Translational Psychiatry最新文献

{"title":"Algorithmic loops and the developing brain: a narrative review of dopaminergic mechanisms, sleep disruption, and neuroplasticity.","authors":"Shihshuan Fang, Shenghan Chen","doi":"10.1038/s41398-026-04340-8","DOIUrl":"https://doi.org/10.1038/s41398-026-04340-8","url":null,"abstract":"<p><p>Generation Alpha (born ~2010-2024) is the first cohort whose critical windows of dopaminergic maturation overlap entirely with mass exposure to AI-optimised short-form looping video platforms. Despite a robust epidemiological signal linking social media to depression, anxiety, attention deficits, and sleep disruption in youth, direct causal neurobiological data remain absent. This narrative review synthesises evidence from developmental neuroscience, mesolimbic dopamine physiology, sleep medicine, and longitudinal neuroimaging cohorts to articulate a mechanistic framework: chronic exposure to algorithmically engineered variable ratio reinforcement schedules may produce homeostatic D2/D3 receptor downregulation in the developing striatum, functionally analogous to the neuroadaptations observed in substance use disorders. This deficit state, characterised by anhedonia and acquired attentional dysregulation, is plausibly amplified by algorithmic disruption of slow-wave sleep-the biological window for glymphatic metabolite clearance and synaptic homeostasis. Converging evidence from the Adolescent Brain Cognitive Development (ABCD) Study documents associations between screen behaviour and grey matter volume, reward-circuit activation, and executive function trajectories across early adolescence. Because direct in vivo measurement of D2 receptor density in children using PET radioligands is ethically prohibited, we propose a cross-species, multimodal longitudinal research framework. This integrates a novel nonhuman primate digital self-administration paradigm with human cohort studies utilising computational phenotyping of algorithmic dosage, polysomnographic sleep monitoring, and annual reward-task fMRI. Current evidence justifies both urgent regulatory action and a dedicated research programme to characterise the neurobiological consequences of a uniquely 21st-century exposure.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149288856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-agent large language model framework for structured clinical interviewing and psychiatric screening: a proof-of-concept.","authors":"Mohammad Amin Kamaleddin, Mina Mirjalili, Reza Barzegar, Nghia Trung Le, Areez Visram, Fatemeh Gholami Nezhad, Alice Rueda, Bazen Gashaw Teferra, Candice Monson, Tristan Glatard, Sri Krishnan, Divya Sharma, Benoit Mulsant, Venkat Bhat","doi":"10.1038/s41398-026-04335-5","DOIUrl":"https://doi.org/10.1038/s41398-026-04335-5","url":null,"abstract":"<p><p>Structured psychiatric interviews improve diagnostic reliability but are resource-intensive to administer. We developed a multi-agent large language model (LLM) framework to support protocolized structured interviewing and module-level psychiatric screening. The system orchestrates four agents, Questioner, Evaluator, Navigator, and Diagnoser, to administer interview modules, interpret free-text responses, enforce bounded clarification loops, identify safety-related red flags and trigger escalation, and apply encoded decision rules to produce screening outcomes. Prior to any model processing, responses undergo automated redaction of personally identifiable and protected health information. We conducted a simulation-based technical evaluation using 1350 interviews across 15 neuropsychiatric screening modules (e.g., anxiety, depression, and bipolar disorders) with systematic variation in symptom direction, disclosure depth, and emotional tone. To test robustness to language variability, we additionally evaluated reconstructed conversation bundles derived from the deidentified MentalChat16K dataset. In the primary evaluation, module-level decisions showed 87.8% concordance with rule-based expected outcomes (95% CI: 85.9-89.6), with sensitivity 88.9% (95% CI: 86.5-91.2) and specificity 86.7% (95% CI: 84.0-89.2) relative to predefined item-level endorsements. Post hoc comparator analyses showed higher F2 for the multi-agent framework (88.5%) than single-pass LLM (49.5%) or deterministic rule-based (61.9%) transcript-scoring baselines. On a 2000-sentence red flag benchmark stratified by explicit/implicit and active/passive ideation, the classifier achieved 93.9% accuracy, 94.2% sensitivity, and 93.6% specificity. In pilot feedback from mental health clinicians, descriptive ratings suggested favorable perceptions of clarity, workflow fit, and perceived safety for clinician-supervised use. These results support proof-of-concept technical feasibility for a protocol-adherent, auditable agentic LLM framework for structured psychiatric screening.