The genomics of severe major depressive disorder (MDD) and response to electroconvulsive therapy (ECT)

Award: $39,990

Depression is the leading cause of disability worldwide. It can lead to suicide which is the second leading cause of death in 15-29 year olds. We need to identify patients with the most severe forms of depression, characterize them well, and include these patients in genomic studies. We know that such an approach will lead to new discoveries faster than studying patients with more mild forms of these disorders. We think that we have a way to do this. We want to identify people that have been treated with electroconvulsive therapy (ECT) for depression and include them in genetic studies. We think that findings from this study can lead to predictive algorithms. We want to learn whether we can, very early on in treatment, or identify people who will likely respond well to ECT vs people who will likely respond poorly or have bad side effects from ECT.

Need/Problem: Why some people get severe depression and why their depression responds to ECT is currently not well understood.

Grant Summary: This grant is for a new project to efficiently identify, characterize and get DNA from patients with severe depressive disorders. We want to connect all of this information to their response to ECT.

Goals and Projected Outcomes: The goal of our study is to better understand the genetic makeup of people with depressive disorders. We will do this by focusing on those that are severely affected. We will identify such people by finding patients with a history of receiving ECT. We will use available information to characterize these patients and their response to ECT. We aim to recruit 1000 patients locally. We will use this information to understand how these patients are different from patients that do not get ECT. We will also compare patients that respond to ECT to those that did not.

Takahiro Soda, M.D., Ph.D.

Grant Details: Depression is the leading cause of disability worldwide. It can lead to suicide which is the second leading cause of death in 15-29 year olds. The Psychiatric Genomic Consortium (PGC) recently identified 44 genetic variations called single nucleotide polymorphisms (SNPs)that are more common in people with major depressive disorder (MDD, P=8×10-10). The PGC also identified 30 SNPs that are more common in people with bipolar disorder (BPD).

Unfortunately, many of the subject samples came from poorly characterized forms of these mood disorders. This limits our ability to connect these genetic findings with response to treatments, or predicting the course of a person’s depression. We need to identify patients with the most severe forms of depression, characterize them well, and include these patients in genomic studies. We know that such an approach will lead to new discoveries faster than studying patients with more mild forms of these disorders.

What has limited such an approach is that charactering patients is not easy. If we solely rely on researchers to do the characterization, it would take hours for each patient, and we need to recruit thousands of patients to achieve our goals. We need an efficient way to rapidly identify, consent, quickly (but accurately!) characterize, collect DNA, and genotype people with depression. This gives us a better chance of finding genetic differences that will affect how we treat each patient with depression.

We think that we have a way to do this. We want to identify people that have been treated with electroconvulsive therapy (ECT) for depression and include them in genetic studies. ECT treatment is currently reserved for those with the most severe forms of depression. Second, the patients that get ECT are seen by a psychiatrist that does ECT that decides whether that patient should be offered ECT. During that visit the psychiatrist records information that we want to collect. Third, every time the patient gets ECT treatment their mood is assessed. This means that their response to ECT is tracked. People that get ECT are well characterized and all this information is available in their medical records.

This project, the genomics of severe major depressive disorder (MDD) and response to electroconvulsive therapy (ECT) aims to rapidly identify, consent, quickly characterize, collect DNA and genotype people with depression using available medical records at UNC.

We will ask people getting ECT at UNC whether they would consent to provide a blood sample and let us collect information from their medical records. We have created a data collection tool that lets us get the information we want in less than 15 minutes from the medical records. This means that the patient just has to give us blood, and permission. There is no research interview or special test they need to take.

We think that findings from this study can lead to predictive algorithms. We want to learn whether we can, very early on in treatment, or identify people who will likely respond well to ECT vs people who will likely respond poorly or have bad side effects from ECT.

2019-04-16T15:40:26-04:00