Introduction and objectivePopulations at high altitude (HA) face a higher incidence and severity of traumatic brain injury (TBI). This pilot study utilized longitudinal 1H-MRS to identify neurochemical biomarkers of HA adaptation and the subsequent metabolic response to mild TBI (mTBI).MethodsMale C57BL/6J mice were exposed to simulated HA (5,000 m) or sea level (SL) for 12 weeks. Following adaptation, a unilateral mTBI was induced via closed head injury (CHI). Mice were then monitored for an additional 2 weeks at HA (total duration of 14 weeks). In vivo1H-MRS spectra (7 T) were collected from the frontal cortex, hippocampi, and cerebellum at weeks 0, 4, 12 to assess HA adaptation. Following the CHI, subsequent measurements were collected at week 12 (post-injury) and week 14 to monitor longitudinal neurochemical responses to the mTBI.ResultsChronic HA exposure induced significant reductions in myo-inositol (Ins) and total choline (tCho) in the hippocampus, establishing a baseline of metabolic fragility that sensitized the brain to subsequent traumatic insult. Post-mTBI, the HA group exhibited a profound “metabolic crisis,” characterized by significantly lower tCho and failed recovery of total N-acetylaspartate (tNAA) compared to SL controls. Total creatine (tCr) was the most acutely affected metabolite, underscoring a depletion of the bioenergetic reserve.ConclusionChronic hypobaric hypoxia fundamentally alters baseline brain metabolism and impairs the neurochemical recovery from mTBI. These findings suggest that standard recovery protocols may be insufficient for HA-adapted populations and highlight 1H-MRS as a critical tool for detecting “invisible” metabolic vulnerability in extreme environments.
Disrupted sleep-wake cycles and circadian rhythms in a Drosophila model of C9orf72-FTD
Frontotemporal dementia (FTD) is a neurodegenerative disorder that affects behavior, personality, motor activity, speech, cognition, and sleeping patterns. Previous findings support the idea that disruption of sleep and circadian systems may not only be affected by this disease but also work to actively shape the clinical phenotype of FTD. Thus, understanding how sleep-wake cycles are altered may provide insight into mechanisms that influence both disease progression and quality of life. We studied an established Drosophila model of FTD to investigate changes in the sleep-wake cycle of both young and aging flies. A C9orf72-associated FTD model was chosen, as the most common genetic cause of sporadic and hereditary FTD is a hexanucleotide repeat expansion in intron 1 of the C9orf72 gene. We performed behavioral assays to measure locomotor activity in both a 12 h:12 h light/dark (LD) cycle and complete darkness (free running). From this data, we were able to analyze changes in sleep and activity patterns, as well as circadian rhythms in flies modeling C9orf72-FTD. Our data suggests that these flies have increased nighttime activity and decreased sleep at night, which becomes more significant as they age. Older flies also displayed decreased sleep pressure during both day and night and lost rhythmicity. Of specific interest, young flies modeling C9orf72-FTD demonstrated altered day and night sleep latency, decreased sleep depth at night, and reduced rhythmicity in constant darkness. This suggests that changes in their sleep-wake cycle occur early in disease progression and provide an avenue for potential intervention and early diagnostic markers.
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
Large-scale meta- and cross-trait analyses uncover shared genetic risk factors for IBS and psychiatric disorders
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.
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.
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.
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.
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.