AJP Report Recognized for Suicide-Prevention Potential

When Zachary Kaminsky, Ph.D., submitted his article “Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors” to the American Journal of Psychiatry in January 2014, he wasn’t anticipating any scientific stardom.

The paper, which showed that people who had suicidal thoughts or died by suicide had higher than normal levels of chemical modifications near a gene called SKA2, was certainly intriguing. Previous work had identified some genetic changes that were associated with suicide risk, but this was the first time that epigenetics had been demonstrated to play a role.

The epigenetic aspect presented some interesting promise, as unlike hardwired genetic changes to DNA, epigenetic modifications—adding or removing chemical groups to the DNA—can be altered during a person’s lifetime, suggesting suicidal tendencies might be dampened in some people. And the study was able to detect SKA2 chemical changes in blood samples, raising a glimmer of hope that a simple diagnostic blood test for suicide risk could be developed.

These aspects had helped generate a fair amount of scientific and media attention for his AJP article, including in these pages (Psychiatric News, August 15, 2014).

Still, this past December Kaminsky, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, was a bit surprised when a colleague tipped him off that he would soon receive some major recognition; a couple of days later, his article was selected as one of the “Top 100 Stories of 2014” by Discover magazine (coming in at #45).

Though honored with the attention, Kaminsky understands that his work represents only the tip of the iceberg in terms of the potential of SKA2 and other epigenetic changes as biomarkers that can be used to predict suicidal behaviors, and he has not been resting on any laurels as he progresses his discovery forward. However, he did take a few moments to talk with Psychiatric News about the publicity of his study and his plans for the coming year.

What were your reactions when you first heard that your article was selected for this honor by Discover magazine?

I would say I had mixed feelings about the news. Certainly I was very excited when I first found out; it’s nice to know that other people are seeing the promise of what this finding represents, which is the promise that epigenetics has in terms of developing biomarkers and personalized medicine. But while it’s nice to be recognized and gain a lot of press for having a good discovery, I also have reserved feelings as I know we are not there yet. I’ve told people I know that I won’t really be happy until we translate this research and save lives. That’s the dream of someone who works in a lab as opposed to a clinic.

I think there’s a lot of compelling things about this story. The gene we uncovered—SKA2, which is related to our stress response—just made a lot of sense in terms of its function, and we had a lot of replication studies that made the results more valid and believable. There was also the epigenetic angle, which added a new twist. But you know, about a year before we came out with our paper, a group from Indiana University developed a blood-based biomarker based on gene expression, and that study received a lot of buzz too; so it may just be that people want solutions for serious problems like suicide and are tuned in to new discoveries.

Of course. Media attention is a fine line to walk. We’ve gotten contact from people who asked if they could be signed up for testing, and we’ve politely informed them no test is available yet. The word “genetics” also has strong implications, and the public often assumes when genetics are mentioned that risk is inherited, though our study didn’t address this possibility at all. As a consequence, we’ve had a lot of people call us worried about their children because of their family history, so clearly we need to do a better job of addressing these fears preemptively. On the other hand, to make a product clinically available, it helps to partner with companies or people that have the resources to help make that dream into a reality. So in that regard, media hype does generate interest from such entities, and that helps us move this ball forward with more power than I can push by myself.

One of the first things we did was get on the phone with a bunch of researchers who already have genomic datasets and see if we can use our models to predict suicide phenotypes in other people’s data. We’re continuing to work with Army STARRS [Army Study to Assess Risk and Resilience in Servicemembers] to compare our biomarkers in pre- and post-deployment situations, and we also recently got in touch with a Dutch researcher who has access to datasets with other military populations. Obviously I don’t want to risk any future publications, but I can say that we are encouraged by what we are seeing, and that I am cautiously optimistic for the year ahead.

That’s going to be a challenge to answer; to be honest, this finding has kept me so busy over the past few months with travel, setting up a new grant, and other activities that I have to admit I’m falling behind on my reading. That being said, there is a lot of important work being done by colleagues in psychiatric epigenetics. Alicia Smith and Elisabeth Binder published a paper recently providing a thorough analysis of peripheral tissue types that may have biomarker relevance to brain. Also, Eric Nestler’s group is performing very interesting work into in vivo epigenetic modifications in the nucleus accumbens to prove the causal effects of various epigenetic modifications to brain-related outcomes. I have seen abstracts for some interesting articles related to transgenerational PTSD, suggesting epigenetics may help to link epidemiological observations with psychiatric phenotypes. These and many more papers demonstrate the rapid rate the field is advancing and moving science in what I consider the right direction. I hope to take a closer look at more of them once I can catch my breath. ■

An abstract of “Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors” can be accessed here. The Indiana University study mentioned by Kaminsky is “Discovery and Validation of Blood Biomarkers for Suicidality,” and is available here.