*Names have been changed.
“It’s been absolute hell,” Sara* says of the depression that has ripped through at least five generations of her family. Her great grandmother killed herself at the age of 35. Her grandmother ended her own life in 1988, after suffering for decades. Her great aunt spent 40 years in a German asylum, shunned from society for her depression. Her uncles, cousins, and children have all suffered from mental health issues. When her mother in Kamloops, B.C., suddenly started showing signs of major depressive disorder at age 60 — transforming from an outgoing, loving wife, mom and grandma to a hardly recognizable, dependent, low-energy “shell” — Sara says her life was turned upside down. Her mom was deeply sad, rapidly losing weight and needed Sara’s constant company.
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“That’s when the nightmare really started, not only because we all knew what my mom had was obviously depression, but because we had to spend the next five years figuring out what treatment would actually make her better,” Sara says. The trial and error of trying different drugs and therapies while her mother languished was almost worse than the condition itself, she says.
Sara’s mother finally found the treatment that worked for her: electroconvulsive therapy, or ECT. She improved, but over the next two decades, depression resurfaced many times — and since ECT was viewed as a last resort, the cycle of experimenting with treatments would start again: different medications, increasing and decreasing dosages, sometimes combining two or three different drugs.
This approach to treating depression has been the standard practice for decades: Doctors take their best guess, prescribing medicines or therapies to suffering patients and seeing what sticks.
But thanks to the effort of a team of connected mental health experts across the country, this may be about to change. CAN-BIND (Canadian Biomarker Integration Network in Depression) is a network of clinicians, data scientists, biologists and psychiatrists who are searching for ways to treat depression more acutely, by matching physical signs in the blood and in brain imaging to the right kind of treatment. The network has been working together since 2011, and now, with certain studies expected to cede results in the fall, the possibility of individually tailored therapies could soon be on the horizon.
“If you were diagnosed with breast cancer,” says Sidney Kennedy, the lead investigator for CAN-BIND, “your doctors would take all sorts of information — your genetic tests, the biopsy results, the stage of the disease,” and tailor a treatment program based on your specific case. “There would be a plan, one based on the data,” he says. Developing catered treatment plans like this for depression is the driving force behind CAN-BIND, which is funded largely by the Ontario Brain Institute.
“I would absolutely call it a revolution,” says Lena Quilty, a clinical psychologist and scientist at the Centre for Addiction and Mental Health in Toronto. She says changing the way depression is diagnosed and treated would radically change the landscape – including her own work, which finds benchmarks for how mental illness is measured. (CAN-BIND used some of Quilty’s work early on to help design their studies.) Roughly 600,000 Canadians seek out medical or therapeutic treatment for depression every year, she says. “So it would be a welcome revolution at that.”
For Sara, depression had come in waves throughout her childhood. But she only sought treatment three years ago, when “a tidal wave” of major depression hit, and she immediately recognized it for the possibly fatal illness that has plagued her family. The diagnosis: major depressive disorder, which, according to the Canadian Mental Health Association, affects about 8 percent of Canadian adults sometime in their lives.
“I should be happy, I remember thinking,” she says. “My daughter finally was getting better from a seizure condition. My other daughter was planning her wedding. I should have been over the moon… But there I was, 55 years old and thinking of killing myself.” The thought of having to endure the endless cycle of drugs and therapies in order to finally find a functional treatment terrified her — she knew that the longer the depression weighed on her, the worse the outcome could be.
Sara found out about the CAN-BIND research and, eager to avoid the shot-in-the-dark cycle her mom experienced and “hopefully find something that would help lift the fog,” she joined CAN-BIND’s first major study, one that spanned six cities: Vancouver, Calgary, Toronto, Hamilton, Kingston, and Halifax. The study, called CAN-BIND1, examined how people with depression on specific anti-depressants, at specific dosages, responded to their treatment, while carefully monitoring participants’ clinical symptoms, blood tests and brain imaging. The data from the first stage of the study is currently being analyzed; next, the team will develop a hypothesis about what treatments works most effectively for specific symptoms and bio-markers.
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“We’re trying to subcategorize the disease,” says Dr. Kennedy. “This is our chance to refine, rather than to completely tear up, the question of how you diagnose and how you treat mental health conditions. This is precision medicine, precision psychiatry. We begin to see ways to re-conceptualize mental illness.”
While the researchers don’t yet know the end result of this first study, Dr. Kennedy says that “right now we are being close to being able to say depression, as a clinical disorder, comes in various shapes and sizes.” The team has already had success looking at MRIs and the influence of chronic inflammation on certain areas of the brain, and Dr. Kennedy says they are developing theories on those abnormalities as markers for depression.
The researchers are currently trying to identify subtypes of patients in CAN-BIND 1, which will then allow them to look at their responses to treatment. By October, Dr. Kennedy says, the picture will be clearer.
It’s not just the data being collected that is revolutionary, but how the data is being analyzed. The team is using artificial intelligence, or what’s known as “machine predicting,” to examine all of the various elements — clinical symptoms, genetics, brain scans, blood tests — to come up with a singular picture of a depressed person, called a biosignature.
“With our machine approach, we hope to be able to find a type of depression that responds particularly well to a specific treatment,” says Dr. Raymond Lam, who oversees CAN-BIND’s clinical program and is a professor of psychiatry at the University of British Columbia. The use of artificial intelligence differentiates this study from others that have looked for physical signs of depression in the past, he says. “AI means that we’re able to look at so many variables at once — type of symptoms, genetic markers, brain scans. Depression is so variable, so this is so important.”
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The team has also put a lot of energy and time into determining what blood tests can specifically tell them about someone’s depression. Dr. Jane Foster, scientist at St. Michael’s hospital in Toronto and the co-lead of the molecular program at CAN-BIND, explains that the DNA found in a patient’s blood is important, but so too is the blood’s information about how the environment impacts our DNA. Twins, for example, can have identical genes but, with different environmental influences, suffer different conditions. “There are also inflammatory markers in the blood that are a response to environmental stress or trauma, and may be an indication of depression itself,” Dr. Foster says.
Every depression treatment option works well in roughly 50 to 60 percent of patients, says Dr. Lam, and over the next six months, he hopes to come closer to figuring out which physical signs will best line up with which treatment. “In the future,” says Dr. Lam, “we hope to be able to use relatively simple means — that’s a blood test, questionnaire, and brain scan, and we’ll be able to predict for a particular person whether a treatment is going to be successful.”
With the cross-Canada effort, using advanced technologies and a dedicated, passionate team, Dr. Lam says, “We’re narrowing in — and I think we’ll find something. We have to.”
For Sara, who reacted positively to medication while in the CAN-BIND study, the advancements are wildly exciting. “I’m very happy to have been a guinea pig for them,” she says with a laugh. “I’m determined to protect my children from the experience of my grandmother, my cousins, my aunts and uncles, and my mother… If my daughters don’t have to go through the garbage that we all had to go through, finding the right kind of help, that’s our family’s future, and it’s bright.”