Liam Davenport

April 06, 2016

FLORENCE, Italy — Patients with first-episode schizophrenia have alterations in gut microbiota that may be linked to inflammatory changes, say an international team of researchers, who found that antipsychotic therapy may also affect the intestinal environment.

Jaana Suvisaari, MD, from the National Institute for Health and Welfare, Finland, and colleagues demonstrated that the gut microbiota could be grouped into two clusters, one of which was more common in patients with first-episode psychosis.

Dr Suvisaari showed that patients with first-episode psychosis who have these characteristic changes in microbiota were significantly more likely to have been treated with the antipsychotic olanzapine (multiple brands).

The data were presented here at the Schizophrenia International Research Society (SIRS) 2016 Biennial Meeting.

Reducing Metabolic Side Effects

Although Dr Suvisaari noted that a great deal more analysis in larger samples is required before definitive conclusions can be drawn, she told Medscape Medical News that it was "interesting" that olanzapine appeared to be driving the clustering, especially given that the mean duration of therapy was just 20 days.

Dr Jaana Suvisaari

"Was it affecting the gut microbiota?" she asked. "This is something that really needs to be studied, because it might then help us understand why olanzapine has these other adverse metabolic effects, which may be partly due to changing gut microbiota."

She added that, following further study, "if we really see that there are differences, then it would be logical to try to influence that difference, [perhaps with] probiotics."

For the study, the team recruited 28 patients, aged 18 to 40 years, with first-episode psychosis. The patients, along with 16 healthy control participants, were recruited from the catchment area of Helsinki University Hospital using the Population Register Centre. All participants completed psychiatric rating scales and questionnaires on lifestyle, diet, and symptoms, and blood and fecal samples were collected.

DNA was later extracted from the fecal samples and analyzed to create paired end libraries 100 nucleotides in length that were sequenced, initially to remove low-quality and human sequences. Normalizing the read counts, the team clustered the identified sequences to a species level and, failing that, a genus level, and then compared the results between case participants and control persons.

The team identified two distinct clusters of fecal microbiota in patients and control persons, with 22 participants in each group. It is notable that the two clusters were not characterized by the overrepresentation of individual classes of microbial strains.

Further analysis determined that patients with first-episode psychosis were more likely to belong to cluster 1 than cluster 2, at 17 patients vs 11 patients (P = .06). Patients with first-episode schizophrenia were significantly more likely to belong to cluster 1 than 2, at 13 vs nine patients (P = .033).

There was no association between clusters and participant age, sex, or body mass index, and there were no associations between cluster membership and cholesterol levels or high-sensitivity C- reactive protein test results.

The team did find, however, that membership of cluster 1 was significantly associated with higher levels of tumor necrosis factor–alpha in comparison with cluster 2 (P = .048). Moreover, patients with first-episode psychosis in cluster 1 were significantly more likely than those in cluster 2 to use olanzapine, at 52.4% vs 11.1% (P = .041).

The findings suggest a possible link with recent research suggesting, for example, that a high-fat diet may be associated with an increased risk for anxiety and depression. A position statement calls for dietary changes to improve mental health.

"This was one of the reasons to study," said Dr Suvisaari. "Another reason is that the microbiota has a lot of metabolic roles in humans, producing some metabolites that otherwise we don't see.

"So another role might be in influencing the metabolic comorbidities that [psychosis] patients develop.... The most interesting possibility, of course, is that it actually would be affecting their symptoms."

Dr Suvisaari reports no relevant financial relationships.

Schizophrenia International Research Society (SIRS) 2016 Biennial Meeting: Poster T11, presented April 5, 2016.

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