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A Common Food Brought on This Woman’s Psychosis

“She did not conform to any known psychiatric illness.”

Wanda Guerreiro, now 54, doesn’t remember being admitted to Centro Hospitalar de Lisboa Ocidental, the general hospital in Lisbon, Portugal, in 2011. Her family brought her in because she began to say strange things, then behave in strange ways, until she was unrecognizable as the person they knew before.

Bernardo Barahona-Corrêa, the head of the acute inpatient psychiatric unit, initially thought Guerreiro might have a personality disorder. She switched quickly between extreme agitation and catatonia—a state of being completely immobile. In her states of anxiety, she would tear her clothes apart and run naked through the wards. She tried to eat non-edible objects, like plants and rocks. When they took her to the hospital garden, she tried to eat bird feces. She was aggressive with the doctors. Barahona-Corrêa says she couldn’t sustain a normal conversation. She’d change subjects mid-sentence, or say one thing, then say the opposite.


While Guerreiro underwent a battery of exams, Barahona-Corrêa talked with her baffled relatives and tried to piece together her medical history. Guerreiro’s family met with Barahona-Corrêa several times. But the one clue Barahona-Corrêa needed to figure out what had gone wrong in Guerreiro's mind remained hidden.

“Although we interviewed them again and again, and went through all the medical history, it never turned up,” he tells me, thinking back.

The weeks dragged on. Barahona-Corrêa says they were at a loss for how to treat her, let alone diagnose her. Personality disorder no longer felt right. Neither did any of the other major psychiatric diseases he had diagnosed many times before. He says that when a person has a psychiatric disease, like schizophrenia, it manifests as a cluster of typical symptoms. For example, schizophrenics have delusional ideas, believe things that aren’t true, and hear voices. This wasn’t the case with Guerreiro. There was nothing typical about her. Her symptoms jumped all over the psychiatric map, morphing as each day went on.

Her thoughts were disorganized, but she didn’t have any delusions. She wasn’t hearing voices, and she didn’t have any feelings of euphoria. She didn’t seem to be clinically depressed. Sometimes she would spend one or two days crying, but then her mood would shift completely.

“She did not conform to any known psychiatric illness,” Barahona-Corrêa says. “Another thing that struck me as being strange was her age. This was someone who had been living her life normally up to the moment when she was admitted to the hospital. It was really hard to figure how it could be that she had suddenly developed, at a relatively late age, a severe mental illness that wasn’t present before.”


Guerreiro wasn’t responding to any of the interventions that they tried: antidepressants, anxiolytics, antipsychotics or even electroconvulsive therapy. She was also physically unwell. After one month in the hospital, she had lost 10 percent of her weight, and her blood work showed that, despite supplementation, she had a variety of vitamin deficiencies. Then she started to have intestinal complaints: unexplained diarrhea, cramps, then constipation for a couple of days followed by a return of the diarrhea.

“At a given point we started actively investigating her general medical problems,” Barahona-Corrêa says. They looked closer at her digestive system, and gave her an abdominal CT.

Suddenly, Barahona-Corrêa found something conclusively wrong with her. Her scan showed thickening of the gut lining and other indications of celiac disease. They confirmed with her family the clue they had been missing: She had had gluten sensitivity since she was a little girl. Her family hadn’t thought it was relevant. And why would they?

Was it possible, Barahona-Corrêa thought, that her celiac disease was related to her psychiatric symptoms?

Celiac disease is an autoimmune disorder that affects around one in 100 people. If you have it, eating gluten–a protein found in wheat, rye and barley–triggers an immune response in the body.

In most cases, this attack happens in the small intestine, which is what Barahona-Corrêa saw in Guerreiro’s scans. But in the last 20 years, research has been showing that celiac disease and gluten sensitivity can also affect the brain. Cases of psychiatric presentations of celiac disease are rare—just a few pepper the literature—but neurological symptoms are becoming increasingly recognized. And they can sometimes appear without any of the classic gastrointestinal signs of celiac disease.


