During my psychiatry residency at McMaster University, I became interested in understanding why I was seeing so many patients on the inpatient unit with diabetes, cardiovascular disease and other illnesses that really affected their psychiatric care. Dr. Arya Sharma had just been recruited to be Canada’s first obesity research chair, and I asked if he would help me create a research program on the relationship between mental health and metabolic-related diseases. It ended up being the first multidisciplinary metabolic clinic in Canada.

I was particularly interested in understanding individual vulnerabilities to co-occurring psychiatric and medical problems; for example, which issue comes first, the weight or the depression? Trying to answer that question meant going back in time—all the way to pregnancy, hence my interest in women’s health. Ultimately, mental health is married to physical health, and both should be studied and treated concurrently.

I’m very interested in health systems and how people move through the system, especially with respect to medical psychiatry. Understanding the different pieces—hospital networks, family practice, community care, other partners— and how they work together is a huge focus, because streamlining care is very important. For me, another key aspect of this role is mentorship. I’d like to ensure support for researchers, and all staff, at CAMH and at WHC.

We're working on an entirely new area of study, which is whether or not psychiatric illnesses such as major depressive disorder (MDD) are associated with certain bacteria in the gut. We’re examining changes in these bacteria before and after treatment with antidepressants, and exploring whether there are differences in gut bacteria between people with and without depression.

Gut bacteria is affected by nutrition and appetite, so we’re asking our study participants to track their diets in detail. How diet affects health and disease is substantially under-researched. The aim is to answer key questions regarding microbial factors that contribute to mental illness. Understanding these links could be extremely beneficial for both prevention and treatment.

WCH and CAMH have some complementary programs and a shared expertise. It’s a perfect combination, particularly when dealing with mental illnesses that by nature involve myriad factors and comorbidities.

So far, as a partnership, CAMH and WCH have developed a transitional program between inpatient and outpatient care called P-STEP (Psychiatric Structured Treatment and Evaluation Program) to ensure that when people leave hospital care, all the medical pieces that sometimes get missed are taken care of; for example, managing medications or organizing home care. We’re also piloting an evaluation scale to see if we can predict higher rates of hospital readmission among inpatients. If the scale can be validated, it will be a huge asset that we can export to the community. These projects really marry the competencies of both organizations.

We have a study on reducing stigma among health professionals in seven community health centres (CHCs) in Toronto that serve diverse and marginalized populations. It’s a multi-faceted intervention, including training, leadership development, public education, a recovery-based arts component, and policy and procedure analysis. First we ran a three-year pilot project to develop this intervention, and preliminary results were positive. Earlier this year, we received a grant from the Canadian Institutes of Health Research to run a full trial of the intervention. It’s a cluster randomized controlled trial (RCT), meaning some centres will get the anti-stigma intervention and others won’t, so we can look at its impact.

We’ll be studying this same anti-stigma intervention in Peru, with a Grand Challenges grant. But our research in this area began in 2006, after an external review of our work in South America showed that one of our most significant outcomes was a reduction in stigma. Health professionals who were previously hesitant or unwilling to treat clients with substance use or mental health problems reported a change in attitude and practice. CAMH’s interprofessional and biopsychosocial approach to treatment provided an impetus, and enhanced our international learners’ motivation to approach these clients in a different way. We realized that we could make both a global and a local impact in reducing stigma. This realization led us to redouble our efforts in this area.

I’d say that it’s essential to have strong project teams, take time to build solid relationships, be opportunistic about funding opportunities, and be persistent. We’ve had many rejections and kept on applying. During the interim, we conducted many low-cost academic exchanges to maintain international relationships and to keep commitments strong. Our ability to have a global reach is only possible because all work is done through interdisciplinary teams, which is crucial for our partners because of resource limitations in low-income countries. Having flexibility allowed us to adapt to a steady stream of changes among the donor community.

