Each year in Canada about 100,000 people develop sepsis—a severe illness caused by the presence of bacteria in the bloodstream. The condition causes blood pressure to drop, resulting in shock and may lead to multiple organ dysfunction and eventually death. With a mortality rate of 30 and 65 per cent respectively, sepsis and septic shock cause more deaths annually than heart attacks. Inflammation and immune response to infection varies greatly between patients. Some inflammation is a normal defense against infection. However, if inflammation is excessive, white blood cells and other cells can spill into the circulatory system and damage healthy organs. Continuing her previous MSFHR-funded research, Ainsley Sutherland is studying whether the genes that recognize bacteria and viruses play a role in determining which patients will develop the excessive inflammation that can lead to sepsis. This understanding could lead to the development of drug therapies for patients at higher risk of sepsis, and the avoidance of unnecessary drug side effects in patients who are not at risk.
Research Pillar: Clinical
Biophysical Investigation of Mutations In The P/Q Type Calcium Channel Associated With Familial Hemiplegic Migraine
Migraines affect about 15 per cent of the population, with the incidence being two times greater in women than in men. Symptoms of common migraines include pain, nausea, vomiting, sensitivity to light, sound, and smells, sleep disruption, and depression. Progress in developing new treatments has been slow due to a lack in understanding regarding the complex genetic roots of the disorder. Familial Hemiplegic Migraine (FHM) is a sub-type of common migraines with similar symptoms, but with simple genetic roots, making FHM a good model for study purposes. Most patients with FHM experience a visual aura – such as shimmering lights, wavy images or temporary vision loss – before the headache starts and varying degrees of paralysis in one side of the body (called hemiparesis). The symptoms can last from a few minutes to several days, in some cases outlasting the headache. About 50 per cent of patients with FHM have mutations in the CACNA1A gene. Paul Adams is investigating these mutations to better understand the molecular mechanisms that underlie migraines – an important step towards developing effective new treatments to alleviate all migraines.
Characterization of SNARE complex proteins in severe mental illness
Schizophrenia is a severe psychiatric illness affecting one percent of the general population. It typically begins in early adulthood and often has a devastating effect on an individual’s quality of life and functioning in society. The diverse and debilitating symptoms associated with schizophrenia include hallucinations, delusions, dampened emotion and poverty of speech. It has been hypothesized that faulty neuronal function may contribute to these symptoms. Communication between neurons is achieved by neurotransmission at synapses. Because soluble NSF-attachment receptor proteins (SNAREs) mediate this process, they are important in neuronal communication and normal brain function. Altered levels of SNAREs have been found in patients with schizophrenia, which may mean that abnormal levels of SNARE proteins disrupt normal transmission of synapses, contributing to the disorder. Vilte Barakauskas will compare SNARE protein levels from control subjects and from people with schizophrenia to identify differences in the brain. She will also attempt to identify the significance of SNARE properties in their role in neurotransmission. This information will increase our understanding of why brain function may be altered in people with schizophrenia. By comparing protein properties between control subjects and those with schizophrenia, Vilte is looking for molecular mechanisms that may contribute to altered neurotransmission. This may ultimately lead to new treatments for, and a better understanding of, this psychiatric disorder.
The Role of Dopamine in Depression
Parkinson’s disease (PD) is a progressive neurological disorder that typically begins with minor motor impairments and eventually progresses to severe immobility, as well as mood and cognitive dysfunction. About 40 per cent of patients experience major depression, marked by hopelessness, inability to experience pleasure, suicidal thoughts and delusions/hallucinations. While depression is an understandable reaction to living with a chronic and potentially debilitating illness, the rate of depression in PD patients is nearly double the rate of depression seen in comparably disabled patients with other chronic illnesses, indicating the likelihood of a neurochemical element. Common to this motor disorder and mood disorder is the neurochemical dopamine, a neurotransmitter that is involved in many brain activities, including movement and emotion. Elliott Bogusz is investigating the role of dopamine as it relates to depression in Parkinson’s disease patients. He is identifying differences between depressed and non-depressed PD patients using Positron Emission Tomography (PET), a neuroimaging technology, to visualize dopamine activity in the brain. This research could provide insight into the development of Parkinson’s disease and the neurochemical activity associated with depression. It also may contribute to the development of dopamine-related therapy in the treatment of depression and to screening depressed patients for Parkinsons.
Seniors at high risk of falls: Clinical and economic studies
Falls among older people are a major health problem. In Canada, hospital emergency departments report that 86 per cent of seniors’ injury-related admissions are due to falls, and individuals who present to an emergency department after one fall are at particularly high risk of falling again and incurring significant injuries. Current practice guidelines encourage a sophisticated and costly program to prevent subsequent (secondary) falls, including referrals to physiotherapy, ophthalmology, family practice and occupational therapy. However, despite the proven effectiveness of this approach, current “real life” practices throughout BC do not generally follow these guidelines, and the outcomes – both physical and economic – have not been studied in a Canadian context. Working within VGH’s Falls Prevention Clinic, Jennifer Davis is conducting the first Canadian randomized controlled trial to compare secondary falls and fall rate between seniors receiving “gold standard” care at the Clinic versus those receiving the standard of care with their GP. She will also detail health resource utilization for all study participants in order to analyze the cost-effectiveness of the Clinic intervention versus the standard of care.
