Translational Psychiatry最新文献

{"title":"Altered GABA_B receptor sensitivity in heavy drinkers indexed using a TMS-based biomarker: a randomized controlled experimental medicine trial.","authors":"Chiara Montemitro, Daphne Donahue, Andrea Costumati, Federico Maruottolo, Sara Terezza, Caroline Sjoberg, Irene Perini, Markus Roman, Fredrik C Kugelberg, Markus Heilig","doi":"10.1038/s41398-026-04530-4","DOIUrl":"10.1038/s41398-026-04530-4","url":null,"abstract":"<p><p>Metabotropic γ-aminobutyric acid type B receptors (GABA_BRs) are implicated in alcohol use disorder (AUD) and represent a promising therapeutic target. However, robust biomarkers of GABA_BRs target engagement and sensitivity in humans are lacking. We examined transcranial magnetic stimulation (TMS)-derived cortical inhibition and growth hormone (GH) release as measures of GABA_BR function, and whether heavy alcohol use is associated with altered responses to pharmacological GABA_BR activation. In a randomized, double-blind, placebo-controlled crossover study, 31 healthy volunteers (16 heavy drinkers, 15 light drinkers) received baclofen 30 mg, baclofen 60 mg, or placebo across three sessions. Long-interval intracortical inhibition (LICI), short-interval intracortical inhibition, and intracortical facilitation were assessed with paired-pulse TMS at baseline and ~60 min post-dose. Baclofen blood concentrations and plasma GH levels were measured. Baclofen produced dose-dependent increases in GH release, confirming neuroendocrine GABA_BR engagement. The LICI response to baclofen differed between groups: In light drinkers, baclofen at 30 mg potentiated LICI, and a similar potentiation was seen at 60 mg, indicating that a plateau may have been reached. In contrast, in heavy drinkers, a potentiation of LICI similar to that in light drinkers was seen at 30 mg baclofen, but was absent at the 60 mg dose despite comparable pharmacokinetics, suggesting altered GABA_BR function. Effects were selective for GABA_BR-mediated inhibition, with no consistent modulation of short-interval intracortical inhibition or corticospinal excitability. Acute baclofen administration reveals altered GABA_BR sensitivity in heavy drinkers, with preserved responses at lower doses but reduced response under stronger agonist stimulation. LICI and GH release provide complementary biomarkers of central and peripheral GABA_BRs engagement and may support translational development of mechanism-based treatments for AUD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting trail-making test performance using 7-Tesla structural cerebral MRI.","authors":"Gereon J Schnellbächer, Ravichandran Rajkumar, Tanja Veselinović, Shukti Ramkiran, Jana Hagen, Maria Collee, N Jon Shah, Irene Neuner, Jürgen Dammers","doi":"10.1038/s41398-026-04402-x","DOIUrl":"10.1038/s41398-026-04402-x","url":null,"abstract":"<p><p>Psychopharmaceutical therapy has seen a lack of improvement in efficacy, highlighting the need for a more individualized treatment approach that optimally leverages pharmaceutical effects. To achieve this, it is necessary to identify factors that can predict psychological attributes and treatment outcomes. We hypothesize that brain morphology may serve as a predictor of performance in psychological tests. A 7-Tesla-MRI system was used to measure 74 transdiagnostic patients and 41 healthy controls. Values for grey matter volume (GMV), cortical thickness and gyrification based on the Schaefer 100 Atlas for parcellation were determined. Using this morphological data, performance in a Trail-Making Test (TMT) - A and B was predicted with the help of a deep learning model. A SHAP analysis was conducted to identify the key variables important for the model. The accuracy in predicting TMT performance was very good at 0.795. The most decisive feature influencing predictions was gyrification. Areas indicating inter-group differences were focused in the frontal cortex, as well as in temporal and parietal regions. Morphological characteristics can predict test performance with high accuracy. These results support the implementation of a transdiagnostic approach in clinical practice to better address the underlying pathophysiology. Symptom prediction based on neuroimaging data appears to be an achievable goal.