Walking away from depression: Leveraging physical activity to treat symptoms and improve well-being in individuals with major depressive disorder

Major depressive disorder (“MDD”) is a chronic condition characterized by sadness and loss of pleasure. MDD is a leading cause of disability (WHO, 2020), and costs the Canadian economy billions each year (CAMH, 2021; CASHC, 2016). In 2016, the Canadian Network for Mood and Anxiety Treatment recognized exercise as a first-line treatment for MDD. This statement should have revolutionized care: not only does exercise reduce symptoms, but it also improves health and quality of life. However, the past five years have seen little progress in “mainstreaming” exercise as a treatment option. This means patients are being denied access to a safe and effective treatment.

We are left with a question: How can we get more people with MDD more active more often?

The purpose of my postdoctoral fellowship is to answer this question. I will oversee a program of research that examines how British Columbia’s public health system can provide exercise as a treatment for MDD. I will investigate barriers to uptake; strategies to overcome barriers; and engage in program development and evaluation. This research will be conducted in collaboration with patients, healthcare providers, and communities to ensure it is feasible, relevant, and sustainable.

Psychiatric morbidity in multiple sclerosis during the prodromal period (Psych-MS)

Multiple sclerosis (MS) likely begins years before the first neurological symptom by a set of not-clearly defined, subtle symptoms, leading patients to increasingly seek medical attention years before diagnosis. Some may even require psychiatric care during this period. This phase of the disease is known as the MS prodrome. Our plan is to better characterize psychiatric healthcare encounters during this phase of the disease by analyzing anonymized and linked administrative health data that is generated whenever an individual visits a doctor, is admitted to a hospital, or fills a prescription at a pharmacy. We aim to specifically look at any visits resulting in a diagnosis of depression, anxiety, or bipolar disorder by a physician, any visits to psychiatrists, and also look at prescriptions filled for medications, such as antidepressants. These ‘psychiatric data’ generated during the five years before patients’ first MS symptom will be explored and compared to that of individuals from the general population. We believe that advancing our understanding of the MS prodrome may help us identify patients sooner in their disease course, allowing for earlier treatment, and eventually prevent disease progression.

Using a mobile health aerobic exercise program to improve psychological distress in healthcare professionals: A randomised controlled trial

Healthcare professionals account for the largest sector of government employees in Canada and report more than twice as much high work stress and greater depression than the average employed Canadian. Due to the current pandemic, healthcare professionals are now reporting an increase in their depression, anxiety, and distress linked to their risk of becoming infected with COVID-19, quarantine and isolation, and being separated from their families. The stress faced by healthcare professionals should be cause for concern among our public health organizations, as stress has serious health consequences for healthcare workers, including medical errors, depression, burnout, absenteeism, and premature mortality. I am proposing to conduct a randomised trial of an aerobic exercise mobile app intervention (yoga and whole body weight-based training) that requires little physical space or equipment and is easily completed at home or in a small office, to improve healthcare professionals’ psychological distress and wellbeing. This work is expected to provide a feasible, engaging, and accessible solution to implement in every medical setting that will improve work stress, health, and quality of life among Canadian healthcare professionals.

T-cell repertoire analysis for immune monitoring in renal transplantation

Kidney disease affects 1 in 10 Canadians with an estimated cost of over $2 billion per year. Transplantation is the treatment of choice for kidney failure, but unfortunately approximately 30% of kidney transplants are lost to severe immune rejection. This leads to approximately 500 Canadians losing their transplant every year and returning to dialysis. These patients have a four-fold increased risk of death, decreased quality-of-life, and a cost of up to $1 million each to the healthcare system over their remaining life. Despite improvements in transplant care, there are still no proven methods to detect early immune rejection. Our goal is to develop a new minimally invasive blood-based test to monitor the immune system of transplant patients to detect immune rejection before kidney damage happens. This would allow transplant doctors to intervene early with powerful immune regulating medications and prevent irreversible damage to the transplant kidney. Our approach would not only benefit patients and their families with improvement in survival, quality of life, caregiver burden, and personal health expenses, but also the healthcare system, with reduced costs related to dialysis, re-transplantation, and improved organ availability.

A randomized controlled trial of a cognitive control intervention for major depressive disorder

Major Depressive Disorder is common and debilitating. Individuals with depression show biases toward negative, and away from positive, information– referred to as cognitive control biases. These lead to difficulty regulating emotions, unhealthy biological responses to stress, and ultimately, greater depression. Cognitive control biases are not adequately treated by current therapies. The objective of this clinical trial is (1) to test the effectiveness of a new cognitive control intervention (CCI) for depression and (2) to understand how it works. Participants will be assigned to a 4-week CCI group or a control group. Cognitive control biases, emotion regulation, and depression will be measured before and after CCI and 6 months later, and biomarkers of stress will be collected post-CCI. I predict that the CCI group will show improved cognitive control biases and emotion regulation, healthier biomarkers of stress, greater decreases in depression, and higher remission rates after CCI. Changes in cognitive control biases, emotion regulation, and biomarkers are expected to account for outcomes. CCI has the potential to be an accessible, virtual alternative to current therapies, and findings will inform our understanding of depression.

