Study shows link between genetics and response to electroconvulsive therapy

October 28, 2022 —

Electroconvulsive therapy (ECT) is a treatment reserved for the most severe cases of depression, bipolar disorder, and schizophrenia. Positive results are not guaranteed.

Could genetic evidence in the form of a patient’s “polygenic risk score” help predict whether electroconvulsive therapy will be effective for that patient?

That’s the focus of a recently published study American Journal of Psychiatryjointly led by Dr. Kaarina Kowalec, Assistant Professor of Pharmacy in the Rady Faculty of Health Sciences at UM.

A polygenic risk score is derived from testing a patient’s DNA. It reflects the patient’s “polygenic liability” for certain diseases, based on the presence of genetic biomarkers.

“There are differences in our genetics that can increase the risk of conditions like depression and bipolar disorder,” says Kowalec. “Scientists are beginning to demonstrate that genetic biomarkers can also tell us whether someone is more likely to respond to a particular treatment. We may be able to use this information to improve patient outcomes.”

The goal of improving patient outcomes was the focus of Kowalec’s research. When her mother was diagnosed with multiple sclerosis (MS), she wanted to understand why some people with neurological or psychiatric conditions tend to have poor outcomes.

“I began to realize how much was unknown about these disorders,” she says. “For the past five years, I have researched serious illnesses such as schizophrenia and MS that have not responded to treatment.”

In movies like One flew over the cuckoo’s nestelectroconvulsive therapy was negatively portrayed as a treatment for psychiatric disorders. But it can be extremely helpful for people who haven’t responded to other forms of treatment, Kowalec says.

The electrical current given to the patient after the anesthesia causes a brief seizure, which can lead to changes in brain chemicals. Patients are usually given the treatment 8 to 10 times before they start seeing improvement.

The rate of remission after treatment is quite low, between 30 and 50 percent. Although it is a safe procedure, it can have negative side effects such as memory loss.

“Patients may not want to risk the side effects if their genetics indicate they are unresponsive,” says Kowalec. “With the polygenic risk score, patients could make more informed decisions with fewer risks.”

Kowalec, who has a PhD in genomics and epidemiology, completed a postdoctoral fellowship in Sweden before joining UM in 2019. She co-led the recently published study with Dr. Robert Sigstrom and Dr. Mikael Landén from the Swedish University of Gothenburg.

Researchers analyzed more than 2,300 patients in Sweden who were undergoing electroconvulsive therapy for a major depressive episode and agreed to have their DNA tested using a blood sample.

The results showed that a higher polygenic risk score for major depression was significantly associated with a lower chance of improvement after therapy. “This means that a person who is genetically more prone to major depression is less likely to respond well to ECT,” says Kowalec.

On the other hand, genetic predisposition to bipolar disorder was associated with greater improvement after ECT. The study found no association between polygenic liability for schizophrenia and the effectiveness of treating a major depressive episode.

Researchers hope to expand the project to study patient responses to ECT worldwide. They also want to explore the relationship between polygenic risk scores and other forms of psychiatric treatment.

“Based on certain genetic markers, healthcare professionals could classify patients into those who are more likely and less likely to respond to a particular treatment,” says Kowalec. “This could help patients get the treatment that works best for them much earlier, without trying a range of ineffective therapies.”

Allyn Lyons