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149288816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A canonical microcircuit for estimating Excitation/Inhibition (E/I) balance.","authors":"Daniel J Hauke, Julia Rodriguez-Sanchez, Hope Oloye, Lioba C S Berndt, Dimitris A Pinotsis, Karl J Friston, Daniel H Mathalon, Rick A Adams","doi":"10.1038/s41398-026-04312-y","DOIUrl":"https://doi.org/10.1038/s41398-026-04312-y","url":null,"abstract":"<p><p>Excitation/inhibition (E/I) balance is crucial for maintaining healthy brain function and can be disrupted in various neurological and psychiatric disorders. Despite its importance, there are few tools to study E/I balance non-invasively in humans. Here, we propose a canonical microcircuit model to estimate E/I balance from non-invasive magnetoencephalography (MEG), electroencephalography (EEG) or optically pumped magnetometers (OPM) recordings by parameterising global pyramidal and inhibitory cell excitability. We first establish that E/I parameters are identifiable and recoverable. We then explore the effects of these new parameters and their interaction with other parameters in a series of simulations. To highlight the clinical relevance of this new model, we simulate changes in E/I balance and their impact on event-related potentials (ERPs) derived from paired-click, passive and active oddball paradigms, which are among the most robust clinical biomarkers of schizophrenia. Our simulations show that a loss of pyramidal cell excitability can explain reduced ERP amplitudes across all three paradigms, mirroring empirical findings in schizophrenia. This method may serve as a computational assay for estimating synaptopathy and E/I balance from non-invasive electrophysiological recordings across various clinical conditions thereby advancing efforts to develop personalised interventions to restore E/I balance.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149288891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experience sampling reveals habitual and transdiagnostic properties of compulsivity.","authors":"Vanessa Teckentrup, Celine A Fox, Kelly R Donegan, Eoghan Gallagher, Anna K Hanlon, Naomi A Fineberg, Ilenia Pampaloni, Laura A Berner, Claire M Gillan","doi":"10.1038/s41398-026-04350-6","DOIUrl":"https://doi.org/10.1038/s41398-026-04350-6","url":null,"abstract":"<p><p>Both obsessive thoughts and an urge to act have been linked to compulsions cross-sectionally. However, prominent theories of compulsivity disagree quite fundamentally about whether compulsions are goal-oriented attempts to reduce or eliminate obsessive thoughts or are urge-driven and habitual. To shed light on this debate, we used multilevel vector autoregression modelling to analyse contemporaneous and temporal associations based on self-report symptoms and cognition from N = 179 individuals with and without diagnoses who performed compulsions. Six weeks of three-times daily timeseries data with a mean lag of five hours between assessments were gathered from a transdiagnostic sample who checked their phone compulsively, binge ate, or engaged in compulsions commonly seen in OCD (e.g. checking, cleaning). Across compulsions, the strongest within-person correlate of compulsions were urges (β = 0.61, p_FDR < 0.001) and this was 3 times larger than obsessive thoughts and 4 times larger than anxiety. We found that urges predicted compulsions at the next assessment time point (β = 0.09, p_FDR < 0.001), while compulsions themselves had a markedly low tendency to predict themselves (β = 0.04) compared to the other mental health symptoms sampled (0.12 < β < 0.23). Finally, like habits, compulsions occurred more often when executive functioning was low (β = 0.09, p_FDR < 0.001). Based on real-time dynamics of compulsions, we find that urges, but not obsessive thoughts, predict compulsivity five hours later. Intriguingly, the associations were remarkably similar across compulsions, supporting the notion that transdiagnostically, a habit-like mechanism may underlie compulsive actions.