June 2023

This month's brainbuzz™ features CAMH research demonstrating a link between brain inflammation and long COVID; the importance of studying maternal health; the creation of CARIBOU as an evidence-based integrated care pathway for adolescents with depression; and an evaluation of alcohol control policies nationwide. 

On behalf of the CAMH research institute, I wish everyone a safe and restful summer until our next newsletter in September. Please reach out at any time if you have any questions or feedback.

Aristotle Voineskos
VP Research, CAMH
 

CAMH study confirms ongoing brain inflammation associated with long COVID

Researchers using advanced brain imaging are first to find increase in protein marker of inflammation in illness affecting 200 million globally.

A new CAMH study published in the journal JAMA Psychiatry found elevated levels of inflammation in the brain of patients who report persistent symptoms of long COVID.

Using advanced brain scanning with positron emission tomography (PET) imaging agents developed exclusively by the CAMH Brain Health Imaging Centre, study senior author Dr. Jeffrey Meyer and his study team found elevated levels of the protein TSPO, a brain marker of inflammation, in patients with onset of depression within several months after a COVID-19 infection.

“We already knew that there is brain inflammation in people who died in the midst of a severe, active COVID-19 infection. What’s new about this study is that it shows that inflammation is hanging around for a long time in the brains of people with long COVID even after only mild to moderate symptoms of active COVID-19,” said Dr. Meyer, Head of the Neuroimaging Program in Mood & Anxiety at the Campbell Family Mental Health Research Institute at CAMH. “Inflammation in the brain was suspected of being the critical step in causing neurological and psychiatric symptoms of long COVID so confirming this is vital to develop treatments for people experiencing symptoms.” 

It is generally believed that the majority of the world’s population has experienced at least one acute episode of COVID-19, and that at least 5 per cent of those people—more than 200 million globally—may experience lingering neurological symptoms, including depression, loss of enjoyment, memory impairment, slower motor control, low motivation and energy, for months to even years due to brain inflammation from long COVID. 

As part of this study, 20 participants underwent brain scanning with specialized PET imaging designed to detect the presence of elevated levels of the TSPO protein. All had at least one documented acute episode of COVID-19 after which they reported symptoms of depression that continued for months. Most participants also experienced a variety of other lingering symptoms associated with long COVID, including extreme fatigue and problems with concentration and memory often referred to as ‘brain fog’.

“What’s also noteworthy is that the regions of the brain that had the most inflammation are the ones involved in the capacity to enjoy things, motivational energy and the ability to think and move quickly. These were often the symptoms of greatest concern among the people with long COVID who took part in the study,” added Dr. Meyer. 

In a pioneering 2015 study published in JAMA Psychiatry, Dr. Meyer found that the brains of people with depression had more inflammation—30 per cent more on average—than the brains of people who were not depressed. The greater the inflammation, the more severe the depression. It was the first time an association between depression and brain inflammation had been found. This research was so ground-breaking that it became one of the most highly cited international research studies ever produced to date by CAMH.

Dr. Meyer and his team believe that further study of the association between brain inflammation and depression, as well as further study on the short and long-term impacts of COVID-19 on the brain, could lead to new treatments for long COVID that would also be purposed for depression and other illnesses. “For people who have been suffering from long COVID with lingering symptoms of depression, the hope is that we can use anti-inflammatory medications to see if we can get a reduction in symptoms,” said study first author Dr. Joeffre Braga. “Since inflammation can be in response to injury, it might also give us insight into mechanisms of brain injury in neurodegenerative diseases like Parkinson’s and prompt therapeutic development.” 

This study was funded by the Canadian Institutes of Health Research (CIHR).

Read more about this research: https://www.camh.ca/en/camh-news-and-stories/potential-link-between-covid-19-and-brain-inflammation
 

Why studying maternal health matters

On World Maternal Health Day, a new CAMH-led study raises important questions.

Did you know that a pregnant person’s immune system responds differently depending on whether the fetus is a boy or a girl? Did you know that multiple sclerosis can go into remission during pregnancy? Did you know that some fetal cells migrate to the brain of a pregnant person and stay there for the rest of the person’s life with potential implications for long-term brain health?

