Population Neuroscience and Brain Health

Population Neuroscience and Brain Health: the promise of epigenetics

The field of behavioral epigenetics was launched in a foundational study by Dr. Michael Meaney and Dr. Moshe Szyf in 2004. This and subsequent studies established that childhood experience — such as emotional, sexual or physical abuse — can alter the individual genome and increase vulnerability to psychiatric and neurological disorders.

Doctor Michael Meaney

Dr. Michael Meaney
Director of the Program for the Study of Behaviour, Genes & Environment

“Simply by understanding and addressing risk factors, we managed to reduce heart disease by 75%. We’re targeting similar reductions in diseases such as depression, Alzheimer’s, Parkinson’s and anxiety disorders. We’re building the tools and the knowledge to make it happen.”

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Bridging the gap between genes, neuron cells and individuals

Understanding how mental illness manifests in the human brain often means starting with animal models. But not just any animal cell will work: developing models that accurately reflect results in humans is an ongoing challenge.

Doctor Brigitte Kieffer

Dr. Brigitte Kieffer
Scientific Director of the Douglas Institute Research Centre

“Understanding the biological causes of mental Illness is one of our greatest challenges for the coming decades. Neuroscience research in small animals opens the door to understanding brain disorders, and becomes truly powerful when integrated with human research.”

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Understanding the brain in its social context

Throughout our lives, our brains are shaped by our social environment. Social and cultural differences in infancy and childhood, as well as in everyday life settings, influence the risk of developing mental health problems. Understanding the brain in its social and cultural contexts is crucial for developing solutions for many pressing health and social concerns, including major inequities for some segments of our society.

Doctor Lawrence Kirmayer

Dr. Laurence Kirmayer
Director of the Division of Social and Transcultural Psychiatry

“The brain is the organ of culture — we are fundamentally social beings and our brains reflect our environments. McGill is deeply engaged in understanding the impact of cultural diversity so that we can apply new findings from neuroscience in ways that promote the resilience and wellbeing of individuals and communities.”

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HBHL's Proposal 

Why do some people thrive while others have mental illness? Brain health emerges through the constant interaction between gene networks and environmental influences, operating over time to shape neural circuitry in a context-specific manner. A clear understanding of individual variation in brain health requires integration of complex imaging, genetic, and environmental information, together with detailed metrics of function in real-world settings, akin to those of the National Institute of Health Toolbox.[1] Such studies must also occur within a framework that includes cultural influences and context. This approach has the potential to revolutionize the prevention, diagnosis, and treatment of mental illness and improve brain health across the population.

The integration of NeuroHub’s computational approaches into population studies provides the opportunity to define precision interventions that target individuals and not merely their circumstances. We will work with large longitudinal birth-cohort studies to define the genetic and environmental determinants of individual trajectories of vulnerability or resilience. Through CBRAIN, McGill is a hub for a network of 10 cohort studies in Europe, Asia, and North America that are a rich source of genetic, epigenetic, phenotyping, imaging, and social data on parents and children from the prenatal period to adolescence. This rich data will be fed into NeuroHub and supplemented by new information that HBHL will gather through novel technologies, such as web-based, direct-data capture, and database tools that can monitor and assess real-time function in real-world settings, like schools or homes. The result will be a detailed, multidimensional picture of what vulnerability to mental illnesses looks like in any individual, what confers resilience or risk, and what interventions can help stop these devastating conditions before they take root in adolescence and early adulthood.

Clinical psychiatry operates in the absence of objective markers on which to base diagnosis and predict treatment outcomes. Even common treatments for mental disorders are highly variable in their efficacy – helping some, but doing little for others. We will use depression, the most common mental disorder affecting more than 3 million Canadians, as the initial basis of our studies. Our depression studies will provide a model for a neuroinformatics approach to predicting treatment outcomes, mapping the functional, neural circuitry, genetic and epigenetic determinants of individual responsiveness. This will allow us to define subgroups of depressed patients who will respond to certain treatments.

The study of basic causal mechanisms of variation in brain function requires the use of animal models. We will use innovative technologies like optogenetics that permit manipulation of specific circuits, customized manipulation of rodent genomes, focused neuronal stimulation, electrophysiology, and neuroimaging in freely moving animals. By combining these approaches with the NeuroHub strategies of integrating data, we will be able to test hypotheses regarding the molecular mechanisms underlying these findings in patients and further validate the models generated from the human data.

 Outcomes: HBHL’s integrative model and the NeuroHub, combined with animal models and our strong networks of international cohort studies, will allow us to identify the basic mechanisms of vulnerability, resilience, and responsiveness to treatment, informed by context and culture. We will design new, improved interventions to prevent and treat mental illness in a culturally informed manner. Partnering with educators and industry, we will develop evidence-based programs that target school underachievement or dropout, address the specific mental health challenges of new Canadians, improve mental health in the workplace, and promote healthy living through supportive environments.

 

[1] www.nimh.nih.gov/research-priorities/rdoc/index.shtml