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter signatures of addiction diverge across opioids, cannabis and nicotine and predict impulsive choice in cannabis dependence.","authors":"Richard O Nkrumah, Lea Wetzel, Justin Böhmer, Katharina Eidenmueller, Patrick Bach, Silvia De Santis, Henrik Walter, Wolfgang H Sommer, Gabriele Ende","doi":"10.1038/s41398-026-04491-8","DOIUrl":"10.1038/s41398-026-04491-8","url":null,"abstract":"<p><p>White matter (WM) microstructure is implicated in the neurobiology of substance use disorders (SUDs), yet direct comparisons across substance-dependence syndromes remain scarce. It is also unclear whether WM abnormalities relate to impulsive decision-making and substance use severity. We performed a cross-sectional, dual-centre diffusion MRI study and quantified WM microstructure using diffusion tensor imaging and neurite orientation dispersion and density imaging in 87 individuals with SUDs (48 with cannabis dependence (CUD), 16 with opioid dependence (OUD), and 23 with nicotine dependence (NUD)) and 53 nonsmoking healthy controls. Whole-brain tract-based spatial statistics and tract-specific analyses of the middle longitudinal fasciculus (MLF), a temporo-parietal tract implicated in cognitive control and valuation, were performed. OUD and CUD exhibited convergent, widespread WM abnormalities characterised by reduced fractional anisotropy and increased mean diffusivity and orientation dispersion across fronto-temporo-parietal and limbic pathways, including the superior longitudinal fasciculus, arcuate fasciculus, cingulum, and MLF. In contrast, NUD showed more circumscribed alterations observed primarily in MD and  localised mainly to anterior and callosal white matter regions. In CUD, higher MLF orientation dispersion was associated with steeper delay discounting (r = 0.41, p = 0.011). Moderated mediation analyses indicated that this association was indirectly driven by cannabis consumption, with asignificant conditional indirect effects observed only among daily users. No significant MLF-discounting associations were observed in OUD. Our findings reveal both shared and distinct WM alterations across SUDs and identify a link between MLF microstructure and impulsive choice in cannabis dependence.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world alcohol cue exposure and drinking risk in alcohol use disorder.","authors":"Ali Ghadami, Abhijit Sreepada, Iris Reinhard, Marvin Ganz, Justin Boehmer, Kanya Meyer-Degering, Henrik Walter, Jamila Andoh, Bernd Lenz, Patrick Bach, Falk Kiefer, Emanuel Schwarz, Markus Reichert, Ulrich W Ebner-Priemer, Andreas Meyer-Lindenberg, Christine Heim, Heike Tost","doi":"10.1038/s41398-026-04506-4","DOIUrl":"10.1038/s41398-026-04506-4","url":null,"abstract":"<p><p>Alcohol-related cues are thought to contribute to drinking in alcohol use disorder (AUD), but their contribution in daily life remains difficult to separate from changing social contexts and internal states. We used ecological momentary assessment in two independent cohorts of non-treatment-seeking individuals, comprising a discovery cohort with AUD (17-62 years; n = 73) and a young-adult replication cohort screened for risky drinking (19-35 years; n = 56), to test whether alcohol cue exposure was associated with momentary drinking after simultaneous multivariable adjustment for social context, affective states, and event appraisal. In logistic mixed-effects models, within-person exposure to alcohol-related cues was significantly and reproducibly associated with higher odds of drinking in both cohorts. Being in company, exposure to drinking companions, and higher energetic arousal also showed reproducible within-person associations with drinking. Exploratory clustering of participant-specific slopes suggested meaningful alcohol cue-reactive and social context-reactive risk profile candidates. These findings identify alcohol cue exposure as a robust daily-life correlate of drinking and suggest candidate phenotypes motivating future validation studies of more personalized, context-aware interventions for AUD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell, spatial, and machine learning analyses identify ANKIB1 as an oligodendrocyte-anchored palmitoylation-associated candidate biomarker of Alzheimer's disease.","authors":"Jinshu Liang, Zongtang Xu, Ziting Zhu, Fengchu Liang, Simin Tang, Yingdong Deng, Xiangsheng Zhang, Hao Chen, Yuwan Lin, Jun Zhou","doi":"10.1038/s41398-026-04463-y","DOIUrl":"10.1038/s41398-026-04463-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by progressive neurodegeneration and cognitive decline, yet most candidate therapies targeting amyloid-β have failed to robustly modify disease progression, underscoring an incomplete mechanistic understanding. Oligodendrocytes (ODCs) have recently