IntroductionIrritable bowel syndrome (IBS) is a common gut-brain axis disorder characterized by abdominal pain and altered bowel habits, and it shows high comorbidity with psychiatric disorders. However, the shared genetic mechanisms underlying these associations remain incompletely understood.MethodsWe performed a large-scale meta-analysis of IBS in individuals of European ancestry by integrating genome-wide association study (GWAS) summary statistics from the UK Biobank, Bellygenes, and the Million Veteran Program (MVP), thereby increasing statistical power to detect novel IBS loci. We further conducted global genetic correlation analyses with psychiatric traits, followed by multi-trait analysis of GWAS (MTAG) and conditional false discovery rate (condFDR) analyses to identify pleiotropic loci. Transcriptomic, methylomic, and expression quantitative trait locus (eQTL) data were integrated to explore potential regulatory mechanisms.ResultsThe meta-analysis identified up to ten previously unreported IBS loci, several of which were supported by colonic and brain eQTL effects. Global genetic correlation analyses confirmed substantial genetic overlap between IBS and psychiatric traits, particularly major depressive disorder and neuroticism. MTAG and condFDR analyses uncovered more than 100 pleiotropic loci, including signals at SORCS1, SLC35D1, COA1, and TLE1. Integrative analyses of transcriptome- and methylome-wide data highlighted regulatory mechanisms spanning colonic, immune, and neuronal tissues, supporting neuro-immune crosstalk and mitochondrial involvement.DiscussionOur findings provide a comprehensive genetic characterization of IBS, refine its heritable basis, reveal pleiotropic links with psychiatric disorders, and implicate molecular pathways across the gut-brain axis. These results advance mechanistic understanding of IBS and may inform future therapeutic development for IBS and its psychiatric comorbidities.
Can the treatment effects of human-animal interaction be maintained? A randomized controlled trial including follow-up in people with severe mental illness
IntroductionThere are persistent demands for well-designed randomized controlled trials (RCTs), including follow-up measurements, in studies on animal-assisted treatment (AAT). In addition, a possible dose-response relationship is under discussion. The aim of the present study was to investigate the efficacy of a single-session AAT with sheep, including a booster exercise, over a follow-up period of four weeks.MethodsIn an RCT, a single-session AAT with sheep in a group setting, including an imaginative booster exercise conducted in the week following the AAT session, was compared to treatment as usual (TAU). Sixty psychiatric inpatients with severe mental illness were assessed for positive and negative emotions, mindfulness, and self-efficacy expectancy at baseline (PRE), immediately after the intervention (POST), and at one-week and four-week follow-ups.ResultsThe results indicate significant differences between the two groups at POST and still in the one-week follow-up (FU1) in three of four outcomes. Within the intervention group, within-group analyses demonstrated significant improvements from PRE to POST and from PRE to FU1 across all outcomes, with large effect sizes. At the four-week follow-up, all significant effects had diminished.ConclusionsAn imaginative booster exercise conducted within one week after an AAT session was effective in maintaining large effect sizes for up to one week. However, the results did not persist at the four-week follow-up. Longer follow-up periods, variations in the number of sessions, and the inclusion of active control groups are therefore necessary for further AAT studies.Trial registrationhttps://drks.de/search/de/trial/DRKS00031347, identifier DRKS 00031347
Recognizing anxiety and depression in cancer patients based on speech and facial expressions
PurposeTo address the anxiety and depression experienced by cancer patients due to the stress of diagnosis and treatment, as well as the limitations of traditional assessment methods characterized by high subjectivity and low efficiency, this study aims to develop a multimodal fusion approach for the simultaneous and precise evaluation of these two psychological states.Patients and methodsA speech-video dataset of clinically diagnosed cancer patients was used. This study proposes a multimodal fusion approach: for depression recognition, We employ the HuBERT pre-training architecture based on Transformers, integrating specific acoustic features of depression with textual content to achieve accurate classification of depression through a voice-text modality. For anxiety recognition, a multi-task convolutional neural network is designed to infer anxiety status from the facial expressions.ResultsExperiments conducted on a speech-video dataset of clinically diagnosed cancer patients demonstrates that the multimodal fusion model achieves a depression recognition F1 value of 0.85 and an anxiety recognition F1 value of 0.74, significantly outperforming the unimodal model.ConclusionThe results of the two modalities are fused by decision-level weighted averaging to realize the simultaneous assessment of anxiety and depression in cancer patients. The study may provide technical support for rapid, noninvasive screening of psychological status in cancer patients.
