Sense of Scents

In Julie Walsh-Messinger’s narrow lab in St. Joseph Hall are tidy rows of what look like felt-tip color markers. The psychologist pops the top from one and raises it to the nose of her guest. The reaction is quick and predictable: the visitor rears back, her nose wrinkled, her eyes narrowed as she encounters the acrid smell of rotting fish. That fish stick is among the sharp probes in Walsh-Messinger’s toolkit; they’re called Sniffin’ Sticks, and with them, she can peer into the brain.

Or, to be more precise, Walsh-Messinger, an assistant professor in psychology at UD peers into the brain’s emotional machinery. The eyes may be the window to the soul, but the nose, it turns out, is the peep hole into gut feeling. While every sense makes its way to your gray matter, odor travels like a maglev train with no local stops. In an instant, an aroma arouses revulsion or a flood of warm fuzzies. You may, on reflection, realize the smell reminded you of your daughter as a newborn, but the warm fuzzies came by themselves, the reaction hair-trigger. You love it. You hate it. It makes you happy. It’s depressing. It’s scary. Before you think it through, you have the emotion.

Because of odor’s direct access to feelings, Walsh-Messinger is using her Sniffin’ Sticks to help solve the riddle of schizophrenia, a disease in which emotions fail to do the motivational work that life requires. Although we seldom realize it, every decision we make is impelled by emotion, Walsh-Messinger explains. It may be as simple as the pleasure of getting things done. Or it could be avoiding the discomfort of a missed deadline. Despite what Mr. Spock on Star Trek claimed, without a steady stream of emotional charges, he would have found no reason to stand on the bridge and warn Capt. Kirk of his errors in logic. He would have done nothing at all.

An emotional chain
In schizophrenia, something in the emotional chain is broken. By prying into the matter, Walsh-Messinger hopes to eventually develop treatments for schizophrenia and even strategies to prevent the devastating mental illness.
Most people are familiar with what psychologists call the “positive” symptoms of schizophrenia: hallucinations, delusions, disordered behavior — the stuff that gets you checked into the hospital. But fewer are aware of the “negative” symptoms: the lack of facial expression known as “flat affect,” impaired social functioning, social withdrawal, lack of motivation.

Walsh-Messinger realized early in her training from 2004 to 2006 that the deepest trouble in schizophrenia lies in these negative symptoms. She was working with young people at risk for the disease — some already exhibiting low-level symptoms — in the New York State Psychiatric Institute and Columbia University.

“I saw that the things that were most concerning to family members and most concerning to the people treating them were not the odd ideas or the perceptual abnormalities,” she says. “It was more their lack of motivation, their social isolation, their social fear.”

In fact, Walsh-Messinger’s mentor and collaborator, Dr. Dolores Malaspina, a professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, explains that the isolation and withdrawal symptoms tell practitioners who is most likely to get better. “If your symptoms of acting out really go out of control and get you hospitalized repeatedly, if you’ve [maintained] social and emotional capacity, that predicts a good outcome,” Malaspina says.

The negative symptoms wreak a special kind of havoc, Walsh-Messinger says: “That’s why people don’t work and aren’t able to find a way to construct meaning in their lives. These are also the symptoms that we don’t have good treatment for.” Every single drug for schizophrenia attacks the positive symptoms alone.

The Sniffin’ Sticks allow Walsh-Messinger to examine emotional reactions in people who don’t grin when they’re happy or frown when they’re sad. All they need to do is rate a smell on how pleasant it is, and then rate it again for unpleasantness — which is not as simple as it sounds, as we’ll explain later. The answers are emotional readouts that gradually reveal how the emotional experiences of people with schizophrenia differ from those without it.

Full immersion course change
Unlike her spartan lab space, Walsh-Messinger’s office has more stuff than storage space. Stacks of paper line the gray walls. A pile of research papers slouches and slides on the deep window sill. Black messenger bags containing psychological tests from her graduate assessment class lay on the floor. A pile of canvas bags full of books waiting to be unpacked is a reminder of her move into a new home last fall.

