Decoding the effects of early life adversity on mental health

While it is commonly understood that a difficult childhood can lead to mental health issues, research has now exposed deeper, more troubling impacts of early life adversity: that these experiences can reshape the brain and body at a cellular level. Physiological effects like these are at the core of the McGill-Douglas-Max Planck Institute of Psychiatry International Collaborative Initiative in Adversity and Mental Health (AMH Initiative). This five-year, $5M project, made possible in part through funding from McGill’s Healthy Brains, Healthy Lives, seeks to uncover the biological roots of mental illness, the leading cause of disability worldwide. The international team is now working to expand research in the area, support the next generation of researchers and, ultimately, enhance prevention and treatment for the public.

“The AMH Initiative brought together two leading centres on the study of the impact of early-life stress on behavioural and emotional development and fostered important collaborations between several McGill and Max Planck Institute Labs, as well as with other universities,” said McGill’s Dr. Gustavo Turecki, Canada Research Chair in Major Depressive Disorder and Suicide. Dr. Turecki co-leads the initiative alongside Dr. Elisabeth Binder from the Max Planck Institute of Psychiatry (MPIP) in Munich, Germany.

The AMH Initiative lays the foundation for potential long-term impacts on clinical practices and treatment strategies by focusing on basic research, understanding mechanisms and increasing knowledge through innovative pilot projects, monthly meetings, exchange programs and collaborative efforts.

Molecular changes

The heart of the initiative lies in better understanding psychiatric disorders, such as depression. The Public Health Agency of Canada reports that some 13 per cent of Canadians will experience depression in their lifetime, with only one in three cases responding to anti-depressants. Persistent depression can have catastrophic consequences, given approximately 12 Canadians die by suicide each day.

Through this initiative, collaborators Dr. Turecki and Dr. Jan Deussing from the MPIP are investigating the molecular factors that influence the effectiveness of anti-depressants. Their study has revealed that depression does indeed cause molecular changes at the cellular level, but these molecular changes can be reversed in response to anti-depressant treatment. The team is now planning to delve more deeply into the underlying mechanisms of these changes through additional research.

Building on strengths

Since its inception in 2021, the AMH Initiative has evolved to really leverage the unique strengths of the Douglas Research Centre and the MPIP. According to project coordinator Germaine Lowe, the union between these two state-of-the-art institutions, considered powerhouses in the fields of psychiatry and mental health research, will propel scientific discovery.

“It is exciting to have a concrete opportunity to build on our strengths and existing collaborations,” said Lowe. “This allows us to solidify partnerships and provide access to these facilities and datasets that would not otherwise be accessible to, say, early-career researchers.”

Jose Maria Restrepo is one such early-career researcher at McGill. Having recently defended his PhD successfully, Restrepo studies how adversity in adolescence might affect the genes responsible for the development of the prefrontal cortex, potentially contributing to mental health disorders in adulthood. As part of the AMH partnership, Restrepo visited the MPIP in the winter of 2023 and raved about the opportunities afforded by this exchange. “It was a pivotal moment for me to work next to people I admire and use technologies I could only have dreamed of,” he shared. “It allowed me to take past projects out of the dust and revisit them with entirely new perspectives.”

Promoting collaboration

The AMH Initiative has fostered many collaborations that favour exceptional learning and exchange experiences over a typical, more competitive research environment. While investigating the association between early life adversity, insulin signaling and executive function, McGill Neuroscience PhD graduate Aashita Batra attended an AMH monthly meeting that changed the course of her research. A student at the MPIP presented a method that answered challenges in Batra’s own research, and with support from her supervisor Dr. Patricia Pelufo Silveira, she wrote a proposal that led to a collaboration and a month-long exchange in Munich.

“Research can sometimes be so competitive, but this environment promotes sharing ideas and techniques. The goal is to move science forward through collaboration,” she explained. Batra also said that the experience enhanced her science communication skills and facilitated her professional development as a medical writer.

Bringing the team together

To heighten this spirit of camaraderie and partnership, the international team held a retreat in March 2023 to bring together researchers from both institutions in the Bavarian Alps. “It was invigorating to meet outside of a Zoom setting,” Lowe said. “We spent the first year and a half of this project online, so this opportunity brought people together and deepened the dialogue.”

Restrepo shared the same enthusiasm, having combined his exchange with the retreat. “It was one of the highlights of my life. Psychiatry is a complex field, so sharing and learning from each other’s research and day-to-day life was mind opening.”

In just two years, the AMH Initiative has doubled interactions between researchers across the two institutions —a testament to its capacity to transcend borders and foster international collaboration. While clinical applications might still be a distant goal, Lowe emphasized that collaboration is the starting point.

“The knowledge gained from fundamental, basic research like this lays the groundwork for future breakthroughs in mental health research,” she said. “An international program of this scale serves as an example for the amazing work that is possible when we favour collaboration over competition: it allows the scientific community to better understand mental illness, and in turn, provide better support.”