Substance use among youth continues to be a large public health concern, including alcohol consumption among underage youth. While much research has explored youth involvement in substance use and on the negative impacts of that use, there is a lack of consensus in the literature about how to approach the prevention and treatment of youth substance use. A focus on abstinence as the only acceptable outcome is a key controversy in prevention and treatment approaches. While Canada’s laws support abstinence as the desired stance for substance use, studies show that zero-tolerance approaches to drug and alcohol prevention are often ineffective. There is some evidence of the effectiveness of harm-reduction strategies, which focus on reducing youth’s levels of risk and experiences of harm from substance use. While there are low-risk drinking guidelines for adults in British Columbia, there are currently no accepted low-risk drinking guidelines for youth, nor a clear consensus on whether any alcohol consumption by youth below legal drinking age can be considered acceptable and low risk. Kara Murray is drawing on existing research literature and survey data to explore the issues of underage alcohol consumption and its health outcomes. She’s assessing the risk of harm at different levels of alcohol consumption, specifically at low frequency and low quantity of use as outlined in the Canadian low-risk drinking guidelines. She’s also identifying whether there are age or gender differences at different levels of alcohol consumption. Murray’s research will contribute to the advancement of knowledge by attempting to formulate a continuum of risk that identifies distinct levels of hazardous and non-hazardous alcohol use for youth. Ultimately, her work could inform changes to the current prevention and educational strategies that are used.
Analysis of a carbohydrate active pneumococcal virulence factor
While the bacterium Streptococcus pneumoniae is found in 10-40 per cent of healthy people with no ill effects, it is the cause of common diseases including pneunomia, meningitis, and ear infections. Unfortunately, more and more penicillin-resistant strains of S. pneumonia are becoming prevalent, and these strains are also developing resistance to other antibiotics. There are still a few antibiotics available to treat S. pneumoniae, but resistance to these drugs will also certainly emerge. New, more effective ways to treat bacterial infections are urgently required. Bacteria have adapted the ability to use different carbohydrates, or sugars, for a number of biological processes such as metabolism. S. pneumoniae has a number of protein enzymes devoted to carbohydrate metabolism, including a pathway dedicated to degrading (breaking down) the sugar fucose. Certain proteins in this pathway have been found to be important in some aspect of S. pneumoniae infection and disease. Melanie Higgins is focusing her research on a protein called GH98. GH98 is found on the outside of the bacteria and is thought to be the first step in this fucose degradation pathway. In order to better understand how this enzyme works, Higgins will first determine the three-dimensional structure of GH98. From these structures, she will develop synthetic inhibitor molecules that keep GH98 from functioning. Her work will answer whether S. pneumoniae can still infect host cells and spread disease in the absence of GH98. If these inhibitors are proven effective, they could become a novel treatment for S. pneumoniae infections, providing clinicians more options for treating a number of bacterial diseases.
Public Health Services Renewal in BC
Canada’s public health system faces serious systemic challenges for adequately meeting the health needs of the population. To help guide a plan for improvement and renewal of public health services in BC, the BC Ministry of Health has developed a Framework for Core Functions in Public Health. This framework defines the core activities of a comprehensive public health system, and serves as the roadmap by which the province is planning and investing in public health services. By studying the implementation and outcomes of the Core Functions Framework, this team will contribute new knowledge for BC and Canada regarding ways for public health system renewal to improve population health, reduce health inequities, and better integrate with health services. This team received an MSFHR Team Planning Award in 2006. MSFHR’s Team Start Up grant will now support the team — which comprises academic researchers and key decision-makers at the provincial, regional, and national levels — to further develop its productivity and competitiveness.