woman standing with cutouts of people

Maria A. Oquendo, MD, PhD, is probing the human mind and brain to prevent more lives from being lost to the tenth leading cause of death in the United States.

By Carole Bernstein
Photos by Peggy Peterson

Her speech is measured and considered, so her laugh takes the listener by surprise. It is loud, ringing, a little wild, and bursting with absolute enjoyment of life.

If you or someone you know is experiencing suicidal thoughts, contact a mental health professional. The National Suicide Prevention Lifeline is confidential and available 24 hours per day, 7 days per week to provide support, information, and local resources. Call 1-800-273-8255. The crisis text line is also available for those in crisis to connect with a trained crisis counselor via text message at 741-741.

PET and MRI imaging of a brain

Oquendo's key studies have drawn on PET and MRI imaging to map brain abnormalities in mood disorders and suicidal behavior. Depressed Bipolar patients have much lower levels of Serotonin Transporter (bottom panel) than healthy volunteers (middle panel). Hotter colors (red and yellow) indicate higher binding compared to cooler colors (blue and green).

The laughter is just part of what is remarkable about talking with Maria A. Oquendo, MD, PhD. With some people all it takes is a question or two and it's like flipping a switch; they're happy to go on and on about whatever's on their mind. But Oquendo has a quality of really listening. She wants to figure out exactly what you want to know. She appears to choose her words, and her answers, very carefully. Everything she says seems to express, at its core, the importance of clarity. The quality of her attention is slightly unnerving.

Most days, though Oquendo's personality exudes cheerfulness, that focused attention nevertheless is directed on exploring the darkest, most troubling recesses of the human mind: suicide.

It's the tenth leading cause of death in the United States. And it's on the rise: The U.S. Centers for Disease Control and Prevention (CDC) reported in 2016 that the nation's suicide rate hit a nearly 30-year high, and this June noted that rates continued rising in every state.

Oquendo, an internationally renowned expert on mood disorders with a special focus on suicidal behavior and global mental health, joined Penn last year as the department chair and Ruth Meltzer Professor of Psychiatry at the Perelman School of Medicine. Before that, she served as a professor of Psychiatry at Columbia University and research psychiatrist at the New York State Psychiatric Institute. In 2016-2017, she served as president of the American Psychiatric Association, the largest psychiatric association in the world with more than 37,000 physician members. She can boast (but generally doesn't boast) three decades' worth of awards and honors in her field. She began her career as a clinician, but since launching her research career 20 years ago has been continuously funded by the National Institute of Mental Health, has authored over 400 peer-reviewed publications, and became a member of the National Academy of Medicine.

No Easy Explanation

People who die by suicide are young and old, rich and poor. They are people's spouses, siblings, schoolmates, co-workers, babysitters, grandparents, neighbors. They have an obvious mental or physical illness or seem perfectly well. They appear to have lonely, isolated lives or fulfilling ones.

When they go, they may leave behind not just grief but guilt and questions. Those who knew them tend to speculate and try to explain why it happened. They may attribute it to a job loss, divorce, serious illness, or other hardship. I heard X's wife was unfaithful... Y's parents wouldn't pay to send her to college... It was probably because Z got fired...

But that's too simplistic, Oquendo says. The motivations for suicide are much more complex than people realize (and still not completely understood). “For many years, there's been a conceptualization of suicide as a catastrophic reaction to something that goes awry in a person's life,” she says. “But that doesn't really capture exactly what's happening.”

She gets impatient with news accounts that implicate an external cause, like drought causing a spate of suicide deaths among farmers, and will occasionally pen a letter in response. “No, that's not why the farmers are committing suicide,” she says. “I mean, okay, that doesn't help, but it's an interaction between some kind of psychiatric situation and the environmental stressor.”

Oquendo's key studies have drawn on PET and MRI imaging to map brain abnormalities in mood disorders and suicidal behavior. One of the important things we now understand about suicide, she says, is that there's a biological, genetic component. Scientists are finding physical abnormalities in the brains of people who have died by their own hand. These differences have also been detected in the brains of individuals who have tried to harm themselves.

She cautions, though, that while researchers can see differences across groups of people, the findings aren't yet at the stage where a brain scan on a single individual can yield a diagnosis. So unfortunately you can't just bring someone in for medical imaging to find out if they're at risk.

Biomarkers to predict suicidal behavior, especially highly lethal behavior, are urgently needed in order to improve prevention efforts, Oquendo and her co-authors stated in a landmark 2016 brain-imaging study published in JAMA Psychiatry. In the paper, the researchers determined that individuals who have greater elevations in their serotonin 1A receptor are more likely to engage in more medically damaging suicidal behavior in the next two years.

The receptor is “a marker of serotonin ‘tone,' if you will,” she explains, likening the concept to “how active the system is in the brain.” Significantly, the serotonin changes predicted how lethal the future suicidal behavior would be.

She notes, though, that just because someone has a genetic predisposition to suicide doesn't mean it will ever manifest itself. Some individuals with histories of suicidal behaviors in their families appear to be resilient to it. Oquendo also points out that treatments for conditions like depression or personality disorders can decrease suicide risk, even in individuals classified as high-risk. Therapeutic interventions matter.