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149288813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleus transcriptomics reveals disrupted pathways in the prefrontal cortex of Scn2a-deficient mice.","authors":"Ye-Eun Yoo, Zaiyang Zhang, Purba Mandal, Zhengkuan Tang, Jingliang Zhang, Xiaoling Chen, Morgan Robinson, Muriel Eaton, Brody Deming, Manasi Halurkar, Harish Kothandaraman, Luke C Dabin, Boyu Jiang, Hongyu Gao, Chongli Yuan, Nadia Lanman, Yunlong Liu, Jungsu Kim, Priyanka Baloni, Yang Yang","doi":"10.1038/s41398-026-04348-0","DOIUrl":"https://doi.org/10.1038/s41398-026-04348-0","url":null,"abstract":"<p><p>Loss-of-function variants in SCN2A, which encodes the Na_V1.2 sodium channel critical for action potential initiation and backpropagation, are associated with autism spectrum disorder (ASD) and epilepsy. To investigate SCN2A deficiency-related phenotypes, we developed a preclinical mouse model with severe Na_V1.2 deficiency, which exhibits robust behavioral abnormalities related to autism and epilepsy. However, the neuronal populations and molecular alterations in the mouse model have not been investigated at single-cell resolution. In this study, we performed single-nucleus RNA sequencing (snRNA-seq) in wild-type (WT), homozygous Scn2a-deficient (HOM), and Scn2a-restored HOM (HOM-FlpO) mice. We then examined how Scn2a expression levels affect cellular composition and gene expression profiles in the medial prefrontal cortex (mPFC), a brain region implicated in ASD. Intriguingly, we observed an increased population of immature GABAergic neurons in adult HOM mice, whereas this population is nearly absent in adult WT mice. Differential expression analysis of GABAergic and glutamatergic neurons across genotypes also revealed widespread changes in genes associated with neurotransmitter regulation and synapse organization. Analysis of the HOM-FlpO data identified genes that were significantly altered in HOM mice and were restored toward WT levels following adult Scn2a restoration. Together, these results indicate that reduced Scn2a expression disrupts global transcriptomic profiles across multiple neural cell types, providing insight into cell-type-specific mechanisms underlying SCN2A-related disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149288871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared and disorder-specific computational mechanisms of interference and response inhibition in schizophrenia and major depressive disorder.","authors":"Tongyi Zhang, Sirui Wang, Haoyang Shi, Jia Li, Xiaolong Yang, Jin Jiao, Xiaoning Huo, Xin Zhao","doi":"10.1038/s41398-026-04345-3","DOIUrl":"https://doi.org/10.1038/s41398-026-04345-3","url":null,"abstract":"<p><p>Inhibitory control deficits are consistently observed in both schizophrenia (SCZ) and major depressive disorder (MDD), yet whether these impairments reflect shared tansdiagnostic mechanisms or disorder-specific dysfunction remains poorly understood. We recruited N = 259 participants (n = 87 SCZ, n = 86 MDD, n = 86 healthy controls) who completed Stroop and Go/No-Go tasks assessing interference and response inhibition, respectively. Hierarchical drift-diffusion modeling (HDDM) was used to decompose behavioral performance into latent computational parameters. Both patient groups exhibited significant behavioral impairments across most measures, with SCZ showing greater severity. At the computational level, reduced drift rate-reflecting less efficient evidence accumulation-emerged as a core transdiagnostic deficit across both inhibitory subcomponents and both disorders, with more pronounced reductions in SCZ. By contrast, prolonged non-decision time was disorder-differentiating, being consistently elevated across both tasks in SCZ but, in MDD, confined to response inhibition and not robust to processing-speed adjustment. Within-group clinical correlates further diverged, relating to negative-symptom severity and illness duration in SCZ and to current depressive symptom severity in MDD, although these diagnosis-specific associations were not directly compared across disorders. Machine learning classification corroborated these findings, with drift rate serving as the primary shared contributor to patient-control discrimination (area under the receiver operating characteristic curve [AUC] = 0.762-0.846), and non-decision time on the interference task the top-ranked feature in the SCZ-MDD classifier (AUC = 0.718). Together, these findings delineate shared versus disorder-specific computational signatures of inhibitory control impairment in SCZ and MDD, and suggest that computational phenotyping of inhibitory control may serve as a quantitative adjunct in precision psychiatry. Preregistration: This study was preregistered with the Chinese Clinical Trial Registry prior to data collection (registration number: ChiCTR2500111117; https://www.chictr.org.cn/showproj.html?proj=290089 ).