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Studies of the composition of the gut microbiome have consistently shown that psychiatric disorders such as schizophrenia are associated with gut dysbiosis. However, research focusing on adolescents with early-onset psychosis remains limited. This study aimed to characterize the microbial communities and their potential metabolic functions in these populations. We identified that genera Desulfovibrionaceae_Incertae_Sedis, Paraprevotella, and several genera from the Oscillospiraceae family were significantly more abundant in patients with schizophrenia compared to non-psychotic individuals, while Dorea showed decreased levels in schizophrenia patients. Furthermore, patients with early-onset psychosis demonstrated a significant reduction in Staphylococcus abundance. Additionally, we observed an increase in Prevotellaceae Leyella and Prevotellaceae Incertae Sedis in patients receiving atypical antipsychotic treatment, along with a rise in the genus Weissella among those treated with sertraline. Conversely, patients on valproate treatment exhibited decreased levels of Desulfovibrionaceae Incertae Sedis, while showing increased levels of Kandleria and Howardella. Functional prediction analysis using PICRUSt2 revealed significant differences in the expression of key enzymes associated with fatty acid metabolism. Gene orthology analysis identified 10 differentially expressed genes in the early-onset psychosis and schizophrenia groups. Our findings underscore the importance of considering dietary factors, pharmacological treatments, and microbial composition in understanding the gut–brain axis in psychiatric disorders.

The relationship between the gut-brain-microbiome axis has gained great importance in the study of psychiatric disorders, as it may represent a new target for their treatment. To date, the available literature suggests that the microbiota may influence the pathophysiology of several diseases, including psychosis. The aim of this review is to summarize the clinical and preclinical studies that have evaluated the differences in microbiota as well as the metabolic consequences related to psychosis. Current data suggest that the genera Lactobacillus and Megasphaera are increased in schizophrenia (SZ), as well as alterations in the glutamate-glutamine-GABA cycle, serum levels of tryptophan, kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). There are still very few studies on early-onset psychosis, thus more studies are needed to be able to propose targeted therapies for a point when the disease has just started or has not yet progressed.

Abstract The combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p

Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional differences were observed in Hannum and Horvath clocks when comparing chronological age and years of CLZ treatment. We identified 44,716 differentially methylated sites, of which 87.7% were hypomethylated in CLZ-treated patients, and enriched in the longevity pathway genes. Moreover, by protein–protein interaction, AMPK and insulin signaling pathways were found enriched. CLZ could promote a lower Δage in individuals with long-term treatment and modify the DNA methylome of the longevity-regulating pathways genes.

Abstract Background Evidence suggests that liability for suicide behavior is heritable; additionally, suicide has been partly related to other psychiatric disorders. Nevertheless, most of the information reported so far address Caucasian and Asian individuals. Hence, our aim was to conduct a gene‐level association study in Mexican psychiatric individuals diagnosed with suicide attempt. Methods We recruited 192 individuals from two clinical centers in Mexico. All participants were born in Mexico and had Mexican parents and grandparents. Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip. A p‐value lower than 1e‐05 was considered as gene‐level significant and a p‐value lower than 1e‐04 was considered as gene‐level nominal significant. Results Our analyses showed that SCARA5 was associated to suicide intent at a gene‐level with statistical significance (p‐value = 1.12e‐6). Other genes were nominally associated with suicide attempt: GHSR (p‐value = 0.0004), RGS10 (p‐value = 5.13e‐5), and STK33 (p‐value = 3.62e‐5). Regarding gene variant analyses, the SNPs with a statistical association (p > .05) were rs561361616, rs1537577, rs11198999 for RGS10, and rs11041981, rs11041993, rs11041994, rs11041995, rs11041997, rs10840083, rs10769918 for STK33. For these genes, previous studies have associated SCARA5 with depression, GHSR with alcohol dependence and depression, and RGS10 with schizophrenia and depression. To date, STK33 has not been associated with any psychiatric disorder. Conclusion Our outcomes revealed that SCARA5, GHSR, RGS10 and STK33 could be considered as risk biomarkers for suicide attempt behavior in our Mexican psychiatric sample. We recommend to perform larger scale analyses to have conclusive results.