A review of scientific literature on maternal health, “Beyond Sex Differences: Short- and Long-Term Effects of Pregnancy on the Brain” recently published in the journal Trends in Neurosciences, explores this chronically understudied area of research and finds evidence of major changes in short- and long-term neuroplasticity in the brain, inflammatory signaling and cognition.  It also finds many intriguing associations with as yet unknown significance that could have far-ranging implications for future treatment and research, all of which speak to the need for further research into sex differences in mental health.

Why do the tiny hairs in each human cell become shorter depending on how many children a person has had? Could that have implications for the aging process? Is there an association between how many children a person has and the risk for Alzheimer’s disease later in life? Why do people who have complications during pregnancy have greater risk for cardiovascular disease, stroke, and Type 2 diabetes later in life and what can be done to reduce those risks? 

“Historically in terms of medical research the view has been that females are just males with ovaries,” says lead author CAMH Senior Scientist and Treliving Family Chair in Women’s Mental Health Dr. Liisa Galea. “That is a simplistic view and one of the reasons why it has been so undervalued and understudied.”

On this World Maternal Health Day, Dr. Galea explains why studying maternal health is so important:

What was the purpose of this review? What were you hoping to find?
We wanted to draw attention to the fact that pregnancy itself changes the brain both short term and long term and look at how that may influence health. Women’s health in general is understudied, and one such area is how pregnancy affects the brain after the birth of the baby. Our lack of attention to women’s health costs lives and costs society. Science needs to prioritize the inclusion of female health variables such as pregnancy history to have a complete understanding of what drives risk and resilience for health and disease.

Do you believe this is based on a false premise that gender distinctions in neuroscience are trivial and not worth studying?
The short answer is ’yes’. It turns out that sex and gender matter for all health.  There are differences between sexes in cancer outcomes, bone fractures, lung disease and cardiovascular disease, as well as brain diseases. What can we learn from studying female-specific experiences like pregnancy?  Multiple sclerosis (MS) often undergoes remission during pregnancy.  What is it about pregnancy that may be causing that? Could that lead to new therapeutics for MS for men, women and gender-diverse individuals? There are clinical trials going on right now. The other way to think about it is that by ignoring the influence of female-specific experiences or sex and gender we are missing this richness of information that can inform our knowledge of new treatments.  Maybe part of why we don’t have solutions to illnesses we have been studying for years is based on this one-size-fits-all approach. 

Talk about what is sometimes called “baby brain” and the evidence that grey matter does shrink during pregnancy.
Total brain volume does decrease during pregnancy up until childbirth.  But it does bounce back within six months.  It turns out while total brain size doesn’t change after pregnancy, different areas in the brain do change quite a bit, as some are reduced but others are increased.  In fact, those reductions in grey matter are related to better communication between different cell pathways and greater maternal attachment.  You can think about the reduction in gray matter as perhaps noise reduction – more is not always better!

Are there implications for more specific women’s health issues like postpartum depression or psychosis?
What’s fascinating to me is that a lot of the biomarkers for depression are mimicked in the postpartum period. Maybe it’s not so surprising that we see the greatest risk to develop depression during the postpartum period because it’s like a perfect storm. If you are already more susceptible to depression, the biological outcomes after pregnancy may tip the balance. A number of countries have strategies to deal with the postpartum period to improve the lives of the birthing parent and the family.  Unfortunately, Canada is not one of them and we really have to step up.

How does the sex of the fetus impact the health of the mother?
One factor is that if you are pregnant with a boy, he’s an XY (chromosomes) and you’re an XX, so it can impose a greater inflammatory challenge. It might have different pregnancy repercussions than if you are pregnant with a girl. It’s astounding to me that the few researchers who study maternal health do not consider fetal sex as an important factor.

Does this study go to the heart of the womenmind™mandate?
Yes,womenmind™is a community of philanthropists who really want to raise awareness about the gender gap in science, advance research on the mental health of women and girls, and to advance women in science. This area of science is very understudied. We have to ask ourselves, ‘What else are we missing?’ 

Our paper puts it best:
“Only when the scientific community prioritizes female health by including the variables that matter to female health will we begin to close the research gap between the sexes…Realizing the promise of precision medicine requires attention to how female-specific factors influence health outcomes.”  
 