Isobel Salisbury is a 69-year-old woman who lives in Sheffield, England. Her mother, grandmother, and uncle all had a severe form of ataxia, a neurological condition that can lead to an inability to walk, eat with a fork, button your shirts, swallow food, and more. It was even called the “Salisbury complaint,” because it was so well known to run in her family. When Salisbury’s doctor heard about it, he sent her to Marios Hadjivassiliou, a neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, who has been treating a special kind of ataxia since he first described it in the early 1990s.

When Hadjivassiliou began his neurology career, he heard of people with celiac disease developing unexplained neurological problems, but they were isolated reports. After caring for a patient with profound neurological symptoms who also had celiac disease, he started screening all of his patients whose neurological issues didn’t have an obvious cause. He looked for specific antibodies to gluten, called antigliadin antibodies, in a person's blood, which tell him that a person’s immune system was reacting in some way to gluten proteins. This antibody can be present with or without celiac disease, though many also have celiac.

Hadjivassiliou says that it’s still not clear exactly how gluten can cause neurological problems, just that in these patients with gluten antibodies, a gluten-free diet makes their problems resolve or improve. Typically, when the body mounts an immune response against gluten, you develop celiac disease. But there are different types of enzymes that process gluten, and they’re all expressed in different parts of the body: some in the gut, some in the skin, and some in the brain. Each enzyme interacts with and can bind with parts of gluten proteins. It's thought that a person with gluten sensitivity is responding with an immune attack on both the gluten proteins themselves and also on the enzymes that break it down. Depending on which enzyme the body reacts to may explain why some people develop neurological problems while others present with the bowel symptoms or a skin rash.


Now, in Sheffield, Hadjivassiliou has close to 1,000 patients with neurological problems related to celiac disease and gluten sensitivity. The symptoms can appear as ataxia, a loss of balance and coordination, and neuropathy, or a sensory loss in the feet and hands because of damage to nerve endings, or other neurological deficits.

When Hadjivassiliou ordered a lumbar puncture and some blood tests for Salisbury, he found that she had antigliadin antibodies in her blood. Genetic testing for inherited ataxias were all negative. He diagnosed her with gluten ataxia and put her on a gluten-free diet. They speculate that that’s the form of ataxia her family members had too, though gluten ataxia does not usually run in families.

Hadjivassiliou’s work has shown there can be a connection between a gluten response and the function of the brain. But loss of coordination is one thing; what about full-blown psychosis?

“The psychiatric side of things hasn’t been really extensively explored,” Hadjivassiliou tells me. “It’s plausible, but it’s not been something that has been reported extensively. Unless you do big population studies, as we’ve done with the neurological cohort, it’s difficult to say how commonly celiac disease and gluten sensitivity could be implicated in psychiatric problems.”

“I had never seen a case of celiac disease presenting primarily as a behavioral change, as a psychiatric syndrome,” Barahona-Corrêa says. “It was completely new to me. I had several of my younger collaborators helping me out. Everyone was searching the literature, and there were several brainstorming sessions about this patient.”


They read Hadjivassiliou’s work, and others that showed that people with celiac and gluten issues had a higher co-occurrence of psychiatric issues. Deanna Kelly, a psychiatric pharmacist and researcher at the Maryland Psychiatric Research Center and the University of Maryland Baltimore, tells me that in the general population celiac disease is about 1 percent. It is higher among people with schizophrenia, at about 3 percent. And over the past 20 years, she’s also found that about a third of people who have schizophrenia also have those same antibodies to gliadan, even if they don’t have classic celiac disease.

She’s looked at immune profiles, and found that people who have high gluten antibodies and schizophrenia have more activated immune systems. She’s also found markers of brain inflammation, by looking at levels of neurochemicals that are high in diseases of inflammation, like MS. These are all preliminary correlations, but she thinks that this subgroup of people with schizophrenia or psychosis—people who have antibodies to gluten, and inflammation in the body and brain—might find some relief from a gluten-free diet.

Kelly thinks that on a very basic level what's happening is this: Gluten is getting into the body and triggering an immune response that has an effect on the brain. She doesn’t know if gluten causes psychiatric symptoms in these patients, or exacerbates pre-existing conditions. Her first step, she says, is to see if going gluten-free can help at all. She has finished a pilot study, not yet published, in which 16 people who met her requirements reported that their negative symptoms improved as a result of cutting gluten from their diets. In August of 2017, she received the first grant funded by NIH for a large clinical trial involving gluten and schizophrenia.


