Interest renewed in targeting gluten in schizophrenia

ORLANDO – Going gluten free shows a benefit for a subset of schizophrenia patients, and it offers a new array of potential intervention – suggesting that knowing what some patients consume or interrupting newly identified mechanisms could make real differences in symptom severity, an expert said at the annual congress of the Schizophrenia International Research Society.

Deanna L. Kelly, PharmD, director of the Treatment Research Program at the University of Maryland, Baltimore, said that if she’d been told 10 years ago that she’d be studying links between diet and schizophrenia, “I would have probably not believed you.”

Interest in the link between wheat, which contains gluten, and schizophrenia is not brand new. Research published in the 1960s found that, as wheat consumption fell in Scandinavia during World War II, so did hospital admissions for schizophrenia. In the United States, schizophrenia admissions rose as wheat consumption rose. But interest in the topic died off in the 1980s, when links between a gluten-free diet and schizophrenia symptoms were found to be weak or nonexistent.

Dr. Kelly said that’s because that research looked at all comers without a finely tuned schizophrenia population.

More recent work has found that the culprit in gluten linked to schizophrenia symptoms appears to be gliadin, a protein that helps bread rise during baking and is hard to digest. Researchers have found that antibodies to other gluten proteins – such as anti–tissue transglutaminase antibodies, used to diagnose celiac disease – are not elevated in schizophrenia patients, compared with healthy controls (Schizophr Res. 2018 May;195:585-6). But native gliadin antibodies (AGA IgG) are significantly elevated – this is seen in about 30% of patients, compared with about 10% in controls, Dr. Kelly said.

Elevated AGA IgG is also correlated to higher levels of peripheral inflammation and higher levels of peripheral kynurenine, a metabolite of tryptophan linked to schizophrenia.

In a feasibility study with 16 patients published this year, researchers randomized patients with elevated AGA IgG to a gluten-free diet – they were fed with certified gluten-free shakes – or a diet that wasn’t gluten free over 5 weeks. Patients stayed at a hospital to ensure adherence to the diet and for close monitoring. They found that those who were gluten free showed significant improvement in negative symptoms, measured by the Scale for the Assessment of Negative Symptoms, compared with those who continued eating gluten. These symptoms included the inability to experience pleasure, inability to speak, lack of initiative, and inability to express emotion (J Psychiatry Neurosci. 2019 Mar 27;44[3]:1-9).

“Removing gliadin may improve negative symptoms in schizophrenia,” Dr. Kelly said.

Those on the gluten-free diet also showed improvement in gastrointestinal symptoms and improvement in certain cognitive traits, such as attention and verbal learning.

Her research team is now conducting on a larger trial comparing the two diets, this time with the gluten-containing diet involving a higher amount of gluten, which researchers think better reflects real-life diets.

Researchers are still not sure how gliadin intake affects schizophrenia symptoms, but it could involve problems with the blood brain barrier, the permeability of the gut, or the effects on the microbiome, she said. But the importance of gliadin and gluten to this group of schizophrenia patients raises the possibility of treatment with ongoing dietary changes, anti-inflammatory treatments, blocking absorption of gluten, improving how it’s digested or by blocking gliadin antibodies.

“We’re trying to learn about disease states themselves, but each person should find their best lives,” Dr. Kelly said. “Everyone deserves optimized and personalized treatment.”

Dr. Kelly reported financial relationships with Lundbeck and HLS Therapeutics.

ORLANDO – Going gluten free shows a benefit for a subset of schizophrenia patients, and it offers a new array of potential intervention – suggesting that knowing what some patients consume or interrupting newly identified mechanisms could make real differences in symptom severity, an expert said at the annual congress of the Schizophrenia International Research Society.

Deanna L. Kelly, PharmD, director of the Treatment Research Program at the University of Maryland, Baltimore, said that if she’d been told 10 years ago that she’d be studying links between diet and schizophrenia, “I would have probably not believed you.”

Interest in the link between wheat, which contains gluten, and schizophrenia is not brand new. Research published in the 1960s found that, as wheat consumption fell in Scandinavia during World War II, so did hospital admissions for schizophrenia. In the United States, schizophrenia admissions rose as wheat consumption rose. But interest in the topic died off in the 1980s, when links between a gluten-free diet and schizophrenia symptoms were found to be weak or nonexistent.

Dr. Kelly said that’s because that research looked at all comers without a finely tuned schizophrenia population.

More recent work has found that the culprit in gluten linked to schizophrenia symptoms appears to be gliadin, a protein that helps bread rise during baking and is hard to digest. Researchers have found that antibodies to other gluten proteins – such as anti–tissue transglutaminase antibodies, used to diagnose celiac disease – are not elevated in schizophrenia patients, compared with healthy controls (Schizophr Res. 2018 May;195:585-6). But native gliadin antibodies (AGA IgG) are significantly elevated – this is seen in about 30% of patients, compared with about 10% in controls, Dr. Kelly said.

Elevated AGA IgG is also correlated to higher levels of peripheral inflammation and higher levels of peripheral kynurenine, a metabolite of tryptophan linked to schizophrenia.