Oquendo's research career is a trailblazing one, according to J. John Mann, MD, a professor of translational neuroscience in Psychiatry and Radiology at Columbia, and her mentor there. He says she is the kind of scientist who stays true to the data no matter how unpopular the findings might be. He recounts how in 2011 she published a study in the American Journal of Psychiatry which challenged the current thinking about lithium having certain anti-suicidal effects. “Instead of massaging the data — even though it flew in the face of all of the previous extremely promising but not as well-designed studies, and a lot of big names had lined up their opinions and reputations behind this idea — she went ahead and published.” (How did the field react? “Stony silence,” Mann says.)

Mann finds Oquendo's research accomplishments all the more remarkable because her path was not the traditional one. She had spent much of her career as a clinician before deciding to pursue research with his group. Mann says he had told her bluntly that her odds of success were low because she lacked sufficient background in statistics, brain biology, and imaging. “But I think that just made her more determined,” he says. She tenaciously got herself up to speed, started running studies, and eventually began getting NIH grants, he says. “I don't know anybody [else] who had done that. She is amazing and inspiring.”

Maria A. Oquendo, MD, PhD sitting in a chair
Oquendo's professional interest is in a serious subject, but her joyful, ringing laughter is warm and welcoming to colleagues and trainees.

Defining Suicidal Behavior — Down to the Details

Oquendo calls the early 2000s “a really interesting time in suicide research” because of one particular high-profile controversy: Concerns arose among parents that prescribing antidepressants to children and teenagers might increase suicidal behavior. She notes, however, that there actually were no suicide deaths in any of the relevant studies. “Zero,” she says. “But there was a lot of consternation; a lot of families were worried.” But what exactly constituted suicidal behavior?

The FDA didn't have clear definitions. The agency commissioned Oquendo, then a researcher at Columbia University Medical Center, and colleagues Madelyn Gould, PhD, MPH, Barbara Stanley, PhD, and Kelly Posner, PhD, to investigate. The team created standards for defining suicidal behavior. Soon thereafter, the 2004 requirement for black box warnings — the highest level of FDA alert — was placed on all antidepressant medication labeling. The system was also endorsed by the CDC, and is now used worldwide. Oquendo and her colleagues even made it into the popular press, recognized as “Influentials” in the health arena by New York magazine.

In that classification system, a key refinement and extension of older such systems, the team identified sub-categories of suicidal behavior that had never been well described. One was “interrupted suicide attempt”: For example, a person enters the room and knocks a gun out of the suicidal person's hand, saving their life. Another was “aborted suicide attempt,” in which someone might pick up a deadly implement but then change their mind about using it. And “preparatory acts” refers to someone perhaps purchasing a deadly substance and writing a suicide note but going no further.

These subtleties are important to identify, says Oquendo, because they can be used to predict a person's future level of risk for taking their life. Columbia's John Mann agrees, and adds that, because people who engage in suicidal behavior are being found to have different patterns of suicidal ideation, different biology, and varying responses to stress, the one-treatment-fits-all approach seems increasingly inadequate. “One may need to think about different risk groups and have strategy designed more specifically for them,” he says.

Oquendo points out that psychiatrists and other therapists haven't traditionally asked their patients for a lot of details around suicidal behavior: “Clinicians often thought about suicidal behavior as a binary variable: yes or no, did they attempt to kill themselves or not.” But she says the better we can describe the activities a patient has engaged in, the number of times they did them, and so forth, the better we can determine their degree of risk.

The Oquendo-Gould-Stanley-Posner classification system is not only useful for psychiatrists. The team tested a group of international experts and a group of pediatricians to see how they evaluated a set of case records. Once trained in the classifications, says Oquendo, the pediatricians were just as good as the international experts in distinguishing actual suicide attempts from non-attempts. As a result, a variety of providers can be involved in prevention efforts.

Oquendo says she's excited about a current research project to identify two new subtypes of suicidal behavior with different biological underpinnings. The subtypes are “planful” behavior in which the person methodically sketches out exactly what they're going to do, versus a person who appears to take their life on an impulse. The studies involve both brain scans and measurements of stress responsivity. Study participants are exposed to different stressors and their cortisol levels are measured. Oquendo's team has begun analyzing data; they plan to publish findings in the coming months.

Cultural (In)Sensitivity

two cutouts of people with their spines highlighted

Global Mental Health: Doing More with Less

Imagine you lived in a country that only had 13 psychiatrists, total, to treat every mental condition. That's the situation of Mozambique, a nation of 28 million people. And many other countries are in similar straits.

An expert in global mental health in addition to her U.S. research and administrative activities at Penn, Oquendo and her former Columbia colleague, psychiatrist Milton Wainberg, are trying to figure out the most efficient, cost-effective ways to serve people's mental health needs when resources are stretched impossibly thin. This type of research is known as implementation science. Wainberg points out that in addition to helping people in sub-Saharan Africa, findings from the project could eventually be applied to other low- and middle-income countries and regions, including in the U.S.