The clinical trial will take place over the next four years. Once they find participants who have high levels of the gluten antibodies, she’ll admit them to an inpatient unit of a state hospital in Maryland for five weeks. They’ll go on a completely gluten-free diet, and each person will get protein shakes every day; half of the study participants will have gluten flour in their shakes and half will not, in a randomized way. It will be a double-blind study, so Kelly won’t know who’s receiving gluten or a shake with rice flour instead.

She hopes that understanding the connection between gluten, the immune response, and psychosis could provide an effective way for this subset of people to reduce their symptoms. It’s not the majority of patients with psychiatric issues, but psychiatrists need to know. “Most psychiatrists would never think to test for these antibodies,” she says. “People that have high antibodies to gliadin are out there and may benefit from a gluten-free diet, but without testing few are ever going to know.”

Hadjivassiliou says that even for more established neurological effects of gluten, more awareness is needed. If gluten is causing a person's ataxia or neuropathy, it will continue to get worse if the person doesn’t stop eating it. Neurological centers need to incorporate the proper screening to rule out gluten sensitivity, he says. He’s been publishing studies in this area for more than 20 years, he says, and there are still people who just don’t believe it. “I don’t know what that means,” he tells me. “It’s not a religion; you just have to look at the literature and read it and then decide for yourself.”


When Barahona-Corrêa and his team read about the possible link between gluten and psychiatric cases, it was hard for them to accept. “When we finally suspected this, it was was difficult for us,” he says. “We are psychiatrists, we are not specialists in internal medicine or gastroenterology. It was really hard to convince our colleagues: ‘Well that’s what we think she has, so please look into this.’ They didn’t think it was the case.”

But none of the other medications or treatments were working. The only way to test their theory, as off the wall as it was, was to put Guerreiro on a gluten-free diet.

Guerreiro dramatically improved, and quickly. All her lab results normalized, her stomach complaints went away, and the erratic and disorganized patient Barahona-Corrêa and his team had been struggling with all but vanished. After two months, she was on minimal medication–something for sleep, and not much more. She was released from the hospital. Her file was memorialized in the BMJ's Case Reports.

“She was very relieved when we discharged her,” Barahona-Corrêa says. “She appeared to be shaken, in a way. She didn’t remember much that had happened. We described to her things that she had done. She really didn’t recognize herself. She was very shaken by how it could come to this." Guerreiro felt fragile. How could something so simple, a dietary choice, have had such widespread consequences?


“I don’t remember a thing, you know,” Guerreiro tells me over Skype. She pauses, trying to find the right words. “I asked my son: ‘Why? Why did I do that?’ It’s not possible that I threw glasses and plates at a window. If it was not my son and my sister that told me, I don’t know if I would have believed it.”

Guerreiro says that it seemed too incredible that gluten could be the issue. When she was released from Barahona-Corrêa and his team’s care in 2012, she still wasn’t convinced, and wasn’t consistent with her diet. Some of her strange behavior returned. She began to beg for money and cigarettes in the street, and stopped showering or caring about personal hygiene.

Again, her memory started to become unreliable, and her son and sister had to tell her about the odd things she was doing. When she went to a doctor’s appointment in 2016, they told her that her celiac disease markers were very high, and they were concerned about a relapse. It was the wake-up call she needed.

Image courtesy of Wanda Guerreiro.

“I finally realized that gluten is like a poison to me,” she says. “I heard the doctors say I am intolerant to gluten, but I know now it’s more. When I finally realized that gluten was my poison, I stopped eating it. And now, for about two years, I haven’t had any gluten. I am feeling lighter, more stable and happy. Like myself again.”

Not everyone is so lucky. In 2014, a 37-year-old woman arrived at Massachusetts General Hopsital, with psychiatric symptoms she could not explain. Alessio Fasano, a gastroenterologist and celiac researcher, says he remembers vividly the first day she came in, because she opened their discussion by saying, “I want my life back.”


“She said she believed she was a bright person,” Fasano tells me. “She was a PhD student, on her way to get her degree, living alone, independent. Then she got hit with this unbelievable change in behavior. It was like a split personality. She said she was doing stuff she typically would not do. Like shoplifting, getting very belligerent, and to the point where she suspected her family was poisoning her.”