In a feasibility study with 16 patients published this year, researchers randomized patients with elevated AGA IgG to a gluten-free diet – they were fed with certified gluten-free shakes – or a diet that wasn’t gluten free over 5 weeks. Patients stayed at a hospital to ensure adherence to the diet and for close monitoring. They found that those who were gluten free showed significant improvement in negative symptoms, measured by the Scale for the Assessment of Negative Symptoms, compared with those who continued eating gluten. These symptoms included the inability to experience pleasure, inability to speak, lack of initiative, and inability to express emotion (J Psychiatry Neurosci. 2019 Mar 27;44[3]:1-9).

“Removing gliadin may improve negative symptoms in schizophrenia,” Dr. Kelly said.

Those on the gluten-free diet also showed improvement in gastrointestinal symptoms and improvement in certain cognitive traits, such as attention and verbal learning.

Her research team is now conducting on a larger trial comparing the two diets, this time with the gluten-containing diet involving a higher amount of gluten, which researchers think better reflects real-life diets.

Researchers are still not sure how gliadin intake affects schizophrenia symptoms, but it could involve problems with the blood brain barrier, the permeability of the gut, or the effects on the microbiome, she said. But the importance of gliadin and gluten to this group of schizophrenia patients raises the possibility of treatment with ongoing dietary changes, anti-inflammatory treatments, blocking absorption of gluten, improving how it’s digested or by blocking gliadin antibodies.

“We’re trying to learn about disease states themselves, but each person should find their best lives,” Dr. Kelly said. “Everyone deserves optimized and personalized treatment.”

Dr. Kelly reported financial relationships with Lundbeck and HLS Therapeutics.

ORLANDO – Going gluten free shows a benefit for a subset of schizophrenia patients, and it offers a new array of potential intervention – suggesting that knowing what some patients consume or interrupting newly identified mechanisms could make real differences in symptom severity, an expert said at the annual congress of the Schizophrenia International Research Society.

Deanna L. Kelly, PharmD, director of the Treatment Research Program at the University of Maryland, Baltimore, said that if she’d been told 10 years ago that she’d be studying links between diet and schizophrenia, “I would have probably not believed you.”

Interest in the link between wheat, which contains gluten, and schizophrenia is not brand new. Research published in the 1960s found that, as wheat consumption fell in Scandinavia during World War II, so did hospital admissions for schizophrenia. In the United States, schizophrenia admissions rose as wheat consumption rose. But interest in the topic died off in the 1980s, when links between a gluten-free diet and schizophrenia symptoms were found to be weak or nonexistent.

Dr. Kelly said that’s because that research looked at all comers without a finely tuned schizophrenia population.

More recent work has found that the culprit in gluten linked to schizophrenia symptoms appears to be gliadin, a protein that helps bread rise during baking and is hard to digest. Researchers have found that antibodies to other gluten proteins – such as anti–tissue transglutaminase antibodies, used to diagnose celiac disease – are not elevated in schizophrenia patients, compared with healthy controls (Schizophr Res. 2018 May;195:585-6). But native gliadin antibodies (AGA IgG) are significantly elevated – this is seen in about 30% of patients, compared with about 10% in controls, Dr. Kelly said.

Elevated AGA IgG is also correlated to higher levels of peripheral inflammation and higher levels of peripheral kynurenine, a metabolite of tryptophan linked to schizophrenia.

In a feasibility study with 16 patients published this year, researchers randomized patients with elevated AGA IgG to a gluten-free diet – they were fed with certified gluten-free shakes – or a diet that wasn’t gluten free over 5 weeks. Patients stayed at a hospital to ensure adherence to the diet and for close monitoring. They found that those who were gluten free showed significant improvement in negative symptoms, measured by the Scale for the Assessment of Negative Symptoms, compared with those who continued eating gluten. These symptoms included the inability to experience pleasure, inability to speak, lack of initiative, and inability to express emotion (J Psychiatry Neurosci. 2019 Mar 27;44[3]:1-9).

“Removing gliadin may improve negative symptoms in schizophrenia,” Dr. Kelly said.

Those on the gluten-free diet also showed improvement in gastrointestinal symptoms and improvement in certain cognitive traits, such as attention and verbal learning.

Her research team is now conducting on a larger trial comparing the two diets, this time with the gluten-containing diet involving a higher amount of gluten, which researchers think better reflects real-life diets.

Researchers are still not sure how gliadin intake affects schizophrenia symptoms, but it could involve problems with the blood brain barrier, the permeability of the gut, or the effects on the microbiome, she said. But the importance of gliadin and gluten to this group of schizophrenia patients raises the possibility of treatment with ongoing dietary changes, anti-inflammatory treatments, blocking absorption of gluten, improving how it’s digested or by blocking gliadin antibodies.

“We’re trying to learn about disease states themselves, but each person should find their best lives,” Dr. Kelly said. “Everyone deserves optimized and personalized treatment.”

Dr. Kelly reported financial relationships with Lundbeck and HLS Therapeutics.