</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149288833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer's disease.","authors":"Junfang Zhang, Lipeng Sun, Xinyuan Yang, Lin Kang, Yingting Zheng, Qi Huang, Wei Xu, Yihui Guan, Jun Liu, Yulei Deng, Fang Xie, Xiaomeng Xu, Binyin Li","doi":"10.1038/s41398-026-04292-z","DOIUrl":"10.1038/s41398-026-04292-z","url":null,"abstract":"<p><p>White matter microstructural changes play a crucial role in cognitive decline in aging and neurodegenerative disorders including Alzheimer's disease (AD). However, the processes underlying white matter microstructural changes and the molecular pathways leading to these changes in AD remain largely unknown. AD involves cortical and juxtacortical microstructural changes, with free water fraction (FWF) as a potential imaging marker. We measured FWF using diffusion magnetic resonance imaging in 68 juxtacortical regions of 153 cognitively normal controls and 194 patients with AD as evidenced by elevated amyloid PET. We estimated the expression of 15,633 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. The biological processes and cell types associated with the linked genes were evaluated. Mediation analysis was used to examine whether FWF mediates the association between APOE ε4 status and cognitive performance. Gene ontological analyses revealed that these genes were enriched for biological processes relating to lipid metabolic process, ensheathment of neurons, and synaptic signaling and were predominantly expressed in oligodendrocytes, GABAergic neurons, and pyramidal neurons from the hippocampus CA region. These ontological enrichment results were replicated in two additional datasets. Furthermore, mediation analyses revealed a domain-specific role of FWF in the association between APOE ε4 status and cognitive performance. Our findings provide mechanistic insights into regional juxtacortical microstructural changes in AD, particularly the processes involving lipid metabolism, offering potential therapeutic targets.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978030","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":"Deep brain stimulation ameliorates social deficits from early-life pain by restoring excitatory/inhibitory balance in the anterior cingulate cortex.","authors":"Xiangdong Wan, Tao Du, Dou Yang, Zaiying Jiang, Xiangyu Zhang, Yunjian Huang, Siyi Liu, Shiyun Xu, He Zhang, Guang Lu, Bing Ni, Hongwei Zhu","doi":"10.1038/s41398-026-04311-z","DOIUrl":"10.1038/s41398-026-04311-z","url":null,"abstract":"<p><p>The neural mechanisms underlying how early-life pain leads to long-term impairments in adult social deficit remain largely elusive. Here, by establishing a juvenile inflammatory pain model in mice and employing a combination of neuromodulation techniques, we found that early-life pain experience induces a specific and enduring social deficit in adulthood. This deficit originates from a persistent excitatory/inhibitory (E/I) imbalance within the anterior cingulate cortex (ACC). Specifically, during social interaction, we observed diminished activity in ACC excitatory neurons alongside hyperfunction of inhibitory GABAergic neurons, resulting in insufficient synaptic glutamate release. Targeted metabolomics analysis further confirmed aberrant levels of glutamate and GABA within the ACC. Targeting this mechanism, we demonstrated that either enhancing ACC excitation or dampening its inhibition via optogenetic and chemogenetic manipulations effectively rescued the social deficit. Importantly, deep brain stimulation (DBS) targeting the ACC also activated excitatory neurons and successfully reversed this social deficit. This study unveils a core mechanism whereby early-life pain impairs social function by inducing a state of hypoexcitation and hyperinhibition in the ACC. Furthermore, we establish that DBS can effectively rectify this ACC imbalance, providing a novel theoretical basis and a potential translational strategy for intervening in social deficits associated with developmental trauma.