CAMH enhances CARIBOU Pathway
for youth with depression

Gray Liddell has a unique perspective when it comes to the CARIBOU Pathway by CAMH for youth with depression. When the seven-step care pathway was in its infancy about four years ago, Gray was one of the very first participants. Then 16-years-old and struggling with depression, anxiety and OCD, Gray felt helpless and “grasping at straws” when they came to CAMH.

Four years later, Gray is now well enough to pursue a university degree in social work as well playing a key role at CAMH as a McCain Centre Youth Engagement Specialist and a co-creator of content for newer iterations of the CARIBOU Pathway.

“CARIBOU helped save me,” says Gray. “Throughout those 20 weeks it helped me slowly build up my resources and coping mechanisms. It was not a snap of the fingers, ‘oh my goodness everything is perfect’ kind of thing. But I realized that I can take care of myself and it’s going to be ok.”

CARIBOU is an evidence-based integrated care pathway (ICP) for adolescents with depression. It creates a roadmap for structured, multi-disciplinary care plans that map the treatment process from start to finish. By using CARIBOU, youth, their families and care providers can create clear treatment game plan that is evidence-

Treating Youth Depression on Multiple Levels

CARIBOU stands for “Care for Adolescents who Receive Information ‘Bout Outcomes”. The CARIBOU Pathway integrates seven components over a 20-week course of treatment for youth depression:

Co-designed by youth with lived experience of depression

“Youth engagement and co-design has been a major theme throughout,” says Dr. Courtney. “In order to be able to deliver effective care, we need to make sure it is delivered in a way that is relevant to youth, including the look and design of all CARIBOU clinical tools like handouts and videos, and Gray’s perspective having gone through the pathway has been very helpful.”

“My main goal here is just to make sure that youth voices are being heard,” says Gray. “Now that I am working with and beside the CARIBOU Pathway team I can see how far it has come and the progress it has made. Involving youth the way they have in this pathway makes me feel hopeful because there was a time when that wasn’t a thing and I’m thankful for that.”

Bridging the gap between research and practice for clinicians

As per best practice in clinical care, each component of the CARIBOU Pathway is based on the best available evidence. To support the effective delivery one of these components, the new CARIBOU CBT Clinician Training course for clinicians is planned for Fall 2023.

“It all comes down to the evidence and CBT is the first line treatment for young people with depression,” says Dr. Courtney. “Quite a few clinicians already have training in CBT, but there are several aspects to this course, including materials co-designed by youth, that will help clinicians deliver CBT in a way that is more engaging and effective for youth. We are also including a simulation aspect of this course to draw on the benefits of experiential learning.”

Other CARIBOU materials available to all clinicians via our website include:

• CARIBOU CBT Group Manual for Facilitators
• CARIBOU CBT Individual Manual for Facilitators 
• CARIBOU Integrated Care Pathway for Adolescents with Depression: Pathway Manual

Expanding the evidence

In order to measure the effectiveness of the CARIBOU Pathway, that is, the pathway components together as a package, Dr. Courtney’s team is currently conducting a study comparing outcomes for youth in the pathway to what is typically offered in the community. While the results of that study will not be available for a few more years, Dr. Courtney and his team hope that in the not-too-distant future, aspects of the CARIBOU Pathway will become the standard of care for youth with depression. The team also hopes that clinicians across Canada will be able to receive training in how to implement it well, possibly in the form of a CARIBOU accredited training program followed by a community of practice where clinicians can learn from each other about how to effectively deliver the pathway and troubleshoot in real-time.

Caring for CAMH patients and families

Annually, about 50 youth patients being treated for depression at CAMH receive treatment through the CARIBOU Pathway.

“We wanted to provide a bridge from what the research says is the best care and what is actually happening in the clinic,” says Dr. Peter Szatmari, Director of the Cundill Centre for Child and Youth Depression at CAMH, “By addressing depression in youth on multiple levels – including biological, psychological and social factors – we are trying to provide standardized, comprehensive and personalized treatment at the same time.”

CARIBOU offers a number of free resources for patients and families including

• CARIBOU: Flexible Care for Youth with Depression Video
• Mood Foundations Package for Youth
• Psychotherapy and YOUth: A Resource for Youth, By Youth
• Medication and YOUth: A Resource for Youth by Youth 
   

Ontario alcohol policy receives failing grade

CAPE Project finds Ontario score fell from top jurisdiction nationally to fourth overall at 40 per cent.

