Exploring the brain-gut connection in mental health

An interview with Dr. Margaret Hahn

Article by Sally Wu

Graphic design by Amy Assabgui

Trillions of living microorganisms reside in pockets of bustling communities in the human body. An array of bacteria, viruses, fungi, and other microbes collectively form microbiomes—the microbial inhabitants that contribute to human health and well-being. Ongoing efforts by scientists to characterize the functions of microbes, specifically the gut microbiome, have discovered its tremendous impact on metabolism, the immune system, the heart, and other important physiological functions.1 We are only now beginning to understand and acknowledge the importance of having a healthy gut microbiome and its role in health and disease. More recently, studies have suggested that the gut microbiome may also affect mental health.2 Dr. Margaret Hahn (along with Dr. Daniel Mueller), their team at the Centre for Addiction and Mental Health (CAMH), and their collaborators at the Farncombe Institute at McMaster University are leading translational studies to investigate the complex interplay between the gut and the brain. Their research aims to better understand the underlying mechanisms of the metabolic burden observed in patients with schizophrenia. 


Dr. Margaret Hahn
MD, PhD, FRCPC
Director of the Mental Health and Metabolism Clinic | Clinician-Scientist in the Schizophrenia Division at the Centre for Addiction and Mental Health | Associate Professor at the University of Toronto | Kelly and Michael Meighen Chair in Psychosis Prevention

Photo Credit: CAMH

Dr. Hahn completed her undergraduate studies in biochemistry and immunology at McGill University. She has always had an interest in metabolic pathways and how these may interact with the immune system. As she completed her MD at the University of Calgary, Dr. Hahn reminisced that “while I enjoyed medical school and seeing patients, I’ve always had the interest to discover novel things and to improve the care of patients. I always felt like the way to do that was through research.” As the “brain was a more undiscovered frontier…that has more potential for discovery and to further the care of patients”, she decided to complete her residency in psychiatry. She later completed her Doctoral degree at the Institute of Medical Science at the University of Toronto. “Thanks to Dr. Gary Remington who managed to convince me that on top of all these years of studies that a PhD was a good idea.” Dr. Hahn laughed and continued, “In the long run, it was a good idea because it gave me the background in not only psychiatry but [also] allowed me to focus on the metabolic comorbidity in schizophrenia.”

As the Director of the Mental Health and Metabolism Clinic at CAMH, Dr. Hahn expressed that “working as a clinician in this field has highlighted the lack of ability to improve patient outcomes in so many domains. This includes the huge gaps in physical care and addressing the high cardiovascular mortality rates that represent the leading cause of death in schizophrenia patients and other severe mental illnesses, [surpassing] suicide.” Even before patients with schizophrenia are prescribed antipsychotics, they present with premorbid metabolic dysregulation, particularly insulin resistance and dysglycemia.3 To make matters worse, antipsychotics additionally induce adverse metabolic side effects, such as insulin resistance, weight gain, and contribute to the very high prevalence of type 2 diabetes in patients.4 A potential culprit of this observed metabolic dysregulation is the gut microbiome. 

“There is a really complex interplay between the brain and body. We tend to treat each system separately. One of the systems that is linked to mental illness and most certainly a key aspect of metabolism is the gut microbiome,” Dr. Hahn explains. 

A few years ago, Dr. Hahn and Dr. Daniel Mueller along with other scientists in different areas of research at CAMH had the good fortune to receive a donation from the Farncombe family to ignite a collaboration between CAMH and the Farncombe Family Digestive Health Research Institute at McMaster University (Drs. Elena Verdu and Premysl Bercik) to conduct one of the first pilot projects examining the gut microbiome and mental health in Canada. Their interest and passion in the metabolic health of patients led them to create a proposal suggesting that the gut microbiome may contribute to the increased risk of pre-morbid metabolic dysfunction, as well as antipsychotic-induced metabolic dysregulation in patients with psychosis spectrum illnesses. This proposal has grown into a project that first started in humans but has now (through a successful Pilot and Feasibility funding competition from the Banting and Best Diabetes Centre) taken a backward translational approach into rodent models. In humans, antipsychotic-naïve patients are followed over twelve weeks to investigate the effects of pre-and post-antipsychotic treatment on metabolic functions. Basic metabolic panels are completed, and stool samples are collected. Weight and body mass index are also recorded to monitor for antipsychotic-induced weight gain, which occurs in a subset of individuals. The pre-antipsychotic treatment stool samples from the individuals who go on to gain weight are then transplanted to germ-free mice to examine the causality of these metabolic side effects. “The hope is that in the future we can find which gut microbiome signatures predispose patients to these metabolic side effects. Then we can intervene with probiotics in a subset of patients—a type of personalized medicine.”

“Taking a step back, our research focuses on schizophrenia, but all mental illnesses have a very large metabolic burden. The gut microbiome may explain some but not all of the interactions between the body and brain,” says Dr. Hahn. 

When asked to share the most important thing that the public should understand about the gut microbiome and mental health, Dr. Hahn emphasized that “you can’t separate physical and mental health, and the gut microbiome could represent a link between the two. Going forward, we can’t work in silos. Our field needs multidisciplinary collaborations from different specialties to address different aspects of a complex multisystemic illness in order to move to novel interventions. You can’t have a good quality of life or functional outcomes if you don’t have good mental and physical health.” At the end of it all, Dr. Hahn exuded gratitude and appreciation for her team, collaborators, mentors, study participants and the generosity of her funding sources and the Farncombe family, all of whom make this work possible and rewarding. 

References

  1. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015; 31(1):69-75.
  2. Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016: 21(6):739-748.
  3. Papanastaiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review. Ther Adv Psychopharmacol. 2013: 3(1):33-51.
  4. Rajkumar AP, Horsdal HT, Wimberley T, et al. Endogenous and antipsychotic-related risks for diabetes mellitus in young people with schizophrenia: a danish population-based cohort study. Am J Psychiatry. 2017: 174(4):686-694.