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13710537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273572","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":"Dual immune dysregulation in adolescent-onset schizophrenia: attenuated B cell trophic support and elevated IL-23/Th17 inflammation are diagnostic and clinical biomarkers.","authors":"Haidong Yang, Lingshu Luan, Yubing Han, Sijin Li, Man Yang, Xiaobin Zhang","doi":"10.1038/s41398-026-04343-5","DOIUrl":"10.1038/s41398-026-04343-5","url":null,"abstract":"<p><p>Adolescent-onset schizophrenia (AOS) is marked by severe symptoms and cognitive impairments, yet its peripheral immune profile remains insufficiently characterized. This cross-sectional study aimed to develop composite immune pathway indices integrating serum B cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), interleukin (IL)-23, and IL-17 levels to reflect immune dysfunction. We examined 93 patients with first-episode, antipsychotic-naive AOS and 40 healthy controls. Five indices were constructed: immune homeostasis protection index (IHPI), BAFF-APRIL immune ratio (BAIR), immune drive-attenuation ratio (IDA), Th17 decoupling index (TDI), and full immune imbalance index (FIII). Serum BAFF (t = -3.324, P = 0.001) and APRIL (t = -3.687, P < 0.001) were significantly reduced and IL-23 was increased (Z = -2.777, P = 0.005), whereas IL-17 remained unchanged (P = 0.292) in patients with AOS. BAIR did not differ between groups (P = 0.741). IHPI was significantly reduced in patients with AOS (t = -5.203, P < 0.001), whereas IDA, TDI, and FIII were elevated (all P < 0.001). Serum IL-23 was independently associated with Positive and Negative Syndrome Scale total score (β = 0.321, P = 0.002) and general psychopathology subscale score (β = 0.320, P = 0.001). In healthy controls, serum BAFF predicted immediate memory (β = 0.408, P = 0.009) and Repeatable Battery for the Assessment of Neuropsychological Status total score (β = 0.444, P = 0.005), an association not observed in patients with AOS. Among composite indices, IHPI achieved the best discriminative performance (AUC = 0.751, sensitivity: 69.9%, and specificity: 72.5%), outperforming individual biomarkers. These findings indicated that dual peripheral immune dysregulation in AOS was characterized by attenuated B cell trophic support and upstream IL-23/Th17 activation, and suggested that composite immune indices may provide incremental diagnostic value over single cytokines.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13710852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273530","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":"Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients.","authors":"Hannah Hacker, Linnea Hoheisel, Madalina-Octavia Buciuman, Annkathrin Böke, Theresa Lichtenstein, Marlene Rosen, Shalaila S Haas, Anne Ruef, Dominic B Dwyer, Paolo Brambilla, Carolina Bonivento, Rachel Upthegrove, Stephen J Wood, Stefan Borgwardt, Eva Meisenzahl, Stephan Ruhrmann, Raimo K R Salokangas, Alessandro Bertolino, Rebekka Lencer, Udo Dannlowski, Nikolaos Koutsouleris, Lana Kambeitz-Ilankovic, Joseph Kambeitz","doi":"10.1038/s41398-026-04206-z","DOIUrl":"10.1038/s41398-026-04206-z","url":null,"abstract":"<p><p>Individuals with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory and higher-order brain regions. In this study, we investigate disruptions in the hierarchical organization of brain functional networks in individuals with psychotic and affective disorders. We derived functional brain gradients, low dimensional representations of rs-FC that capture cortical hierarchy, in a sample of 1071 (56.3% female) participants, including clinical high-risk for psychosis (CHR-P) individuals, recent-onset psychosis (ROP) patients, recent-onset depression (ROD) patients, and healthy controls (HC). We examined regional alterations, network-level alterations and functional differentiation and their relationship to clinical symptoms. In addition, we linked case-control differences to receptor expression maps to explore underlying neurobiological mechanisms. All clinical groups exhibited alterations in the visual-to-sensorimotor gradient, while only ROP patients showed alterations in the sensory-to-association gradient. CHR-P and ROP individuals exhibited lower values in the ventral attention network. Clinical groups combined showed higher values in the somatomotor network, a reduced gradient range and altered between-network dispersion. ROD patients showed reduced within-network dispersion in the attentional networks and a reduced range. Correlational analysis revealed weak associations of gradient measures with functioning, visual dysfunctions and cognition. Case-control differences showed associations to receptor expression maps, suggesting the involvement of neurotransmitter systems in these disruptions. Our findings reveal transdiagnostic and disease-specific alterations of hierarchical brain organization. These alterations indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621487","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}