We approach all our work as respectful learners, expecting that some technologies will be culturally and socio-economically relevant while some will not. We plan a process of cultural screening as a first step in our collaborations. CAMH also has an incredible array of multicultural expertise and talent that allows us to work well within many different cultural settings. For instance, we’ve developed culturally adapted cognitive-behavioural therapy (CBT) resources in French, Spanish and English, which are being used in related efforts abroad. We’re planning a pilot study in Haiti, where spiritual leaders will be taught this culturally-adapted CBT. Our co-investigators are the heads of Haiti’s main spiritual traditions and religions—voodoo, Catholic and Protestant. The nature of the work and teams give our collaborations a lot of credibility on the ground.

We also need to contribute as much as we can to alleviate the tremendous inequities in mental health care, which are an affront to human dignity. I’ve seen much unnecessary human suffering. This realization keeps me going when the going gets tough.

Depression has a negative effect on brain functioning. And the risk of depression and other brain-related illnesses such as Alzheimer’s disease increase as we age. Indeed, it’s been proposed that depression is an illness of accelerated aging.

At the biological level, we’ve found a striking overlap between the molecular pathways associated with age-related changes over a lifetime, and depression and other psychiatric and neurodegenerative illnesses.

So I realized that studying the normal aging of the brain could help us understand the cellular and molecular mechanisms underlying changes in depression. My focus is to use this approach to identify new targets for treatment or prevention of depression.

My lab has shown that aging has a large yet specific effect on multiple genes, influencing how these genes function and produce proteins. We’ve shown that many of these age-related changes are strikingly similar to those we see in brain-related illnesses, including depression.

One example is a protein called brain-derived neurotrophic factor (BDNF). BDNF is important for brain development and healthy functioning of neurons. We know that BDNF levels are lower in people with mood-related disorders, and in healthy older adults. We’ve now showed that BDNF levels decline over time in both cases, although it happens earlier in depression.

Another of many examples is with the genes coding for a type of chemical called an inhibitory neurotransmitter, which helps maintain chemical balance in the brain.

It’s true that biological changes alone do not necessarily lead to symptoms of depression among older adults.

To understand why, I have proposed a model of age-by-disease interaction. Aging is a continuous lifelong process, in which our bodies constantly adapt to counter biological changes related to aging, and to maintain a biological balance. Many of these changes are essential responses to the environment.

We believe that problems emerge when the timing of these changes is off. At a younger age, for example, lower BDNF levels might disrupt key neural networks and lead to problems with mood regulation. Most older adults would have adapted to the decline in BDNF levels over time, and don’t show symptoms.

Yes. First, we need to understand which biological and cellular processes in the brain are engaged during aging. Second, we look for changes in the same processes in depression. The key is then to identify which other factors—or moderators—affect the trajectory of those changes.

Moderating factors, which may be environmental or genetic variations, may accelerate or slow down changes in BDNF or chemical inhibition, especially in a middle-aged person. If we can identify the overlap between age, brain illnesses and moderating factors, it might provide a target for intervention.

We are also looking at targets that delay age-related changes, which could protect some people from developing depression.

One project involves identifying genes related to chemical inhibition in depression. We are broadly looking at biological changes related to inhibition that involve GABA, which is the major inhibitory neurotransmitter.

We are also using genetic variations as a way to translate our basic science findings of the human brain to population studies. I’ve begun working with data from two large studies that track people as they age—the Health ABC and the Cardiovascular Health Studies. We are studying physical and mental changes related to genetic variations, among the genes identified in our studies of aging and depression.

My background is in molecular biology, working with animal models. Because of the limitations of these models, I thought it was important to study actual occurrences of depression from the genes and brain tissues of people affected by this illness. Using Columbia University's and then the University of Pittsburgh’s post-mortem brain banks, I was able to identify a new cellular target related to GABA, the major inhibitory chemical, and somatostatin, a cellular marker of specific GABA neurons. Based on these findings, I was then able to develop more informed animal models. I continue to use both post-mortem tissue and animal models in my work, combined with molecular and bioinformatics approaches.