Cortical high-threshold and low-activation characteristics in adolescent depression: a cross-age differential analysis
BackgroundAdolescent depression exhibits distinct neurophysiological features, with marked age heterogeneity particularly in the resting motor threshold (RMT) measured during repetitive transcranial magnetic stimulation (rTMS), and substantial variability in clinical therapeutic efficacy. Functional near-infrared spectroscopy (fNIRS) enables the assessment of cortical excitability levels; however, research investigating the association between RMT and cortical activation in adolescent patients with depression remains limited. This study aims to elucidate the underlying neural mechanisms from the perspective of cortical hemodynamics, which is crucial for further optimizing neuromodulation strategies in patients with depression.MethodsWe collected data from 85 treatment-naive patients with depression who underwent rTMS therapy. All patients completed RMT measurement, fNIRS examination, and Hamilton Depression Rating Scale (HAMD) assessment prior to rTMS treatment. Participants were divided into three groups according to age: the adolescents group (n=31), the young adult group (n=26), and the middle-aged group (n=28). We compared the differences in RMT among the three groups and explored the relationships between RMT, cortical activation (reflected by prefrontal oxyhemoglobin level changes during the verbal fluency task via fNIRS), and depression severity (assessed by HAMD scores).ResultsThe results demonstrated that the adolescents group had a significantly higher RMT than the other age groups (58.00 ± 11.14, P < 0.001), accompanied by the lowest prefrontal Oxy-Hb activation level (0.095 ± 0.06, P < 0.001). A strong negative correlation was observed between RMT and cortical activation (Spearman’s rs= -0.929, P < 0.001), while a strong positive correlation was found between RMT and depression severity (Spearman’s rs = 0.837, P < 0.001). The distinct coupling phenomenon of high threshold-low activation-severe symptoms was most prominently manifested in this age group, which may theoretically reflect an underlying dysregulation in broader emotional networks, though the current direct findings strictly indicate localized alterations in prefrontal activation and motor cortical excitability.ConclusionsThe characteristics of high RMT and low cortical activation in adolescent depression serve as important neurobiological markers for depression severity. This finding provides a novel direction for developing individualized, developmentally tailored neuromodulation strategies (e.g., optimization of rTMS targets and dosages), indicating that interventions for adolescent depression should prioritize promoting the healthy integration of emotional circuits and the functional coordination between the cortex and subcortex.
Getting the timing right. Autistic adolescents reflect on the value of an early diagnosis
IntroductionIn Western countries, autism diagnoses are increasingly assigned in the first years of life. But is earlier necessarily better? Despite potential benefits, autistic infants and toddlers cannot participate in these discussions. In the ethical debate on early autism diagnosis, this raises tensions between parental duties and rights, and the child’s developing autonomy.MethodsTo mend the lack of autistic voices in this debate, we queried a diverse group of 18 autistic adolescents (aged 16–18). In a set of indepth interviews, we explored their experiences of their autism diagnosis, and their views on the ideal timing of such a diagnosis, if at all.ResultsUsing the QUAGOL data-analysis method, we developed three themes: (1) (Not) feeling different, (2) Drawing up the balance of the label’s value, and (3) Getting the timing right. Adolescents experiencing most difficulties in navigating the neurotypical world also seemed to value the diagnostic label most, and vice versa. Nevertheless, nearly all adolescents favored a relatively early diagnosis and early disclosure thereof—not necessarily in infancy, but early enough to enable timely support for both themselves and their parents. Crucially, adolescents emphasized that such early support should be personalized, readily available and neurodiversity-affirmative to make early diagnosis truly worthwhile.DiscussionOur data did not corroborate any presumed clash of interests between parents and autistic children. Consequently, we suggest moving this ethical debate away from a discourse based on individual rights or interests toward a relational, care ethics approach.
Advancing conversational diagnostic AI with multimodal reasoning
Nature Medicine, Published online: 14 May 2026; doi:10.1038/s41591-026-04371-0
Improvements in the Articulate Medical Intelligence Explorer, a large language model designed for diagnostic dialogue, enable the model to request, interpret and reason about multimodal medical data.
Performance of traumatic encephalopathy syndrome criteria in identifying individuals with chronic traumatic encephalopathy
Nature Medicine, Published online: 14 May 2026; doi:10.1038/s41591-026-04392-9
The proposed clinical features of traumatic encephalopathy syndrome have low predictive value for chronic traumatic encephalopathy pathology, raising significant concern for incorrect diagnoses of neurodegeneration in former athletes.
Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial
Nature Medicine, Published online: 14 May 2026; doi:10.1038/s41591-026-04395-6
Subcutaneous injections of abatacept were superior to oral hydroxychloroquine in preventing progression to persistent arthritis in individuals with palindromic rheumatism.
Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming
Nature Neuroscience, Published online: 14 May 2026; doi:10.1038/s41593-026-02300-5
This study reveals that the immune system has a role in driving ALS. These findings link blood immune changes to spinal cord damage and suggest personalized treatments targeting specific immune pathways.
Synchronous climbing fiber activity enables instructive signaling for cerebellar learning through modulation of disinhibitory circuits
Nature Neuroscience, Published online: 14 May 2026; doi:10.1038/s41593-026-02268-2
Combining connectomics, physiology and behavior, this study shows how the cerebellum decides when to learn. Synchronized climbing-fiber error signals lift an inhibitory signal gate on Purkinje cells, enabling synaptic plasticity and motor adaptation.