Camila Marcelino Loureiro

SIRS 2026, held under the theme “Schizophrenia Research in the Era of Artificial Intelligence,” brought together researchers, clinicians, and persons with lived experience to take stock of a field whose tools for measuring, predicting, and intervening in psychosis have expanded rapidly. Themes spanned artificial intelligence, automated speech analysis, retinal imaging, computational modelling, and novel psychosocial and pharmacological targets, with evidence that, individually, warrants cautious but serious attention and that, collectively, points toward a more mechanistically grounded psychiatry. A recurring call across the meeting was for rigorous external validation, equitable implementation, and sustained scrutiny of underlying assumptions, including whether existing diagnostic categories and treatment targets remain adequate. Some areas remained underworked relative to their importance, including translating basic neuroscience advances into questions relevant to patients and families, and the structural determinants of illness onset and treatment access. Perhaps the most significant development at SIRS 2026 was not any single scientific finding but the broadening of whose voices and experiences are treated as evidence worth taking seriously in this era of AI, a shift whose consolidation remains a question for the field as much as for any individual programme of work.

Introduction: Genetic factors are thought to play an important role in antipsychotic-induced weight gain (AIWG). This study conducted a meta-analysis of current research of the pharmacogenetic associations of adult AIWG. Methods: The analysis included papers providing comparisons of weight gain across at least two allele combinations for at least one single nucleotide polymorphism (SNP). Inclusion criteria were, patients 18 years of age or older and had received a diagnosis of severe mental illness, for which antipsychotic medication was prescribed. The association with AIWG needed to be replicated across at least two papers reporting separate sample sets. Results: Two hundred twenty-three papers were assessed for eligibility. Of the 223 papers, 148 were excluded, leaving 75 studies to be included. Six SNPs in six different genes were identified as having significant associations ( p < 0.05) with AIWG. These were HTR2C rs3813929 (TT + TC vs CC), Hedge’s g 0.76; MTHFR rs1801133 (TC + TT vs CC), Hedge’s g 0.61; ADRA2A rs1800544 (CC + CG vs GG), Hedge’s g 0.71; MC4R rs489693 (CC + AC vs AA) Hedge’s g 0.127; LEPR rs1137101 (GG + AG vs AA) Hedge’s g 0.18 and CNR1 rs104935 (GG + AG vs AA), Hedge’s g 0.55. Conclusion: The study identified six SNPs that predispose adult individuals to AIWG, with HTR2C rs3813929 and ADRA2A rs1800544 showing the largest effect sizes. Five of these have a role in hypothalamic regulation of appetite/satiety. Identification of these risk-associated SNPs may assist the development of a polygene/polyphenotypic risk score to identify individuals with psychosis who are at heightened risk of experiencing AIWG.

Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome is a disease of uncertain aetiology that affects up to 400,000 individuals in the UK. Exposure of cultured cells to the sera of people with ME has been proposed to cause phenotypic changes in these cells in vitro when compared to sera from healthy controls. ME serum factors causing these changes could inform the development of diagnostic tests. In this study, we performed a large-scale, pre-registered replication of an experiment from Fluge et al (2016) that reported an increase in maximal respiratory capacity in healthy myoblasts after treatment with serum from people with ME compared to serum from healthy controls. We replicated the original experiment with a larger sample size, using sera from 67 people with ME and 53 controls to treat healthy cultured myoblasts, and generated results from over 1,700 mitochondrial stress tests performed with a Seahorse Bioanalyser. We observed no significant differences between treatment with ME or healthy control sera for our primary outcome of interest, oxygen consumption rate at maximal respiratory capacity. Results from our study provide strong evidence against the hypothesis that ME blood factors differentially affect healthy myoblast mitochondrial phenotypes in vitro .

Over the past 15 years, genetic studies of psychiatric disorders have provided important insight into the contribution of both common variants of small effect, as well as rare exonic and copy number variants with large effect sizes. Genome‐wide association studies (GWAS) allow us to understand the intricate polygenicity characteristic of many psychiatric disorders. However, a considerable proportion of single nucleotide polymorphisms (SNPs) implicated in these disorders localize to the non‐coding regions of the genome. Unraveling the molecular mechanisms that underlie the etiology of psychiatric illnesses requires integration using functional genomics approaches. Functional genomics methods are critical for developing a mechanistic understanding of genetic findings in psychiatric disorders. Unfortunately, most studies on psychiatric genetics have focused on individuals of European ancestry, which limits our understanding to only a portion of the population. This further contributes to the underrepresentation of other groups, including individuals from Latin America, in genomic studies and restricts our biological insight into these disorders in these populations. To address this issue, we performed an advanced scoping review to ascertain the landscape of functional genomics psychiatric research in Latin American populations. After analyzing over 1380 papers using our search terms, 52 original papers were identified considering individuals of Latin American origin in psychiatric functional genomics research. The majority of these focused on schizophrenia ( N = 7), bipolar disorder ( N = 7), or a combination of various disorders encompassed in one study ( N = 6). DNA methylation techniques were predominant (73%), followed by gene expression (17%) and other techniques. Most samples were from Brazilian (55.8%) or Mexican (21.2%) participants, followed by “Hispanic” (15.3%), Colombian (5.8%), and Costa Rican (1.9%). Although new psychiatric and functional genomics research, including work from the Latin American Genomics Consortium, is expanding our understanding of the genetic basis of these disorders, significant gaps remain. Increasing the representation of samples from admixed and diverse ancestral backgrounds—such as Latin Americans—in future functional genomics studies is greatly needed. This will broaden the applicability of emerging research to a more diverse population and improve the potential impact of psychiatric genetics research on future precision medicine applications.

Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome is a disease of uncertain aetiology that affects up to 400,000 individuals in the UK. Exposure of cultured cells to the sera of people with ME has been proposed to cause phenotypic changes in these cells in vitro when compared to sera from healthy controls. ME serum factors causing these changes could inform the development of diagnostic tests. In this study, we performed a large-scale, pre-registered replication of an experiment from Fluge et al (2016) that reported an increase in maximal respiratory capacity in healthy myoblasts after treatment with serum from people with ME compared to serum from healthy controls. We replicated the original experiment with a larger sample size, using sera from 67 people with ME and 53 controls to treat healthy cultured myoblasts, and generated results from over 1,700 mitochondrial stress tests performed with a Seahorse Bioanalyser. We observed no significant differences between treatment with ME or healthy control sera for our primary outcome of interest, oxygen consumption rate at maximal respiratory capacity. Results from our study provide strong evidence against the hypothesis that ME blood factors differentially affect healthy myoblast mitochondrial phenotypes in vitro .

Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma.Methods: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 communitybased controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software.Results: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p 4 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis.Conclusion: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.