Advancing health equity in the cancer care sector: Identifying organizational and contextual factors impacting the integration of equity-oriented healthcare for marginalized populations

Alarming differences exist in cancer outcomes for people who are marginalized. Due to racism, discrimination and stigma, these groups experience extreme difficulties accessing cancer care and are diagnosed with cancers so late they have higher rates of preventable death than other groups. Some of these differences can be addressed using equity-oriented healthcare (EOHC), which directs resources to those with the most need, and reduces mismatches between health services and the actual needs of marginalized people. However, EOHC has not been studied within the context of cancer care. This study is about understanding the organizational contexts and conditions needed to build capacity for EOHC within cancer care in BC. We will: 1) conduct an environmental scan to identify strategies used elsewhere (Canada, internationally) to deliver EOHC in cancer care; 2) observe and interview key informants and healthcare providers who are trying to use EOHC in delivering cancer care, and marginalized patients who are trying to access cancer services, to better understand factors that support the provision of EOHC in cancer care. Results will be used to develop recommendations and action strategies to support cancer organizations to deliver EOHC.

The role of mechanics in EMT and cancer metastasis

The World Health Organization reports that cancer is the second leading cause of death globally, responsible for 1 in every 6 deaths. This ratio doubles in Canada, with the Canadian Cancer Society estimating that nearly 1 in 2 Canadians will develop cancer, and about 1 out of 4 will die from it.

Recent anticancer therapies target the epithelial-to-mesenchymal transition (EMT), a process that converts tightly bound cells into loosely associated motile cells. In cancers, this results in progression with metastasis and improved resistance to treatments.

Evidence shows the role of mechanics in driving EMT but how the biochemistry and the mechanics coregulate this process remains largely unknown.

We propose to investigate this question in the case study of stem cell cultures, which undergo EMT in a controlled environment. We will develop a mathematical model to link mechanical stresses and cytoskeletal energetics, and we will validate it experimentally in collaboration with the Zandstra Lab.

This proposal will enhance BC’s and Canada’s leadership in healthcare-oriented research, as understanding EMT is essential not only for cancer but also for many other biological processes, such as organogenesis and tissue regeneration.

Synthetic feedback control of TCR signaling to guide T cell development in vitro

T cells are an important component of our body’s adaptive immune system, helping to identify and overcome diverse diseases. An emerging treatment for cancer, viral infections, and other diseases is to engineer patient’s T cells to recognize and respond to diseased cells. However, because of the reliance on patient-derived T cells, such treatments are highly expensive. To lower costs and increase accessibility to T cell therapies, our laboratory is developing methods to generate T cells from an unlimited and readily-available source: human pluripotent stem cells. Pluripotent stem cells give rise to every cell in our bodies, including T cells, and can be grown indefinitely in laboratory settings. Our current process for producing T cells from stem cells has made great progress, but lacks control over key parameters such as whether the T cells will become “helper” cells that stimulate the immune system or “cytotoxic” cells that directly kill diseased cells, and if they will provide long-term memory or have strong, short-term effects. In this project, I will genetically engineer stem cells such that we can produce T cells with these diverse properties on-demand, thereby enabling the next generation of off-the-shelf T cell therapies.

Mapping chronic social isolation-induced brain activation in mice with machine learning-based phenotyping of behavioral deficits to pilot translational assessment of psychomotor disturbance

Loneliness is becoming increasingly recognized as a serious threat to mental health. Social isolation is detrimental to adult brain function and behavior across mammalian species. Chronic social isolation in rodents has been found to lead to depression-, anxiety-, and psychosis-like behaviors as well as signs of abnormal locomotor habituation, fear responses and aggression. However, our understanding of how and why social isolation is risky for health — or conversely — how and why social ties and relationships are protective of health, remains quite limited. Our lab makes use of advanced brain imaging and recording techniques to map connections between brain areas. We plan to use these techniques to help us to first understand the neuropsychiatric basis of chronic social isolation in animal models. A machine learning algorithm will be used to classify large behavior datasets automatically and objectively, and potentially uncover new pathological behavioral patterns that have been overlooked by human observers. Mapping large-scale brain functional connectivity associated with social isolation–induced behavioral deficits may shed light on the etiopathogenesis of mental disorders and lead to the identification of therapeutic targets.

Movement and young minds: Co-designing and integrating physical activity programming into health services for young people experiencing mental health and substance use challenges

In Canada, mental health and substance use (MHSU) disorders affect 25 percent of young people aged 12 to 24 years. Foundry is an organization in British Columbia (BC) made up of a number of centres across the province that offer a variety of services to young people with MHSU disorders. A service not yet offered is physical activity, which can be used to manage mental and physical health. An ideal time to help people develop healthy habits, including being physically active, is while they are still teenagers or young adults.

This study will explore how physical activity programming can be included as a service offered through Foundry centres. This will be done by using photographs to understand youth needs; development of a working group to consider how to add a service; and, co-creation of a physical activity program. This work will be done collaboratively with diverse youth, service providers, and researchers. The long-term goal is to improve the quality of care, and the health of young people with MHSU disorders living in BC, Canada and across the world.