The relationship between emotion processes and health in children at-risk for the development of anxiety disorders
While feeling shy, uncertain, or apprehensive with strangers or in new situations is common in young children, an excessive display of these behaviours can negatively affect day-to-day functioning. Disruptions in friendships and social activities, decreased school attendance and performance, and increased family conflict are all common consequences of extreme shyness. Research shows that children who consistently respond in these ways are more likely to develop anxiety disorders later in childhood and adolescence. Furthermore, older children and adults who display this pattern of behaviour have more general health complaints and problems. Sherri Frohlick is conducting a study aimed at understanding the development of these general health complaints by examining the ability of preschool-aged shy children to understand and express different emotions, and determining the effect of this on their health status. Just as being able to identify and communicate different emotions is an important part of healthy psychological growth, not having these skills is linked to emotional and behavioral problems such as depression, anxiety, aggression or other serious forms of psychological dysfunction. By examining emotion identification and communication as processes underlying health complaints and problems in young children, Sherri is working to develop prevention and intervention programs that identify their needs more directly and lessen health concerns. A reduction in health complaints would lessen the burden on a health care system faced with the challenge of diagnosing and treating these problems.
Respiratory system limitations during exercise in women undergoing healthy aging
There is evidence to suggest that healthy men and women experience respiratory system limitations during exercise, such as respiratory muscle fatigue, a limited ability to exhale, and an abnormal exchange of oxygen and carbon dioxide in the lungs. Young active women may be particularly susceptible to these limitations due to their inherently smaller lungs and airways compared to men of equal stature. Unfortunately, there have been few studies aimed at understanding how the female respiratory system responds during exercise. Since healthy young women are predisposed to these limitations during exercise, then healthy elderly women may be particularly vulnerable due to the decline in lung function that occurs as a result of the normal aging process. This decline occurs because of a reduction in “elastic recoil,” which is the ability of the lungs to stretch and inflate. Jordan Guenette is studying the relationships between the respiratory system, exercise, gender, and healthy aging. His goal is to identify the respiratory limitations women face as they age. This information could be used to design exercise rehabilitation programs tailored to meet the needs of different patient populations.
Cognitive Bias in Subsymptomal Seasonal Affective Disorder
Canadians, like other people living at higher latitudes, often experience seasonal changes in sleeping patterns, appetite, mood, and energy levels between the winter and summer seasons, but there has been little research to explain why. Fern Jaspers-Fayer is studying the impact of season on thoughts, moods and behaviour. These changes occur along a continuum from normal to abnormal, with severe winter depression, or Seasonal Affective Disorder (SAD), at one extreme. Fern is identifying the changes in electrical brain activity associated with SAD, and will determine whether these changes disappear in the summer. The results should help explain the brain mechanisms involved in SAD, leading to better therapies for the condition and better ways for everyone to chase away the winter blues.
Femoroacetabular impingement as a predictor for Osteoarthritis of the hip
Osteoarthritis (OA) is a debilitating disease characterized by the degeneration of cartilage. OA is a common disease among the elderly, affecting more than three-quarters of people over the age of 75. Research has suggested a link between the development of OA and femoracetabular impingement syndrome (FIS), a disease of the hip. In FIS, the femur makes contact with the acetabulum (the cup-like recess in the pelvis that acts as the socket in the joint), causing pain. This is most evident during periods of extreme range of motion and often occurs due a structural abnormality of either the femoral head or the acetabulum. Early detection of FIS has the potential to allow doctors to alleviate or arrest the onset of osteoarthritis. However, radiographs, which are the current standard of diagnosis, have limitations. Joshua Levitz’s research seeks to develop a better way to diagnose FIS. His study involves creating computerized, 3-D bony models of hips from MR images, to study hip alignment in both subjects diagnosed with FIS and healthy control subjects, and determine the significant factors characterizing FIS. By developing a more sensitive gold standard for diagnosing FIS, this research may provide a method for early prediction of OA.
Prefrontal-cortico-amygdalar circuitries underlying cue-induced reinstatement and the effects of amphetamine sensitization on responding for food reinforcement
With drug addiction, people typically resume seeking drugs if exposed to cues associated with the drug. This phenomenon, called cue-induced reinstatement, is frequently studied, but a number of neurological issues have yet to be addressed. Two parts of the brain may be a common link in the neural circuitry underlying these cue-induced responses. These are the amygdala, the portion of the brain that regulates emotions, and the prefrontal cortex, a part of the frontal lobe involved in executive functioning. The two areas respond differently to cues for food rewards than to drug cues. Ryan McLaughlin is investigating the similarities and differences in how these areas of the brain regulate food and drug rewards to determine if the difference results from long-term alterations in brain function, brought about by repeated drug use. If so, this research will confirm that chronic drug abuse can radically alter how the brain processes information and could eventually lead to new treatments for people trying to recover from drug addiction.