Dal researchers looking for genetic clues
“Bipolar disorder is treatable; many people can live well. There is hope,” says psychiatrist Dr. Martin Alda.
This may come as a surprise to people whose perceptions are shaped either by frightening stereotypes in TV dramas (which link the condition to murderers and lunatics), or by the sad facts behind obituaries for many young adults: that bipolar disorder claimed their lives before they knew what was happening to them.
Alda’s hopeful message arises from his 30 years of studying the condition, which used to be known as “manic-depressive,” because of a person’s mood swings between periods of extreme highs and lows. He and his colleague Dr. Rudolf Uher are at the forefront of new research at Dalhousie University. They are using genetics to diagnose bipolar disorder more quickly and to try to customize treatment for individuals. About 20,000 Nova Scotians are affected by bipolar disorder.
“Bipolar disorder carries the highest risk of suicide among all psychiatric conditions,” explains Alda, a researcher and clinical psychiatrist who holds the Killam Chair in Mood Disorders at Dalhousie.
“That’s because the risk of suicide is highest in the first few years of the illness, and the onset of symptoms is generally during the late teens and early adulthood.”
Alda says of the 130-150 suicides a year in this province, about 90 per cent involve a psychiatric disorder of some kind, a list that includes depression, schizophrenia, and bipolar disorder. “Early treatment cannot only reduce the risk of suicide, but there are data to suggest that if you can treat early, people will do better and live well.”
Johanna Begin, 51, is someone who is “doing well” and has taken medication for bipolar disorder for decades. She’s the mother of three grown children between the ages of 16 and 25, a community volunteer, and a foster parent. A severe post-partum depression after her first child sent her looking for psychiatric help.
“If it hadn’t been for my husband,” she says, “I couldn’t have put my feet on the floor. It would be six years before we had another child.”
Begin crashed again in her mid-30s, while simultaneously overseeing the construction of a new home, holding down a fulltime job at a bank, and raising three children under the age of nine. This time she was diagnosed with bipolar disorder.
“It was almost a relief,” Begin says of her diagnosis, “because then I knew I wasn’t crazy. I had symptoms that fit, and it wasn’t all in my head.”
Mental illness does run in families. Begin was initially helped by the same medication that had worked for her mother, whom she knew had spent time at the Nova Scotia Hospital. Her older brother has a more severe bipolar disorder. Her biggest concern now is how bipolar disorder or other mental health disorders will play out for her children, two of whom have already struggled with depression and severe anxiety.
Researchers say genetics play a significant part in predicting who is at greater risk. Children of parents with bipolar disorder have a 20-30 per cent risk of developing some type of mental illness compared to a 10 per cent risk for people with no family history.
“Genetically speaking, we see it all in my family: depression, anxiety, bipolar,” Begin says. “The outcome of this research may not help my children now, but it may help their kids later.”
Her hope is that there will be a blood test someday that would tell people if they have the gene for bipolar disorder so that they could be watchful and seek help early. That’s the case for cystic fibrosis and a certain type of breast cancer: if you have the specific gene, it means you will develop the disease. Unfortunately, it is more complicated when it comes to mental disorders. That’s when you get into probabilities.
Alda says at least 30 genes have been identified as contributing factors to bipolar disorder. The research he and others will undertake over the next three years is to track and identify the most frequent combinations and interactions among them. If successful, Alda and Uher believe they can shorten — by as much as one year — the current trial-and-error period to find an effective treatment that allows someone to live a normal life.
For Begin, that’s a huge selling point. “When my oldest son was going through his major depressive episodes, we had a hard time finding the right person whom he would trust to talk to. Then we had to find the right medication. And when you have hormones and mental health issues, it’s not a great combination. You just have to keep trying.”
By age 10, Begin says her son was showing signs of obsessivecompulsive behaviour and depression. By the last year of high school, he would have panic attacks if she was late to the bus stop. He was admitted to the IWK Health Centre after threatening to harm himself. Prior to that, she says he had not responded well to a referral to a psychiatrist who specialized in attention deficit hyperactivity disorder.
“During the six months he saw that doctor, his medication was changed every two to three weeks. He lost 70 pounds. My son went from being a big tall guy to where you could see his ribs.” Johanna credits the team at the IWK for getting her teenage son back to health.
Fast forward many years to this spring. After a couple of setbacks (including flunking one year while trying to live without meds), Begin’s 25-year-old son will graduate with an engineering degree. And after being treated for severe anxiety, her daughter is studying to become a licensed practical nurse.
“Treating (bipolar disorder) with long-term medication can be effective,” Alda says. “However, no two individuals are alike, and choosing which treatments work best for individuals can take months and even years of trial and error. With the right genetic screening tools, we can more accurately predict which treatments are most likely to work for certain individuals.”
Research funding worth $975,000 from Genome Atlantic, the Dalhousie Medical Research Foundation, the Research Nova Scotia Trust, the Nova Scotia Health Authority, and Dalhousie University has been provided to fast-track the treatment of bipolar disorder.
“Genomics technologies hold great promise for a personalized medicine approach to diagnosing and treating mental illness, and the ground-breaking work done by Drs. Alda and Uher could significantly reduce the impact of bipolar disorder on the lives of patients and their families,” says Dr. Steve Armstrong, CEO of Genome Atlantic.
Alda says that while about 80 per cent of the odds of developing bipolar disorder are genetic, a variety of other factors — such as trauma and drug use — are also influential. And not everyone for whom the odds are high will develop a mental disorder. The three-year project will consider both heredity and environment to determine the most relevant factors.
“We hope to develop a clinical screening tool (a checklist including family history, reactions to drugs, and whether the person has short-term or long-term symptoms) in combination with taking a blood or saliva sample to measure genetic mutations in many genetic markers,” Alda says.
For the past three years, Johanna, her husband, and her two oldest children have been participating in another, ongoing study of families and brain chemistry at Dal. Once a year, they are interviewed at length and given some cognitive tests. They provide DNA samples and their brain activity is monitored by an MRI.
Johanna has grown to view her mental disorder as no different than having blue eyes or high blood pressure; she doesn’t resent the genetic link. Her immediate family has received good care.
At this time, she says they are not suffering from mental disorders, but living with them. It’s a key distinction she wishes more people were able to share. But she says too many are suffering because of limited governmentfunded access to diagnosis and psychiatric treatment. But that’s another story. Meanwhile, she’s optimistic this research may lead to faster, more effective treatment based on a better understanding of genetic material and other factors that make us who we are.