She’s clearly deep in her work, fascinated and fully engaged, with several projects going at once: a study mapping individual response to social situations that includes a smell component; research using smell to look for markers of aggression in schizophrenia; and even a project with a group of UD engineering and physical therapy faculty to determine how posture of those who use walkers influences falls — a study that doesn’t involve the sense of smell.

As a Boston College undergraduate, Walsh-Messinger says, she shed majors like last week’s pop songs, nearly a new major every semester. By the fall of her senior year, the only thing she was sure of was her interest in people.

“But I didn’t know what avenue I wanted to go down,” she says. “I was studying for the [Law School Admission Test] at the time, thinking I might want to go into law, and for the [Graduate Record Examinations], thinking I might want to go into psychology.”

Then she took a class called interpersonal relationships, which was heavy on psychoanalytic theory and ideas about how our earliest relationships with family, caregivers and teachers create lifelong patterns. “A couple of weeks in, I put down the LSAT book. I never picked it up again.”

But she didn’t see research in her future. “I thought I was going to go into clinical work,” she says.  “I was going to have a practice and treat people who are angry at their husbands or wives and mildly depressed.”

It wasn’t until 2004, when she took a job at Westborough State Hospital in Massachusetts while pursuing her master’s in counseling at Boston College, that her priorities changed. The adolescents at Westborough were diagnosed with a variety of disorders, including schizophrenia. She did a little of everything there, from helping patients prepare for dinner to sitting in on groups with a clinician. She even took part in activities at times.

“There was some dance party, a video game that had just come out, and I would do that. I would play with them, and they just laughed at this old person,” says Walsh-Messinger, who at 36 today could nearly pass for a well-dressed undergrad in her gray dress and black framed eyeglasses.

She also was able to read patients’ detailed case histories. “I began realizing how complicated these kids’ lives were. Some of them, by age 10, had far more complications than I will ever have in my life,” she says, such as having endured mental or physical abuse.

Walsh-Messinger underwent a full immersion in serious mental illness, a real look at the human side and the clinical details, and it jolted her curiosity and her compassion. “I wanted to understand and come up with some kind of treatment so that these kids didn’t need to be in a hospital — which was very naïve,” she says. But it was also
motivation.

The scent sense of a woman

While earning her doctoral degree at Long Island University – Brooklyn and working with Malaspina, Walsh-Messinger began to see the value of olfaction in the study of schizophrenia. Neurodegenerative diseases like schizophrenia are known to affect the sense of smell. A 2016 University of Florida study found that people with early stage Alzheimer’s disease couldn’t identify the smell of peanut butter. In a separate study, Mayo Clinic researchers tested the sense of smell of 1,400 healthy older adults, average age 79 years. Over the three-and-a-half years of the study, researchers found that sense of smell declined as memory problems increased. People with multiple sclerosis, Huntington’s and Parkinson’s disease all experience a loss in olfactory acuity.

Other research has shown that odor can have a profound impact in our everyday lives — often in ways we’re not even aware of. Neurobiologists at Stony Brook University illustrated the power of smell when they took sweat samples from first-time skydivers. Then they let people undergoing fMRI brain scans have a whiff of the fear sweat and watched while their amygdalas — the brain’s fear center — lit up. Sweat samples from skydivers running a treadmill produced no similar response. Other test participants presented with fear sweat were shown pictures with a range of facial expressions from neutral to angry. Normally, people focus on the angry face because of the threat anger represents.

But under the influence of eau de terror, the participants became acutely vigilant, giving each face equal attention. 
Critical to Walsh-Messinger’s research has been her decision to take an obvious fact into account: males and females are different. Medical and psychological research has a long history of ignoring this distinction, carrying on research on male participants and then generalizing the results to include females.

“Julie is ahead of her time in understanding the importance of sex differences in the symptoms of schizophrenia,” Malaspina says.

