For many years science took a fatalistic point of view regarding our capacity to escape from neurological and psychiatric disorders like Alzheimer’s disease, stroke, autism and schizophrenia.

Yet research now reveals that many of the neuropsychiatric conditions that we acquire can be altered through our personal experiences. Nobel Laureate author Doris Lessing challenged us to live up to our greatest potential, which she described as our “beautiful, impossible blueprint.” Lessing appreciated that we all inherit a genetic plan from our parents but still have immense capacity to influence who we become. Our genes might tilt us in one direction, but our experiences, environment, and actions can dramatically change the journey. Lessing’s prescient observations, made more than half a century ago, predicted exciting research being performed by the dynamic neuroscience community at UBC, research that is featured in this special edition of Pathways.

Our genes might tilt us in one direction, but our experiences, environment, and actions can dramatically change the journey.

I worked in the neuroscience laboratory of Drs. Edith and Patrick L. McGeer, during the summer of 1974 before beginning medical school at UBC. This remarkable and visionary couple founded the UBC Division of Neuroscience while studying how the chemicals in our brain determine health and disease. Their grand vision helped to make UBC the leader that it is today. While the McGeers studied genetically determined processes, this couple also knew that environment was critical for our brain function. Pat was not only a scientist, but he was also a superb athlete who passionately exercised while railing against the influence of drugs and environmental toxins on the brain. The McGeers believed that science could cure neuropsychiatric conditions, and after one summer with them, I was hooked. After completing medical school and internal medicine training at UBC, I became a neurologist who studied and cared for people with neurodegenerative disorders like Alzheimer’s disease.

That’s why, in this edition of Pathways, I was heartened to read about the remarkable programs at UBC that explore how genes and the environment shape, change and restore brain functions across the lifespan. In aging research, we have learned from studying the genetic forms of neurodegenerative disease that the genetic blueprint is not the only factor predicting disease. While genes play a role in determining risk for Alzheimer’s and Parkinson’s disease, they don’t dictate their inevitability. Low education, head injury, lack of physical activity, smoking, drug abuse, hypertension, obesity, diabetes, hearing or vision loss, loneliness, air pollution and high cholesterol all increase that risk.

Today, even a person with a genetic predisposition for dementia is able to delay or even prevent its onset by making healthier choices throughout their lifespan.

Recent work from our group at University of California-San Francisco has found that even mildly low levels of vitamin B12 dramatically slow brain function and increase the protein tau which is associated with Alzheimer’s disease. In studies of superagers with high cognitive function we found that elders who exercised were more likely to fall into the group with superior memory and executive function. In another study, exercise seemed to protect people who carry genes that cause frontotemporal dementia.

Today, even a person with a genetic predisposition for dementia is able to delay or even prevent its onset by making healthier choices throughout their lifespan. Many of the risk factors for neuropsychiatric conditions fall disproportionately on low-income groups and Dean Dr. Dermot Kelleher has made the UBC Faculty of Medicine a leader in addressing these social determinants of health across the province. Social policy supported by great research can prevent disease!

At UBC, groundbreaking studies from neurologist and neuroscientist Haakon Nygaard probe how our brains adapt and respond to stress during the aging process. Aging itself increases susceptibility to neurodegenerative conditions but Nygaard explores the concept of brain resilience, studying how the brain can “bounce back” from damage or adversity. What’s exciting about Dr. Nygaard’s work, is that, by illuminating the underlying mechanisms of brain resilience, he and his colleagues could unlock new preventative treatments for diseases like Alzheimer’s and Parkinson’s.

Dr. Mark Cembrowski’s lab focuses on memory formation and its connection to emotion, particularly fear. Understanding how memories are created, stored, and retrieved in the brain is crucial for a multitude of disorders including Alzheimer’s disease, where memory is lost, and post-traumatic stress disorder (PTSD), where frightening memories are constantly relived. Cembrowski’s discovery of ‘ovoid’ memory cells that participate in these processesoffers a target for treatment and new avenues for addressing cognitive symptoms of PTSD, autism spectrum disorder (ASD) and epilepsy. As we better understand the specific cells that are targeted with neurological disease we can begin to study the unique genetic characteristics that make them vulnerable and develop therapies that protect them. Gene replacement therapies using CRISPR technologies are being used to treat diseases like sickle-cell anemia and similar efforts will soon begin with diseases of the brain. 

Our brains determine who we are and what we accomplish, yet we have the capacity to change our brains.

Meanwhile, UBC’s Dr. Steven Miller, along with colleagues at the BC Children’s Hospital Research Institute, reveals that early interventions, such as pain management, infection control and proper nutrition, significantly impact recovery after brain injury. Pain management, in particular, is crucial for preterm infants as unaddressed pain can disrupt brain connectivity during a critical period of development. Early-life brain injuries, once considered permanent with fixed outcomes, are also influenced by environmental factors that determine how our brains develop and recover over time.

It’s inspiring work — as is Dr. Annie Ciernia’s research into the cellular basis of ASD focusing on the interplay between genes and the environment. She is determining how factors like air pollution, inflammation, and even prenatal stress might alter gene expression during early brain development leading to or worsening ASD.

I never cease to be amazed by how far brain research has advanced since my days as a medical student, and how quickly it continues to progress. The UBC Faculty of Medicine is a leader in the emerging brain revolution that will bring therapies to conditions that were once considered untreatable. The tools becoming available for neuroprotection run from simple lifestyle changes like exercise, to harnessing genetic and molecular therapies that will bring basic science discoveries into to the clinic. Our brains’ determine who we are and what we accomplish, yet we have the capacity to change our brains. Through research, UBC scientists are improving neuropsychiatric health in the province and across the world. Stay tuned!

Dr. Bruce Miller holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Neurology at the University of California, San Francisco (UCSF) and directs the UCSF Memory and Aging Center.