Photo: Eric Risberg (AP)

There is no singular cause of mental illness. Any number of things—our genes, environment, and even social mores—play a role in determining whether someone’s mental health will deteriorate to the point of being diagnosable as a disease. But researchers from Johns Hopkins have stumbled onto a possible trigger for manic episodes they didn’t expect to find: beef jerky.

Since 2001, researchers have been tracking the health of willing psychiatric care patients admitted at one of several hospitals in the Baltimore, Maryland area, a study that is still ongoing. In 2007, they started asking patients about their diets. One of the scientists behind the study, Robert Yolken, a neurovirologist at the Johns Hopkins University School of Medicine, initially set out to use this data to examine a possible connection between foodborne infections and mental illness.

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But as he and his team reviewed the anonymous data of more than 1,000 volunteers (a cohort that included the psychiatric care patients and a control group of people recruited from nearby health care centers and colleges with no diagnosis of mental illness), a strange pattern began popping up among people diagnosed with mania, a state of hyper excitement, arousal, and delusion frequently followed by periods of severe depression in people who have bipolar disorder. Compared to the control group, people with a manic episode reported eating more cured meats such as beef jerky. Overall, they found that people with a recent history of eating cured meat were three times more likely to be hospitalized for mania, even after adjusting for factors like age or socioeconomic status. The same pattern couldn’t be seen with any other type of food eaten.

“This is not what we were looking for,” Yolken told Gizmodo. “It came as something of an unexpected finding.”

Hoping to confirm that it was the jerky at fault, Yolken reached out to other researchers and started experimenting with rats. Because jerky and similar products are cured using nitrate salts, they theorized that nitrates might be the key driver of a mania effect.

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They first fed rats 14 grams of store-bought jerky every other day (the rat equivalent of one snack a day in humans) and compared them to a control group. The jerky-fed rats began showing symptoms of hyperactivity and poor sleep within two weeks, while the control group didn’t. Next, they fed specially made dried meat without nitrates to another group of rats, finding these rats didn’t develop any symptoms. And lastly, they gave rats a typical rat feed loaded with nitrates, and found the same pattern.

The study’s findings were published Wednesday in Molecular Psychiatry.

“It’s definitely intriguing, and probably better than many other studies that only rely on mice and rats,” Emeran Mayer, a gastroenterologist at the University of California Los Angeles who was not involved with the research, told Gizmodo.

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“The rat experiments are quite convincing... But in humans, it can be a lot more complicated,” said Mayer, who has studied and written about how the gut microbiome can influence the brain. “Dietary recalls and questionnaires are quite notoriously unreliable. So that’s probably a weak point of the study.”

As for how jerky could be triggering mania, Yolken suspects it involves the microbial environment, or microbiome, of the gut. In a healthy person, the gut and brain regularly “talk” to one another through hormonal and nerve signals to keep the body regulated, the so-called gut-brain axis. In recent years, researchers have started to find that our gut microbiota is integral to keeping those airwaves clear. But if the gut microbiome is imbalanced (through changes in diet or antibiotics, for instance), that might set off a chain of events that wreaks havoc on both the brain and gut, often through chronic inflammation. This inflammation then might make people more susceptible to developing mental illness, or worsening its symptoms.

And indeed, when Yolken’s team looked at the guts of nitrate-fed rats, they found clear changes in the gut microbiome, in the form of an increase of certain kinds of bacteria, compared to normal rats. Those particular bacteria have previously been associated with behavior and cognition changes in animals. There was also evidence of minute molecular changes in the brain associated with mania in these rats, though Yolken cautioned that the results can’t prove that the gut changes led to the brain changes. They also can’t prove that nitrates are responsible for any similar changes in people.

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Yolken himself points out that the study, especially the results in humans, isn’t definitive. No other study, as far as he knows, has linked nitrates to mental illness (though they have been linked to conditions like cancer when found in drinking water as a contaminant). And a lot more research, in both animals and people, is needed before any such link could be confirmed. Even if diet plays a role in mental illness risk, it’s only one of many factors that interact in complicated ways we don’t fully understand.

That’s self-evident, Mayer says, because nitrates, whether in hot dogs or beef jerky, are an ubiquitous part of the North American diet. Yet clearly, not everyone who loves hot dogs develops mania. So even if the link is real, it’s only one piece of the puzzle.

“Microbes don’t just cause anxiety, depression, or autism in people,” explained Mayer. “They only have an effect on people who have a genetic or environmental predisposition to illness, and it’s only one element among many.”

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Trying to fix the microbiome might not necessarily help treat all types of mental illness, either. Yolken and his team recently published a double-blind trial showing that mania patients who took probiotics—pills containing a mix of “good” bacteria thought to stabilize the microbiome— alongside standard treatment had a lower risk of being re-hospitalized for another episode within six months. But he has also published research that found probiotics had no effect on reducing the symptoms of people suffering from schizophrenia.

Still, Yolken hopes his study will spark more attention (and funding) toward studying the link between the gut, diet, and the mind.

“We don’t want to scare people about their diet, but this is definitely a promising area that needs to be further looked at and studied,” Yolken said.

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“I don’t suggest any interventions now,” he added.

[Molecular Psychiatry]