emerged as active contributors to AD pathology, but the cell-type-specific role of protein S-palmitoylation - a reversible lipid post-translational modification regulating membrane targeting and trafficking - in AD remains uncharacterized. Here we performed an integrated multi-omics analysis combining single-cell RNA sequencing (GSE233208; 48,714 cells), five bulk transcriptomic cohorts (769 samples), and 10× Visium spatial transcriptomic data from 16 brain sections. Palmitoylation activity was quantified at single-cell resolution using a curated 46-gene set; machine learning frameworks (LASSO, random forest, and XGBoost) were used to distil a parsimonious biomarker panel; and four complementary metrics (Jaccard index, overlap coefficient, colocalization percentage, and odds ratio) were applied to evaluate spatial gene-cell colocalization. Oligodendrocytes emerged as the cell population most strongly enriched for palmitoylation activity in the AD brain, supported by per-cell-type scoring, odds ratio enrichment, and an ODC-anchored 658-gene palmitoylation module. Intersection with AD-associated differentially expressed genes yielded 89 candidate genes, from which machine learning identified a seven-gene biomarker panel (ANKIB1, SPAG9, HBP1, SLC25A29, FAM171A1, ATXN10, and NDUFV1). ANKIB1 consistently topped every layer of analysis, with the highest AUC for AD discrimination (0.813, 95% CI 0.782-0.844) and persistent spatial colocalization with ODC-enriched regions across early AD and AD. Network pharmacology nominated AHR and TRIM11 as candidate upstream regulators and catalogued compounds with reported gene interactions. These findings identify the ODC-palmitoylation axis as a previously underappreciated dimension of AD biology and position ANKIB1 as a leading candidate biomarker of ODC dysfunction in AD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct prosocial behaviors associated with persistent symptom trajectories in psychiatric disorders.","authors":"Simon Jangard, Joana B Vieira, Maria Å Garke, Olivia Ojala, Kristoffer N T Månsson, Maria Hedman-Lagerlöf, Karolina Sörman, Samir El Alaoui, Alexander Rozental, David Forsström, Johan Lundin, Shervin Shahnavaz, Tobias Lundgren, Andreas Olsson, Nitya Jayaram-Lindström","doi":"10.1038/s41398-026-04515-3","DOIUrl":"10.1038/s41398-026-04515-3","url":null,"abstract":"<p><p>Prosocial behavior, the tendency to act for others' benefit, is essential for mental health. Although social contexts strongly shape prosocial behavior in healthy individuals, its relevance across psychiatric disorders remains unclear. We examined whether context-dependent prosocial behaviors were associated with baseline psychiatric symptoms and longitudinal symptom trajectories. In a one-year longitudinal cohort study, Swedish adults (n = 4484) with at least one self-reported psychiatric disorder completed standardized questionnaires of six prosocial behavior subtypes at baseline, followed by monthly reports of alcohol use, substance use, anxiety, and depressive symptoms. Latent class linear mixed models identified longitudinal symptom trajectories, and logistic regression models investigated their associations with baseline prosocial behavior subtypes. All models adjusted for demographic covariates and shared variance across psychiatric symptom domains. Three prosocial behavior subtypes showed longitudinal associations with stable psychiatric symptom trajectory classes. Higher anonymous prosociality was associated with lower odds of belonging to the stable high alcohol use trajectory (OR = 0.89, p = 0.013). Higher public prosociality was associated with higher odds of belonging to the stable high substance use trajectory (OR = 1.15, p = 0.036). Higher emotional prosociality was associated with higher odds of belonging to the stable high anxiety trajectory (OR = 1.25, p < 0.001). No prosocial subtype was associated with depressive symptom trajectories. Overall, context-dependent prosocial behaviors were associated with persistent levels of alcohol use, substance use, and anxiety symptoms. These findings suggest that specific prosocial behaviors may refine transdiagnostic models of social dysfunction by indexing stable patterns of psychiatric symptom burden.