The Biology of Suicide

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CHRISTOPHER FRUEH: Of course, we're concerned about people committing suicide. It's a common form of death in America.

MAN: If we're going to cure this epidemic, we have to ask new questions, like why are some of us more prone to suicide? Is it in our brain structures? Is it in our DNA? And if so, how can we use this information to save lives?

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CHRIS FOWLER: The patients that we see, we want to know about their early childhood, their development, how they did in school, every medication they've ever been on, every treatment they've been in. We want to know how depressed and how anxious are they?

We rely on clinical judgment, on all sorts of channels of communication, including non-verbal, paralinguistic communications. But those are even limited, because I am limited by, one, my ability to read them, and, two, by their ability to communicate.

So in the case of someone who's feeling suicidal, they might not know the causes that cause them to feel so out of sorts.

MAN: Due to the limitations of traditional psychiatry, we asked ourselves, what if we are able to include our psychiatric data, along with biological data? Would that help us diagnose and then treat suicidal patients? It's these kinds of questions that lead to the birth of the MIND-MB Project.

CHRISTOPHER FRUEH: One of the things that's exciting to me is it's no longer purely psychology or purely psychiatry that's working on this. This is a vast, multi-disciplinary group.

MAN: The MIND-MB Project is made up of clinical psychologists, neuroscientists, and geneticists, all working together to crack the code of psychiatric illness. This level of collaboration is really unprecedented in our field.

Neuroimaging, which is studying the structure and the functioning of the brain, is definitely helping us better understand suicidal ideation, which is essentially the act of thinking about and planning one's suicide.

RAMIRO SALAS: Most of the brain is wiring, right? So we have the gray matter, which are where the cells are living. And then the cells send these axons in big bundles. So there's these big groups of axons that are like big cables that go from one place the brain to another.

CHRIS FOWLER: If an individual does not have the adequate number of fibers, enough information communicating between two areas of the brain that they don't learn well from disappointment. And those people are more likely to be persistently suicidal.

RAMIRO SALAS: There is here these very, very small two white dots right in the center of the brain. It's called a habenula, and it's my favorite area. I even love the word "habenula" now.

When you're disappointed or punished, the habenula activates. And when the habenula activates, your dopamine centers, meaning your reward and your pleasure, goes down.

For example, suicidal ideation—people with more suicidal ideation have this particular bundle of fibers tends to be bigger if you have more suicidal ideation.

CHRIS FOWLER: This finding that the number of fibers connecting the habenula to other parts of the brain actually has a role to play in suicidality, we would never have guessed that. We might be able to predict that it would have some impact on substance use. But suicidality was completely a surprise to me.

RAMIRO SALAS: Now, if we have all this imaging data, can we separate patients according to genetic characteristics, right?

CHRISTOPHER FRUEH: Well, I knew from the time I got here, the day one, I started looking for a molecular geneticist. I think there's no question that there's a genetic component to suicide. If we can track the kind of outcomes and the kind of patients, if we can draw their blood and bring all of that together, that would be wonderful.

DAVID NIELSEN: So now, we're breaking the white blood cells open. And we're going to spin out the protein. And the solution will contain the DNA, and then we'll precipitate DNA out. There it is. This is a purified DNA. The DNA is your instructions for how your body and your brain is made.

Genetics have been shown to have a large influence on our behaviors. If we identify specific genes that are involved in that, we know what those genes code for, and we'll understand the pathways that are involved in the patient's development of suicidal ideation. We can say this gene is not being expressed enough. Let's target that pathway using different pharmacotherapies.

MAN: So when we bring together data from psychiatric evaluations, neuroimaging, and genetics, we hope to target new treatments, such as new pharmacological agents, new neurostimulation approaches, in order to improve our outcomes.

CHRIS FOWLER: We will be better able to synthesize a very personalized approach to medicine and take out at least some of the guesswork early in the treatment, because when patients experience benefit early in treatment, it's like a snowball. It builds. And they feel like they have some agency and effectiveness in their own lives. And that takes on its own power.

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