CHU scientists use different types of neuroimaging, including MRI, to explore structural and functional brain alterations associated with the genetic mutations that lead to neuropsychiatric conditions.Credit: Sergey Ulanov
Two eight-year-old classmates may be similar by all appearances. But genomic testing, brain imaging and psychological testing may show that one child is predisposed to mental health and/or substance use issues that will likely become problematic during their teenage years, while the other child isn’t.
If the at-risk child undergoes a tailored cognitive behavioural therapy-focused intervention in late childhood, that exposure might be enough to change their neurodevelopmental trajectory.
The stakes are high: neurodevelopmental and psychiatric disorders are leading causes of disability in Canada. Genetic and social factors are both determinants of whether a child develops a neurodevelopmental or mental health condition, and the right intervention, at the right time, could modify or ‘rewire’ the child’s genetic and environmental risk. Such interventions are central to the work at Centre Hospitalier Universitaire (CHU) Sainte-Justine in Montreal, Quebec: the largest mother-and-child centre in Canada.
Experts in different neurological disciplines at CHU Sainte-Justine Azrieli Research Centre are joining forces through Centre IMAGINE, a new center for multimodal pediatric brain assessment, to explore the genetic, environmental and social determinants of mental health and develop interventions to alter the developmental trajectories of predisposed children and teenagers.Taken together, the work of clinical psychologist Patricia Conrod, medical geneticist, Sébastien Jacquemont, and computational neuroscientist, Guillaume Dumas, illustrates this new paradigm of precision psychiatry.
“Our institution is focused on understanding brain development and psychosocial health, along with deep biomedical expertise in related conditions,” says Conrod. “Together, we bring real strengths in understanding the evolution of mental health and psychosocial functioning.”
Personality-targeted interventions
Between 10 and 12 years, children start to develop traits that become increasingly predictive of later behavioural and mental health issues, Conrod explains. “I identify and validate these traits to understand how they're involved in predicting psychological disorders. But I'm also a clinical psychologist, so everything I do gets translated into novel and validated interventions.”
In 2009, Conrod and her colleagues developed the Substance Use Risk Profile Scale1, which identifies where children fall on four key personality elements: anxiety sensitivity, impulsivity, negative thinking and sensation seeking. A high reading on one or more of these attributes suggests an increased risk of a mental disorder, such as schizophrenia and substance abuse2.
Children participating in a PreVenture school-based programme session.Credit: © Dr. Patricia Conrod
The practical application of this scale and related neuropsychological profiles was PreVenture, a school-based programme, also developed by Conrod, that introduces cognitive behavioural interventions to children, tailored to their personality style. The workshops are designed to help students learn useful coping skills, set long-term goals, and channel their personality traits towards achieving them.
“We can use these cognitive behavioural strategies to help children better manage their psychological and biological risk,” Conrod says. “Our randomized trials have shown that we can reduce the likelihood of a young person transitioning to early-onset substance misuse by almost half3.”
Focusing on how personality and behaviour correlate with future mental health is just one route to developing tailored therapies. Exploring the biological basis of mental and neurodevelopmental health is another: that’s where the work of medical geneticist, Jacquemont, comes in.
Understanding biological risk
Jacquemont works to understand why specific genetic profiles put children at a higher risk of autism, schizophrenia or other neuropsychiatric conditions. This knowledge is critical to establishing early interventions and developing therapies tailored to patient needs.
Because genetic testing is routinely offered at the hospital, acquiring the data is easy: “Sainte-Justine clinicians use genome-wide sequencing to identify genetic mutations in children with a neuropsychiatric condition, resulting in a diagnostic yield of 10-40%,” says Jacquemont.
The next step is understanding how genetic variants lead to mental and neurodevelopmental disorders. Magnetic resonance imaging (MRI) and other types of neuroimaging have allowed Jacquemont and his team to gain insights into the structural and functional brain alterations mediating the risk conferred by genetic mutations. “With the new, very large datasets, we can then start describing some of the brain alterations associated with these mutations,” he says.
In a 2023 paper, Jacquemont and colleagues found that there are parts of the brain making many connections with other brain regions that are particularly vulnerable to multiple different genetic variants increasing the risk for psychiatric conditions4. “Now I have a mutation associated with psychiatric diagnoses, and I have the same mutation associated with a brain abnormality,” says Jacquemont. “The brain abnormality could be mediating this increased risk for a psychiatric condition.”
Such discoveries could refine diagnosis and treatment protocols, Jacquemont explains. Both genetic and neuroimaging information will likely help clinicians stratify patient groups to understand and predict outcomes and eventually apply tailored treatments.
“We're seeing more and more of these associations, and we are trying to understand the mechanisms,” he says. For computational neuroscientist, Dumas, advances in computational psychiatry mean that answers to mechanism questions like these and others may be within reach.
Hyperscanning for synchrony
Hyperscanning EEG helmets study human-human interaction, particularly in people with autism spectrum disorders, by recording the brain activity of several interacting people.Credit: CHU Sainte-Justine Foundation (Geneviève Charbonneau)
“We can now integrate different streams of data and levels of observation to go from inferential analyses to predictive models,” says Dumas. “Essentially, my team is trying to develop precision psychiatry.”
Underpinning Dumas’s work is the belief that all neuropsychiatric conditions have a social component, whether as a cause, consequence or mediator. “For conditions like autism where the social aspect is so important, having data about how the brain works during interaction is extremely valuable,” he says.
Enter hyperscanning: simultaneous multiple-person brain recordings. “I discovered we can observe inter-brain synchrony during social interaction,” Dumas says. “Just as different structures within one brain synchronize to integrate information during cognitive tasks, the brain activity of two people who are interacting synchronizes down to the millisecond.”
Dumas developed a series of portable, wireless electroencephalogram helmets and a multi-recording platform to log the brain activity of children, parents and even the clinician during a clinical interview.
“The growing area of multi-brain neuroscience may lead to transformative applications in psychiatry, from inter-brain measures for clinical characterization to inter-brain neuromodulation for treatments,” he says. “In effect, we’re finally able to invite neuroscience into the clinic5.”