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surveying alternative transcripts of disease-associated genes and their cell type specificity - a case study with ANK3.","authors":"Martin Falck, Denis Reis de Assis, Asbjørn Holmgren, Ragnhild Aaløkken, Sarah Åsheim, Hans-Christian Aass, Knut Tomas Dalen, Srdjan Djurovic, Timothy Hughes","doi":"10.1038/s41398-026-04412-9","DOIUrl":"10.1038/s41398-026-04412-9","url":null,"abstract":"<p><p>The ANK3 gene has been conclusively linked to bipolar disorder, but its role in disease etiology remains unclear: both the specific transcript and its expressing cell type remain unclear. This is a near-universal problem for genes associated with polygenic neuropsychiatric disorders. One of the causes of this unfortunate stasis is that human transcript databases have an incomplete list of alternative isoforms of genes and that it is technically challenging to identify the cell-types in which they are expressed. Here, we address this knowledge gap for ANK3. ANK3 is a useful case study because of its rich alternative splicing and important neurobiological role in neurons and oligodendrocytes. We used Oxford nanopore sequencing of full-length transcripts to identify all human and mouse ANK3 exons. Then, we isolate and sort brain nuclei and use droplet-digital PCR to measure cell-type specific expression of alternatively spliced exons. We confirm that RefSeq transcript annotations of ANK3 lack many of the alternatively spliced exons and we show that, despite being lowly expressed, these exons are highly evolutionarily conserved and have strong cell type specificity. Elucidating psychiatric disorder etiology will require an overview of the transcripts of all the disorder-associated genes and the cell types in which these transcripts are expressed. This work on ANK3 illustrates the extent to which such information is currently lacking, ways in which the information can be acquired, and the technical challenges that are encountered in the process.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered semantic prediction error processing with increasing schizotypal and autistic traits.","authors":"Elisabeth F Sterner, Verena F Demler, Rachel Lenz, Lucy J MacGregor, Christoph Mathys, Franziska Knolle","doi":"10.1038/s41398-026-04479-4","DOIUrl":"https://doi.org/10.1038/s41398-026-04479-4","url":null,"abstract":"<p><p>Predictive processing has been proposed as a framework for symptom development in autism (ASD) and schizophrenia (SSD) spectrum disorders, with ASD being associated with an overweighting of (low-level) sensory evidence whereas SSD is characterized by an overweighting of (high-level) prior beliefs, both resulting in altered prediction error processing. This study investigated these hypotheses and their electrophysiological correlates in subclinical expressions of ASD and SSD during language processing. Participants completed an auditory comprehension task that manipulated the precision of high-level semantic prior beliefs and low-level sensory evidence. Hierarchical Bayesian belief-updating modeling and electroencephalography were used to examine whether imbalances in the weighting of prior beliefs and sensory evidence were reflected in altered processing of semantic prediction errors, characterized by mean N400 amplitudes. Computational modeling revealed that increasing schizotypal traits were associated with significant overweighting of prior beliefs, while autistic traits did not show a significant shift. Linear mixed-effect models of mean N400 amplitudes indicated that schizotypy-related overweighting of semantic prior beliefs was reflected in a reduced semantic prediction error signal, indexed by smaller N400 differences between high predictability sentences and both low predictability and high predictability mismatch sentences. A similar but weaker and less distinct pattern emerged for increasing autistic traits. These findings provide converging computational and electrophysiological support for overweighting of semantic prior beliefs with increasing subclinical schizotypy. In contrast, increasing autistic traits were not associated with overweighting of sensory evidence, with electrophysiological results instead suggesting subtle alterations in the weighting of semantic prior beliefs.