A few months after her psychotic symptoms began, her apartment was burglarized. Her parents had a key, and so she thought they were involved and made a threat against them, leading to her being taken to an inpatient state psychiatric facility. She was diagnosed with psychotic disorder and possible paranoid schizophrenia.

Under further medical examination, the woman was found to have nutritional deficiencies, trouble absorbing vitamins, and thyroid disease. She was treated for her thyroid, and diagnosed with celiac disease through a biopsy. But she thought her doctors were being “deceitful” about her diagnosis, according to her case report in the New England Journal of Medicine, and refused to go on a gluten-free diet.

Her psychotic symptoms and paranoia continued. “She continued to ‘find clues’ of conspiracy against her,” the report says. “She lost her job, became homeless, and attempted suicide; her family took out a restraining order against her. Eventually, she was re-hospitalized at a psychiatric facility, where she was placed on a gluten-free diet.”


After three months, her delusions had gone away. She was discharged; that’s when she sought out Fasano for an explanation for how gluten could change her so much. “She was scared, and she decided to come to me,” Fasano says. “She said that she knew people didn’t believe her. They thought it was an excuse to justify her behavior. She described herself like Dr. Jekyll and Mr. Hyde. Two different personalities in the same person.”

She told Fasano she wanted to be exposed to gluten in a safe setting, and have the results documented, so that she could have indisputable proof that there was a cause-and-effect relationship between the gluten and her psychotic behavior.

Fasano tells me it wasn’t that easy. He had to convene ethical groups and other teams of experts at the hospital, so they could discuss what the proper treatment should be. After a long deliberation, they decided they would test her with gluten and see what happened.

But by then, though, it was too late. The patient had been accidentally exposed to gluten again, become delusional and was re-hospitalized. Fasano says that her case seems more complicated than Guerreiro's. She had more conflating medical issues, and it was hard to tease out if she had an already-existing psychiatric problem that was exacerbated by the gluten, or how big of a role the gluten played. And unlike Barahona-Corrêa’s team with Guerreiro, Fasano wasn’t able to examine how the diet affected her symptoms under his care.

“I’m not being arrogant when I say I think Wanda was lucky," Barahona-Corrêa tells me. "We had a moment with her when we were really concerned that if her family decided to take her to an institution, she would not have gotten better, and maybe even have died. It could have had a fatal outcome.”

Fasano’s patient's 2016 case report (written after she was treated at Massachusetts General) says that her levels of antibodies had previously been normal when she was lucid and off gluten. But they were elevated the last time they encountered her, her doctors wrote. She was no longer following her gluten-free diet because “of a delusion that the diagnosis of celiac disease is incorrect,” the report wrote.

“Where is she right now? I don’t know for sure,” Fasano says. “But she hasn’t contacted us anymore. Once she was [recontaminated], she lost control of everything. I wish that we could have done more for this young lady.”

“We must be clear in our minds that cases such as this are rare,” Barahona-Corrêa tells me. “I’m not going to see this again in my career. But the main message is: We must have a more expansive approach when we have patients with intriguing presentations.”

After her ordeal, Guerreiro relied heavily on the support of her family. She eventually got a job at a coffee shop, and recently started working as a secretary at a real estate office. Barahona-Corrêa says he's grateful that his team was made up of young doctors who were willing to consider an explanation that they had never heard of.

“What cases such as this teach us is that we must have high-degree suspicion, and low threshold for starting to investigate medical and neurological causes or explanations for symptoms that are not completely typical,” he says. “These days we have access to lots of complementary diagnostic things: MRI; scans. It’s unforgivable if a patient gets admitted to the psych ward in a general hospital, has a medical or neurological problem, and the problem is undetected. It’s really inexcusable.”

I ask Guerreiro if she feels lucky. She says she doesn’t know how to explain exactly how she feels, because she doesn’t remember the bad stuff. It’s been told to her like a story, one that still feels borderline unbelievable. What she does know is that for her, inexplicably, gluten almost caused her to lose her grasp on life.

“I know that gluten almost took me,” she says. “Now, I am completely back to normal. It’s amazing. My doctor said that I almost died. I almost died and I was born again. Born again for a new life.”

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