When Walsh-Messinger began her work, it was no secret that men and women with schizophrenia had different experiences. The average age of schizophrenia onset is younger in males — 18 to 25, compared to 25 to 35 in females.

There’s also a second peak in schizophrenia diagnosis for women around the time of menopause, suggesting that estrogen might have a protective effect. Further, men tend to have a worse course of disease, with more social and emotional deficits. Walsh-Messinger added to the insights on sex differences in schizophrenia with her recent paper in the journal Clinical Schizophrenia & Related Psychosis. That paper showed women with schizophrenia are more likely to exhibit what she calls “internalizing” symptoms, such as rumination and depression, while men are more likely to “externalize” with symptoms such as hostility and poor impulse control.

The difference between men and women even extends to the sense of smell. In a healthy population, women generally have a better sense of smell.

“I don’t see how you could study anything related to olfaction and not at least look at sex,” Walsh-Messinger says.

How sweet and sour it is

Another important innovation in her research has to do with her use of two scales to assess emotional response to scent. On one, research participants rate a smell for its pleasantness. On the other, participants rate the same odor for its unpleasantness.

That may seem redundant, but it actually gets at our emotional biology better than the traditional single scale, which has “strongly dislike” on one end and “strongly like” on the other. In between are all the subtle variations between love and hate. But what if that’s not actually how we really judge things? What if life is more like a SweeTart than the pure sugar rush of a Pixy Stix? Walsh-Messinger suspected the SweeTart was the better model.

“It wasn’t so much a clinical observation as it was just listening to friends talk,” Walsh-Messinger says. Even the sweetest moments often had a bit of sour to them, and vice versa. In fact, the brain is designed that way: We process pleasure on one circuit and displeasure on a completely distinct circuit. To ignore that subtly is to miss what people are saying about their experience.

Her research has uncovered subtle distinctions between how people with schizophrenia respond emotionally to a variety of odors. Participants completed two basic tasks. One was to identify a series of scents, the other was to rate each scent for its pleasantness and unpleasantness.

The study in 26 people with schizophrenia and 27 without showed that men with schizophrenia, in particular, had impaired olfaction, judging pleasant odors as more unpleasant than men without the disease. Women with schizophrenia rated pleasant odors the same way women without the disease rated them. Overall, test participants with schizophrenia were less able to identify odors accurately, especially when the odor was neutral or pleasant, a possible hallmark of neurodegenerative damage.

The more severe a person’s negative symptoms were — that is, the worse their social isolation and lack of motivation — the more topsy-turvy the emotional response to odors. People with more severe negative symptoms found pleasant odors more unpleasant. They also found unpleasant odors more pleasant.

Walsh-Messinger and her co-authors had anticipated people with more severe negative symptoms would show impairment, since problems with emotional processing are an important contributor to negative symptoms. 

The results further showed people with more prominent positive symptoms — delusions, hallucinations, disordered behavior — rated neutral odors as less pleasant and more unpleasant, which the researchers said fit the way positive symptoms work: They make people assign significance to meaningless stimuli, increasing their overall level of vigilance.

These results, being published in a forthcoming issue of the journal Psychiatry Research, are just a peek into the emotional world inside schizophrenia. From here Walsh-Messinger and her collaborators intend to look at olfaction as a potential predictor for aggression, and olfaction and the ability to navigate social cues.

“I think it’s amazing how much she’s accomplished,” Malaspina says, noting that Walsh-Messinger has been an assistant professor at UD for only three years. “I think her work will continue to be pioneering.”

It’s work that’s helping to open a window to a very confounding disease, but Walsh-Messinger remains focused on her larger goal.

“What my results don’t tell us is what’s causing this,” she says. “That’s the next big missing piece we need to figure out. That’s what I intend to spend, hopefully not the whole decade, but probably the whole decade, teasing apart. We can’t really figure out the treatment until we understand the cause.”