Natasha Kulviwat is no ordinary high schooler. She spent the first six months of last year in a lab at Columbia University, studying brain tissue from people who had committed suicide.
Her research investigated if any biomarkers — physical and measurable substances in the brain — might help explain and, perhaps someday, prevent suicide.
Ultimately, her work won her the Gordon E. Moore Award for Positive Outcomes for Future Generations and $50,000 for college expenses at the Regeneron International Science and Engineering Fair, an international competition for pre-college students organized by the Society for Science.
Identifying biomarkers of suicide in the human brain
Kulviwat found differences in the brains of 10 people who died by suicide compared to the control group: 10 people who died of other causes.
The brains of those who died by suicide, which were donated for study by their next of kin, contained higher numbers of inflammatory cytokines.
Cytokines create inflammation as a normal part of your immune system’s response to pathogens. But your body can also release them when there is no threat — during chronic stress, for example — and that can cause excessive inflammation.
Too much inflammation in the body over time can have many negative effects — it’s implicated in conditions like heart disease, cancer, and autoimmune disease. In this case, Kulviwat’s research suggests that inflammation affected a specific protein in the brain known as claudin-5.
Claudin-5 is usually found in cells that make up the blood-brain barrier (BBB) — playing an important role in regulating what substances can pass from the blood into brain cells.
But Kulviwat found elevated levels of claudin-5 in other parts of the brain — in the neurons and microvessels — of those who died by suicide, indicating there was a breakdown of the BBB.
This means that foreign agents can enter the functional brain areas, which could be neurotoxic. The results suggest elevated levels of claudin-5 in the brain might serve as a biomarker of suicide risk.
Can biomarkers be a new way to measure suicide risk?
According to the Centers for Disease Control and Prevention, suicide risk is usually evaluated by looking at things like a history of depression or other mental illness, life circumstances such as adverse childhood events or job loss, and other subjective psychological factors — like impulsivity or a sense of hopelessness.
Though treatments for suicidal behavior exist, including psychotherapy and medications, suicide rates have mostly increased over the last 20 years. In 2021, more than 48,000 people died from suicide. And there were an estimated 1. 7 million attempts.
A review of the research, published in 2021, found some potential biomarkers — including chemicals involved in the body’s stress response or that interact with serotonin — but none of the studies looked at claudin-5.
Kulviwat and other researchers hope that identifying a physiological process involved in suicide — that is, looking at suicide as not only a psychological issue — might help more accurately predict who is at risk than current methods and aid in developing more targeted pharmaceutical treatments for prevention.
Interestingly, in her research, Kulviwat found that some psychiatric medications used to help suicidal patients with issues like depression or anxiety, like Lexapro and benzodiazepines, don’t strongly interact with claudin-5 — but some anti-inflammatory medications do. What’s more, in some cases, psychiatric medications can even increase suicide risk.
Kulviwat said, of course, that doesn’t mean we should just give out anti-inflammatories to people who may be contemplating suicide. More research is needed, but Kulviwat said she’s “trying to see if it might be worth identifying an alternative.”
Dr. David Feifel is a neurobiologist and professor emeritus of psychiatry at the University of California San Diego. He is also the medical director of the Kadima Neuropsychiatry Institute — where he utilizes newer treatments like ketamine and transcranial magnetic stimulation for mental health conditions. He said Kulviwat’s results were interesting, but noted they should be treated as a correlation, not causation.
Feifel said the brain abnormalities Kulviwat found could be the result of a more fundamental abnormality, and claudin-5 may have no direct link to suicide.
“Before having any impact on the field, her findings have to be replicated in larger samples,” Feifel said.
Kulviwat also noted that her study was “very preliminary,” and that the sample size wasn’t that high. But she plans to continue the research.
“I’m going to be co-author on a National Institute of Health grant with my lab. We’re going to try to drill into this research more since the pilot study gave promising results, and then we’ll see where that takes us.”
Why study suicide?
Currently finishing up her junior year in high school, Kulviwat began researching suicide her freshman year — looking at possible psychological contributors — like impulsivity and lowered ability to cope with change.
But for this project “I wanted venture into the neurological perspective because not many studies do that,” Kulviwat told Insider.
Part of her interest in suicide research comes from volunteering with the American Foundation for Suicide Prevention and attending Out of the Darkness Walks — events that help raise awareness and provide support to people who have lost loved ones to suicide.
Hearing different perspectives and questioning why suicide research isn’t progressing as much as other fields — like cancer or infectious diseases — inspired her research, she said.
She said that juggling her academic obligations, personal life and lab work was one of the most difficult parts of this project. She often had to choose her research over time with friends — working in the lab until late in the night and over the holidays. Kulviwat said, laughing, that she even had to sometimes miss her high school classes to work in the lab.
Kulviwat already has research in mind for her next project. She plans to look at how medications like anti-inflammatories interact with claudin-5 in an animal model. The research could lead to the development of alternative treatment options for BBB failures and those at risk of suicide.
She said that the money she won was a big help in paying for college. But overall, it didn’t change much. I’m just like any other high school student. I haven’t taken my standardized tests yet. I’m still trying to pass my classes, trying to keep my GPA up.”
Kulviwat hopes to attend medical school in the future and become a pediatrician or pediatric psychiatrist.
“It’s imperative that we build a solid foundation for our children and that they are safe. I don’t think this is something that should be overlooked.