The team is working with a new type of provider known as a psychiatric technician, and is also training community health workers, with an eye toward ensuring the implementation techniques are sustainable among the local populations.

The effort in Mozambique began in 2014, and last year the team received funding not only to continue the work in that country but to begin capacity-building in Botswana, Malawi, South Africa, and Zambia. Collaborating with local health ministries, the researchers are testing the best strategies to implement comprehensive mental health — encompassing all psychiatric disorders, substance abuse, and epilepsy—and to provide care that includes both psychotherapies and medication.

“Even in [the U.S.] we don't have enough psychiatrists — you're never going to have enough psychiatrists,” Oquendo says. “So how can we develop a system of care so that people can be attended to given the paucity of human resources?” The joint Penn-Columbia effort may yield practical solutions that could help millions of people.

If you or someone you know is experiencing suicidal thoughts, contact a mental health professional. The National Suicide Prevention Lifeline is confidential and available 24 hours per day, 7 days per week to provide support, information, and local resources. Call 1-800-273-8255. The crisis text line is also available for those in crisis to connect with a trained crisis counselor via text message at 741-741.

While suicide is often viewed as the most extreme outcome of severe depression, it's important to understand that this isn't always the case, Oquendo says. She points out that suicide is seen in a variety of psychiatric conditions: Ten percent of people with alcoholism kill themselves, and 10 percent of people with schizophrenia. Eating disorders and anxiety disorders “also seem to predispose,” she says.

In fact, Oquendo believes suicide should be classified as “its own thing” as opposed to a symptom of other mental illnesses. She was the first to propose that suicide be given its own diagnostic category, stating it would help psychiatrists more effectively track high-risk patients. She succeeded in getting it added to the DSM-5 in 2013, but only to the appendix: “What that tells you is there's a little bit of resistance to this concept.”

She thinks the resistance may stem from a Western-centric view prevalent in the field. In Western culture, she says, one almost never sees suicide as a stand-alone phenomenon, separate from another psychiatric illness. But in India, China, and other cultures, many people who die by suicide are reported not to have an additional psychiatric condition. While acknowledging that differences in reporting may be a factor, she asserts that the way Western medicine classifies disease “doesn't necessarily have sensitivity to other cultural expressions of things.” In addition to her other research, Oquendo studies mental health in countries outside the U.S. and Europe. With her former colleague Milton Wainberg, MD, a professor of clinical psychiatry and global mental health at Columbia, Oquendo is working on projects in sub-Saharan African countries including Mozambique, where there are a mere 13 psychiatrists serving a nation of 28 million people. The joint Penn-Columbia team is trying to figure out the most efficient, cost-effective ways to serve people's mental health needs when resources are stretched so impossibly thin.

Oquendo's interest in how culture and psychiatry intersect has a personal element. Half Puerto Rican and half Spanish (and the only Latina president in the American Psychiatric Association's 173-year history), she grew up in a traditional household in which girls and women were in supportive roles. She says being Latina is important to her and her identity: For example, she works hard to keep her fluent Spanish from slipping away.

The flip side of this background is that Oquendo's rise through the profession has included encounters with prejudice. “Unfortunately, I can give you a lot of examples,” she quips. One incident that sticks in her mind happened a few years ago at a conference at another Ivy League university. Dressed professionally for the event, she went to the registration desk but was told her name wasn't on the list. She told the staffer, “That's really strange because I'm giving a talk in about 20 minutes.” It turned out the woman was checking the support staff roster instead of faculty. “She was so embarrassed, as you can imagine,” Oquendo recalls. “I actually felt bad for her.”

Wainberg notes that Oquendo has worked to be inclusive of diversity “of all kinds of minorities, without compromising rigor or quality.” Carolyn Rodriguez, MD, PhD, an assistant professor of Psychiatry and Behavioral Sciences at Stanford who had Oquendo as her residency director, calls her a champion of diversity and inclusiveness. Rodriguez notes that Oquendo started an annual “Celebration of Diversity” dinner at her home and took actions to increase the recruitment of underrepresented minorities. She says that in one year she increased the diversity in the psychiatry residency class significantly, from 5 percent to 25 percent.

Wainberg observes that beyond having cultural competency, a psychiatrist needs to have cultural proficiency, meaning that simply providing unbiased care isn't enough. A therapist should understand and appreciate the positive role a patient's culture may play in their well-being. “With so much diversity in the United States, we see diverse patients… [We need] that sort of more nuanced understanding of how culture plays a role,” Rodriquez agrees.

Oquendo's cultural background has also contributed to her value as a mentor for past trainees, including Rodriquez, who is Puerto Rican. “It's an amazing thing as an up-and-coming researcher to see people who look like you in positions of leadership and doing well scientifically,” she says. Rodriguez also fondly remembers Oquendo's accessibility as a mentor. “Maria often left her door open [to visitors], which is a wonderful thing for junior faculty and residents… and hearing her jovial laugh down the hall always put everyone at ease.”

Share This Page: