Toronto Star

Research that’s changing lives

DNA analysis, advanced MRIS offer insights into the brain and less invasive treatments

- SHARON ASCHAIEK SPECIAL TO THE STAR

Increasing­ly powerful tools for detecting and treating mental illness are significan­tly improving research and patient care at the Centre for Addition and Mental Health.

One of the most useful pieces of technology at CAMH determines how patients will react to psychiatri­c drugs. The DNA variant analysis machine can examine a patient’s saliva sample for genetic difference­s that might make them susceptibl­e to side effects.

This work used to be performed by two machines that processed one sample a day at a cost of $1,000 each. It also took a week to churn out results. The new all-in-one model, introduced a year ago, can analyze 10 samples a day at a tenth of the cost and provide answers the next day.

“The process has become more efficient and economical, which allows us to do research at a faster pace,” says Dr. James L. Kennedy, director of the Neuroscien­ce Research Department at CAMH, the first psychiatri­c facility in the world to use the machine.

Kennedy’s work focuses on pharmacoge­netics, an area of personaliz­ed medicine that investigat­es how genetics influence responses to psychiatri­c medication­s. His research has identified a new genetic risk factor that explains why some schizophre­nic patients gain excessive weight on certain drugs. Prescreeni­ng for genetic risk factors reduces the trial and error in finding the right drugs for patients, Kennedy says.

This summer, CAMH will be the first psychiatri­c facility ever to receive a DNA sequencing machine, which can examine single DNA molecules in the genes that react with psychiatri­c drugs. This testing will reveal how people of different ancestries respond to different medication­s, making it possible to create individual­ized drug regimes.

As well, Kennedy is working to make personaliz­ed medicine mainstream through “lab-on-a-chip” biotechnol­ogy that would allow patients to easily share their genetic risk data with health-care providers.

“They could store their genetic informatio­n on their smartphone or on a chip and provide it to their doctor, or have it on hand at an ER if they ever need emergency medicine,” Kennedy says.

A different kind of technology at CAMH is shedding new light on the causes and possible cures for Alzheimer’s disease. The advanced magnetic resonance imaging (MRI) machines at the new Research Imaging Centre have helped Dr. Aristotle Voineskos detect a critical gene variation that’s involved in both promoting learning and memory and in predisposi­ng the brain to the disease.

In a study of 69 healthy participan­ts, Voineskos used diffusion MRI, which shows the tiniest details of biological materials, to study the gene, called brain-derived neurotroph­ic factor, or BDNF. In brains with a BDNF variant, he could detect subtle but important difference­s in memory-related architectu­re, including in cortex thickness and white-matter connection­s.

At the same time, this gene produces a vital protein that enhances the brain’s plasticity, or ability to learn new things. “With this gene variation, there is a link between the risk it poses and the treatment it could offer. If we can figure out how to finetune BDNF expression in the brain, it may help people at risk of Alzheimer’s,” Voineskos says. The brain changes caused by this variant take years to occur, making it possible to determine if someone has a predisposi­tion before full-blown Alzheimer’s hits. This long gap between initial signs and full-blown symptoms provides a window of opportunit­y for Voineskos to research how to use this memory-aiding gene to delay and, ideally, treat Alzheimer’s. “With the imaging machines we have, we can go beyond the highways of the brain and permeate the roads or streets to get a more refined understand­ing of how the brain is connected,” Voineskos says. Technology at CAMH is not only helping researcher­s better understand mental illness, but offering less invasive treatment options. A perfect example is repetitive Transcrani­al Magnetic Stimulatio­n, or rTMS, an interventi­on CAMH doctors have been using since the early 2000s to treat depression and schizo- phrenia. The approach involves uses a magnetic field to deliver a weak electric current to targeted sites in the brain.

“It activates brain cells and can help with improving plasticity. It achieves really good results with many patients,” says Dr. Jeff Daskalakis, director of the Brain Stimulatio­n Research and Treatment Program at CAMH, which was the first psychiatri­c centre in Canada to use rTMS for mental illness.

Previously, the only type of brain-stimulatio­n treatment for mental illness was electrocon­vulsive therapy (ECT), which involves electrical­ly inducing seizures to promote healing. While it can work —Daskalakis says there is about a 30-per-cent higher response rate to ECT over rTMS—it produces nasty side effects such as migraines, nausea, memory loss and seizures. As well, patients must be anaestheti­zed during a procedure.

By contrast, rTMS has few to no side effects and patients can stay awake throughout the process.

“Even though ECT is more effective, many patients don’t want the endless courses of seizures in their brain,” Daskalakis says. “rTMS gives them another option.”

 ?? SALVATORE SACCO FOR THE TORONTO STAR ?? Dr. James L. Kennedy, left, director of the Neuroscien­ce Research Department at CAMH, focuses on pharmacoge­netics, an area of personaliz­ed medicine that investigat­es how genetics influence responses to psychiatri­c medication­s.
SALVATORE SACCO FOR THE TORONTO STAR Dr. James L. Kennedy, left, director of the Neuroscien­ce Research Department at CAMH, focuses on pharmacoge­netics, an area of personaliz­ed medicine that investigat­es how genetics influence responses to psychiatri­c medication­s.

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