Dysregulation of Microbiota in Patients With First-Episode Psychosis Is Associated With Symptom Severity and Treatment Response.

BACKGROUND: The gut microbiome has been implicated in the pathogenesis of mental disorders where the gut-brain axis acts as a bidirectional communication network. METHODS: Herein, we investigated the compositional and functional differences of gut microbiome between patients with first-episode psychosis (FEP) (n = 26) and healthy control participants (n = 22) using whole-genome shotgun sequencing. In addition, we assessed the oral microbiome in patients with FEP (n = 13) and listed their taxonomic diversity. RESULTS: Our findings suggest that there is a dysbiosis of gut microbiota in patients with FEP. Relative abundance of Bifidobacterium adolescentis, Prevotella copri, and Turicibacter sanguinis was markedly increased (linear discriminant analysis scores [log10] > 1, and Mann-Whitney U test; false discovery rate-adjusted p values < .05) in the FEP group compared with the healthy control participants. Pathway analysis indicated that several metabolic pathways, particularly deoxyribonucleotide biosynthesis, branched-chain amino acid biosynthesis, tricarboxylic acid cycle, and fatty acid elongation and biosynthesis, were dysregulated in the FEP group compared with the healthy control group. In addition, this preliminary study was able to identify specific gut microbes (at baseline) that were predictive of weight gain in the FEP group at a 1-year follow-up. Bacteroides dorei, Bifidobacterium adolescentis, Turicibacter sanguinis, Roseburia spp., and Ruminococcus lactaris were positively associated (eXtreme gradient boosting, XGBoost regression model, Shapley additive explanations, R2 = 0.82) with weight gain. CONCLUSIONS: Our findings may suggest the involvement of gut microbiota in the pathogenesis of psychosis. The benefit of modulation of the gut microbiome in the treatment of psychotic disorders should be explored further.

Immunomodulatory effects of antipsychotic treatment on gene expression in first-episode psychosis.

Previous studies suggest immunological alterations in patients with first-episode psychosis (FEP). Some studies show that antipsychotic compounds may cause immunomodulatory effects. To evaluate the immunological changes and the possible immunomodulatory effects in FEP, we recruited patients with FEP (n = 67) and matched controls (n = 38), aged 18-40 years, from the catchment area of the Helsinki University Hospital and the City of Helsinki, Finland. Fasting peripheral blood samples were collected between 8 and 10 a.m. in 10 ml PAXgene tubes. We applied the NanoString nCounter in-solution hybridization technology to determine gene expression levels of 147 candidate genes reflecting activation of the immune system. Cases had higher gene expression levels of BDKRB1 and SPP1/osteopontin compared with controls. Of the individual medications used as monotherapy, risperidone was associated with a statistically significant upregulation of 11 immune system genes, including cytokines and cytokine receptors (SPP1, IL1R1, IL1R2), pattern recognition molecules (TLR1, TLR2 and TLR6, dectin-1/CLEC7A), molecules involved in apoptosis (FAS), and some other molecules with functions in immune activation (BDKRB1, IGF1R, CR1). In conclusion, risperidone possessed strong immunomodulatory properties affecting mainly innate immune response in FEP patients, whereas the observed effects of quetiapine and olanzapine were only marginal. Our results further emphasize the importance of understanding the immunomodulatory mechanisms of antipsychotic treatment, especially in terms of specific compounds, doses and duration of medication in patients with severe mental illness. Future studies should evaluate the response pre- and post-treatment, and the possible role of this inflammatory activation for the progression of psychiatric and metabolic symptoms.