The Canadian Alcohol Policy Evaluation (CAPE) Project, released today its third and latest report evaluating alcohol control policies nationwide and in all 13 provinces and territories. Ontario scored a failing grade of 40 per cent, down from 55 per cent in 2019.

“Over the last several years, reductions in minimum alcohol pricing, extended hours of sale and expanded alcohol availability through take-out and delivery have all made alcohol more accessible both financially and physically, resulting in higher consumption, and ultimately more hospitalizations and alcohol-related deaths,” says Dr. Kevin Shield, Independent Scientist, CAMH Institute for Mental Health Policy Research.

“The Ontario provincial government is currently considering the sale of alcohol in convenience stores, which would be absolutely a move in the wrong direction,” says Dr. Leslie Buckley, Chief of the Addictions Division at CAMH. “We know that with the expansion of private outlets come increased alcohol consumption as well as healthcare costs and overall community harm. We’ve seen these harms play out elsewhere in Canada, notably in Alberta and British Columbia.”

“The good news for Ontario is that there’s a clear roadmap for us to do better,” adds Ashley Wettlaufer, CAMH Research Methods Specialist responsible for CAPE data collection, validation and analysis. “The recommended policies—such as refraining from further privatization and increasing minimum pricing—are achievable for Ontario, as most of them are already implemented somewhere in Canada. If we enacted all the current best practices that have been implemented across the provinces and territories we’d double our overall score and achieve an ‘A-’ or 80 per cent. Most importantly, it will result in less harm for Ontarians.”

The Ontario CAPE Project evaluation includes a detailed report card for our province which shows how we are faring in 11 different policy domains (including pricing and taxation, physical availability, control system, marketing and advertising, health and safety messaging and more) and offers tailored recommendations for how we can improve our scores and strengthen our policies in support of public health.

The CAPE Project is led by the University of Victoria’s Canadian Institute for Substance Use Research (CISUR) and brought together researchers from institutions across Canada to evaluate alcohol control policies and provide evidence-based solutions to improve health and wellbeing. The first CAPE report released in 2013 was led by CAMH and a team of 16 researchers. The second report was released in 2019 and led by the University of Victoria and CAMH.

Overall the results for Canada’s provincial, territorial and federal governments are quite poor. Every single jurisdiction got an overall failing grade, with the lowest scoring jurisdiction, Northwest Territories, only getting 32 per cent. The highest scoring jurisdictions—Manitoba and Quebec—only scored 44 per cent and 42 per cent, respectively. The federal government’s score was just 37 per cent.

The CAPE Project is a collaborative project involving researchers from CAMH, Western University, St Francis Xavier University, Dalhousie University, and the Canadian Institute for Health Information. All these institutions worked together to create the evidence-based scoring rubric, collect relevant policy data from across the country, and score the individual provincial, territorial and federal governments on how they fared across the 11 different policy domains. The project also relied on stakeholders within government to validate the data and ensure its accuracy.

The CAPE Project was funded by Health Canada and the Public Health Agency of Canada.

For full recommendations of evidence-informed principles to guide public alcohol policy in Ontario, review the CAMH Alcohol Policy Framework.

Click here to view the CAPE Ontario Report Card. 
 

Buzz-worthy News

• Women’s health research lacks funding. Conditions that affect women more than men garner less funding. But boosting investment could reap big rewards. Review the interactive infographic published by Nature here. 
• New commentary by CAMH researchers Drs. Sean Kidd and Kwame McKenzie in The Lancet argues that adequate shelter is crucial for addressing climate change risks on human health and meeting COP27 commitments, as it reduces health risks and supports vulnerable communities.
  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00722-5/fulltext
• A new CAMH-led meta-analysis examined the effects of alcohol taxes, minimum pricing, and limited availability on alcohol consumption - pricing policies and limited availability can help reduce alcohol consumption, especially for low-income users. However, there is a lot of variation between studies that must be considered.
  https://www.sciencedirect.com/science/article/pii/S2589537023001736

• Deep dive into the complexities of leveraging data strategy in public healthcare - listen to the podcast interview with KCNI Director of Operations, David Rotenberg:
  https://player.captivate.fm/episode/d09564bb-fc60-4742-8bc3-116dfc12359e