Interview with Dr. Martin Alda: How genomics can lead to better outcomes for those with bipolar disorder

Published: February 13th 2019

Interview with Dr. Martin Alda: 

How genomics can lead to better outcomes for those with bipolar disorder

Dr. Martin Alda (R) and Dr. Rudolf Uher Photo Credit: David Grandy

Two psychiatrists at Dalhousie University and the Nova Scotia Health Authority (NSHA) have plans to apply genomics to the development of some much-needed clinical tools for the early detection and treatment of bipolar disorder. Success could bring significant improvement to the lives of those with the condition.

Dr. Martin Alda, the Killam Chair in Mood Disorders at Dalhousie, and Dr. Rudolf Uher, Dalhousie’s Canada Research Chair in Early Intervention in Psychiatry have received $975,000 to pursue their goal in a three-year research study, which started in early 2019.  The two psychiatrists also run successful research programs with NSHA.

Their project, Early Detection of Bipolar Disorder and Optimized Selection of Long-term Treatment, will take a personalized approach, using genomics to develop new screening tools and fast-track treatment for individual patients. Led by Genome Atlantic, the project has the support of a wide-range of financial backers, including Genome Canada, the Research Nova Scotia Trust, the Nova Scotia Health Authority, the Dalhousie Department of Psychiatry and the Dalhousie Medical Research Foundation. The number and diversity of their sponsors indicate the importance being placed on their work.

Nova Scotia has one of the highest rates of psychiatric disease in the country. In the world of mental illness, bipolar disorder is rated one of the top 10 causes of disability.

Current methods of diagnosis and finding the right individualized response, which usually involves long-term medication, are time-consuming. Delays can impair results, which are known to improve with early detection and treatment.

Drs. Alda and Uher hope to overcome those hurdles to achieve better outcomes by leveraging the role genetics plays in some key features of bipolar disorder, including causation, the risk of suicide and the response to long-term treatment. Using this knowledge, the plan is to achieve better patient results by developing clinical tools for early diagnosis and treatment. They anticipate their work could shorten the time from diagnosis to effective treatment by at least 12 months.

Genome Atlantic spoke with Dr. Alda recently to shed more light on their project:  

Genome Atlantic: What exactly is bipolar disorder and how debilitating is this condition?

Dr.Martin Alda: Bipolar disorder is a serious psychiatric illness, previously known as manic-depressive disorder. It typically affects young people and runs a lifelong course characterized by episodes of mania and depression. Bipolar disorder is often disabling, ranking among the top ten causes of morbidity worldwide. People with bipolar disorder are at risk of increased mortality due to suicide but also from various physical causes such as heart disease or diabetes. The manic and depressive episodes can be prevented by suitable long- term treatment, but not all people respond to the same treatments and choosing the right medication by trial and error is a lengthy and frustrating process.

Genome Atlantic: How common is bipolar disorder in Nova Scotia?  In Canada?

Dr. Martin Alda: Bipolar disorder affects about 2 per cent of all adults in Canada (and Nova Scotia).

Genome Atlantic: How is the condition commonly diagnosed now, and what are the drawbacks with this process?

Dr. Martin Alda: Bipolar disorder is typically diagnosed based on clinical symptoms. In the early stages, the illness is often difficult to differentiate from other psychiatric conditions such as major depression or schizophrenia. This uncertainty of diagnosis means that many patients are diagnosed properly only after a delay of several years. It is during this early stage of illness when timely treatment can make the most difference in the illness outcome.

Genome Atlantic: What are the genetic links to bipolar disorder and how long have we known about them?  What are the odds that people with these genes will go on to develop bipolar disorder?

Dr. Martin Alda: A number of studies have established that bipolar disorder is heritable and that the genetic factors account for up to 80-85 per cent of the overall risk of the illness. Several genes have been discovered that increase the odds of developing bipolar disorder, but more work is needed to clarify how these genes in combination with non-genetic factors predispose people to develop bipolar disorder.

Genome Atlantic: Since this project will be breaking new scientific ground, perhaps you could explain what made you think of using these genetic links to try and develop methods for earlier detection and better treatment for bipolar disorder?  Was there a Eureka moment when you came up with this project?

Dr. Martin Alda: From work of several research groups including our own work, we know that genetic factors play a role in the risk of bipolar disorder and that they are an important factor in determining who responds to what kind of long-term treatment. Thus, it is a logical step to start looking at the risk genes and their combinations to come up with a set of factors that will guide clinical decisions.

Genome Atlantic: Can you describe the new clinical tools you aim to develop?

Dr. Martin Alda: We plan to use a combination of clinical measures and genetic information from the entire human genome. Ultimately the tool should provide a guide to clinical features relevant to the risk of illness and/or the likelihood of responding to a particular medication and combine these with the genetic factors.

Genome Atlantic: How do you foresee these new clinical tools changing diagnosis and treatment of bipolar disorder?

Dr. Martin Alda: Our proposal falls under the now much-talked-about concept of precision medicine. Most areas of medicine including cancer treatment or cardiology are moving towards tailored treatments based on individual patient characteristics rather than one prescription fitting all.

Genome Atlantic: What benefits would they bring to patients and their families?

Dr. Martin Alda: Our hope is that the improved treatment will reduce the risk of the illness and will shorten the time to an effective treatment selected to fit the patient’s clinical and genetic profile.

Genome Atlantic: This project is a three-year endeavor so can you briefly outline what you intend to do over that period?

Dr. Martin Alda: Most of the work is to be done here at Dalhousie and in the Nova Scotia Health Authority. Exactly speaking, it is not a three-phase project, but some parts of it will take a full three years (and possibly longer). Our proposal has several aspects and some are closer to clinical applications than others. We expect that any new discoveries and decision tools will need to be further tested before being implemented in clinical practice.

Genome Atlantic: If you succeed in developing these new genomic diagnostic tools, how soon could Nova Scotians expect to see them adopted for general clinical use?

Dr. Martin Alda: We expect that at least some of the tools will be ready by the end of the project; some may take longer.

Genome Atlantic: Are there other psychiatric disorders where you think genomics could provide the keys to better diagnosis and earlier or better treatment?

Dr. Martin Alda: Not only bipolar disorder but other forms of severe mental illness such as schizophrenia or depressive disorder.