In Dr. Julie Walsh-Messinger’s narrow lab are tidy rows of what look like felt-tip color markers. Except instead of colors, each holds a smell — from rotting fish to pineapple. Because of odor’s direct access to feelings, Walsh-Messinger is using these Sniffin’ Sticks to better understand schizophrenia — and hopefully eventually develop ways to treat and prevent it.

Although we seldom realize it, every decision we make is impelled by emotion, Walsh-Messinger explains. In schizophrenia, something in the emotional chain is broken.  

While earning her doctoral degree at Long Island University and working with Dr. Dolores Malaspina, a professor of psychiatry at the Icahn School of Medicine at Mount Sinai, 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 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.  

Walsh-Messinger’s research has uncovered subtle distinctions between how people with schizophrenia respond emotionally to a variety of odors. To make this discovery, participants first identified scents from the Sniffin’ Sticks and then rated each one on how pleasant — and unpleasant — it was.

Why rate scents on two scales? Even the sweetest moments often have a bit of sour to them, and vice versa, Walsh-Messinger explained. 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.

The study 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. 

People with more severe “negative” symptoms of schizophrenia — lack of facial expression, impaired social functioning, lack of motivation — found pleasant odors more unpleasant. They also found unpleasant odors more pleasant. Walsh-Messinger and her co-authors had anticipated that 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 that people with more prominent “positive” symptoms — delusions, hallucinations, disordered behavior — rated neutral odors as more unpleasant and less pleasant, 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, published in Psychiatry Research, are opening 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. We can’t really figure out the treatment until we understand the cause.”

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In addition to her research on olfaction and schizophrenia, Walsh-Messinger has studied sex differences in schizophrenia. Her recent paper in the journal Clinical Schizophrenia & Related Psychoses showed that women with schizophrenia are more likely to exhibit “internalizing” symptoms, such as rumination and depression, while men are more likely to “externalize” with symptoms such as hostility and poor impulse control.