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying a structural brain network for social anxiety: connectome-based predictive modeling and network analyses in a transdiagnostic sample.","authors":"Hannah Meinert, Marius Gruber, Emilia D E Brügge, Lisa Brüwer, Lisa Sindermann, Alexandra Winter, Theresa M Slump, Fabian Breuer, Elisabeth Schrammen, Susanne Meinert, Janik Goltermann, Dominik Grotegerd, Jonathan Repple, Ronny Redlich, Linda M Bonnekoh, Jochen Bauer, Udo Dannlowski, Joscha Böhnlein, Elisabeth J Leehr","doi":"10.1038/s41398-026-04466-9","DOIUrl":"10.1038/s41398-026-04466-9","url":null,"abstract":"<p><p>Trait social anxiety (SA) is continuous and can manifest across the entire spectrum of mental health, from subclinical levels in healthy controls to burdensome manifestations in major depressive disorder and finally full-blown disorders like social anxiety disorder (SAD). Although it has been proposed that SA is associated with deviations in the structural connectome, there is little research on the SA spectrum and its relation to abnormalities in brain structural networks. In this study, we aim to identify a structural brain network for SA across diagnostic groups using a transdiagnostic sample and connectome-based predictive modeling (CPM) to provide insight on neurostructural underpinnings of the SA spectrum. We collected magnetic resonance imaging (MRI) and clinical data of N = 160 participants across an SA spectrum. Diffusion-weighted and T1-weighted structural images were used to reconstruct each participant's structural connectome. We applied CPM to identify a structural brain network that predicts SA across diagnostic groups. We further analyzed the structural connectome to investigate hubs and differences in global graph metrics between participants with and without SAD (noSAD n = 96, SAD n = 64). CPM revealed a brain network with 46 edges predicting SA across the SA spectrum with mean r = 0.141 (CI = [0.12, 0.2], p = 0.003). Hubs were located in the left pericalcarine, inferior-parietal, superior-parietal, right lateral-occipital cortex and pars orbitalis. This study provides first evidence for a shared neurobiological foundation of SA across diagnostic groups and points towards a transdiagnostic relevance of SA and the related brain network.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A machine learning-based ecological momentary intervention for mental health promotion in youth: a micro-randomized trial.","authors":"Christian Rauschenberg, Frederike Schirmbeck, Janik Fechtelpeter, Eva Wierzba, Selina Hiller, Katharina Kahr, Anna Kessler, Lale Hornbacher, Christian Goetzl, Anita Schick, Daniel Durstewitz, Silvia Krumm, Georgia Koppe, Ulrich Reininghaus","doi":"10.1038/s41398-026-04475-8","DOIUrl":"10.1038/s41398-026-04475-8","url":null,"abstract":"<p><p>Ecological Momentary Interventions (EMIs) using machine learning (ML)-based assignment algorithms may improve mental health outcomes by delivering more person-tailored content, but evidence is pending. The study aimed to determine whether ML-based assignment of EMI components augments effects on momentary mental health outcomes when compared to random assignment in youth from the general population and psychological counselling services. A within-subject micro-randomized trial was conducted. Participants were randomly assigned up to seven times daily (1:1 ratio; up to 210 decision points) to either an ML-based (experimental condition) or a random (active control condition) assignment of EMI components. Proximal outcomes were time-lagged changes in positive affect, momentary resilience, and negative affect at t_n+1. Feasibility and safety were assessed. Distal outcomes included psychological distress, resilience, and emotion regulation. A total of 49 youths (mean age 20.6; 78% female) were included. At baseline, participants reported mild-to-moderate psychological distress on average (K10 mean = 23.8, SD = 7.1), with more than one third reporting moderate or severe distress. An initial, outcome-specific signal favoring ML-based over random assignment was observed for momentary resilience (B = 0.147, 95% confidence interval (CI), 0.004 - 0.290, p = 0.044), whereas there was no evidence of beneficial effects on positive or negative affect. Feasibility indicators supported delivery of the AI4U training, with favorable ratings of satisfaction, acceptability, and usability; no serious adverse events were reported. Uncontrolled pre-post comparisons suggested a small reduction in psychological distress (d = -0.23) and improvements in resilience (d = 0.55) and adaptive emotion regulation (d = 0.53). Taken together, this study demonstrates the feasibility and preliminary safety of a ML-based adaptive EMI in youth and provides an initial, outcome-specific signal that ML-based assignment may improve momentary resilience relative to random assignment, whilst underscoring the need for larger, adequately powered MRTs and formal validation of whether forecasting performance translates into policy value.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}