Background:Psychotic disorder represents a leading cause of disability worldwide, and relapse in psychosis is common. Artificial intelligence (AI) is increasingly recognized as a method that could aid clinical monitoring for individuals experiencing psychosis. Objective:This review aims to map the existing literature on AI-based approaches-including machine learning, deep learning, and natural language processing-used to detect relapse in individuals with psychotic disorders. Methods:A systematic search strategy was conducted on PubMed, PsycINFO, and Embase up to January 7, 2026. Observational studies, randomized controlled trials, and quasi-experimental studies that used AI methods to detect relapse in psychosis were eligible for inclusion. Screening and data extraction procedures were conducted by at least 2 reviewers working independently. Findings were extracted, charted, and described using narrative synthesis based on data extraction and consensus meetings with the research team. The scoping review was prospectively registered with the Open Science Framework. Results:Relevant studies identified (N=10) included the use of digital tools such as smartphone- and smartwatch-based monitoring, ecological momentary assessment tools, social media activity, and internet searches. Digital phenotyping via smartphones and wearables emerged as the most common method for data collection. The efficacy of AI models varied with sensitivity (or recall) ranging from 0.25 to 0.77 and specificity (or precision) ranging from 0.06 to 0.88. The reported area under the receiver operating characteristic curve for models ranged from 0.63 to 0.78. AI models were heterogeneous across studies, and most study findings were not replicated. Conclusions:This scoping review highlights both the promise and the current limitations of AI in psychosis relapse detection. Passive digital phenotyping research in the detection of psychosis relapse has progressed, and personalized approaches with individual-level modeling show promise; however, further studies need to include larger numbers of participants and should incorporate methods such as large language models. Future studies will require large collaborations aimed at delivering AI methods for use in real-world clinical practice.

Background Social cognition (SC) is central to functioning in schizophrenia spectrum disorders, yet most studies examine single disease stages or domains. It therefore remains unclear whether five SC domains (Theory of Mind [ToM], Social Perception [SP], Social Knowledge [SK], Emotion Recognition [ER], Attributional Bias [AB]) show homogenous impairments and follow a stage-like patterns across the psychosis spectrum. Methods A total of 359 participants (schizophrenia [SCH] = 59; first-episode psychosis [FEP] = 75; ultra-high risk [UHR-P] = 84; familial high-risk [FHR-P] = 55; healthy controls = 86) were administered a comprehensive SC battery and clinical scales. Group differences and linear trends (stage-ordered differences; stepwise gradients from FHR-P to SCH) were analyzed by ANCOVAs controlling for age and education. Associations with clinical variables were assessed using Spearman correlation. Results ANCOVA revealed a significant group difference only in ToM domain (p = .025), with lower performance in patients compared to asymptomatic FHRP. Linear trend analysis indicated small, but significant staging pattern in ToM (p = .023) and SK (p = .015). No significant staging was observed in SP, ER or AB. Better ToM and SK performance correlated with better functioning, fewer negative symptoms, and later age of onset. Conclusions SC impairment in psychosis is heterogeneous. ToM, and to a lesser extent SK, shows stage-ordered differences and significant clinical links, whereas SP, ER, and AB exhibit relatively flatter stage profiles across the psychosis spectrum. Given the cross-sectional design and modest effect sizes, conclusions about within-person change are not warranted.

BACKGROUND:Cognitive deficits are cardinal features of schizophrenia-spectrum disorders (SSD) and bipolar disorder (BD). However, their heterogeneous and overlapping characteristics require a dimensional approach to better understand the neurobiological basis of cognition in the psychosis spectrum. To date, only a few studies have examined the neuroanatomical features of cognitive subgroups in transdiagnostic samples, and white matter microstructural characteristics of these subgroups have not been elucidated. This study aimed to investigate white matter and cortical thickness alterations in cognitive subgroups in the schizophrenia-bipolar spectrum. METHODS:Globally Impaired (n = 31) and Near-Normal (n = 28) cognitive subgroups, comprising individuals diagnosed with schizophrenia (SZ), schizoaffective disorder (SAD) or BD, and healthy controls (HCs, n = 29), underwent 3T T1-weighted structural magnetic resonance imaging and diffusion tensor imaging scanning. Fractional anisotropy and cortical thickness measures were compared between the cognitive subgroups and healthy controls. RESULTS:Abnormalities in white matter microstructure were only observed in patients with global cognitive impairment compared to HCs. The Near-Normal subgroup did not differ from HCs in white matter integrity. A bilateral reduction in cortical thickness was observed in both the Globally Impaired and Near-Normal subgroups when compared to HCs. Cortical thickness measures did not differentiate between the cognitive subgroups. CONCLUSIONS:While reductions in cortical thickness in frontal and temporal regions appear to be a common feature of SZ and BD, abnormalities in white matter microstructure are associated with global cognitive impairment in the schizophrenia-bipolar spectrum. These original findings may be important in identifying more biologically valid clinical syndromes within the schizophrenia-bipolar spectrum.

Chorea-acanthocytosis is one of the neuroacanthocytosis syndromes; a rare (1-5 per 1,000,000) and progressive neurodegenerative disorder characterized by abnormalities in the nervous system accompanied by erythrocyte acanthocytosis. Various neurological dysfunctions and psychiatric symptoms coexist, significantly reducing both quality of life and life expectancy. Due to the rarity of the disease, diagnosis can sometimes be delayed; the initial presentation may include vague cognitive or psychiatric symptoms, leading to prolonged misdiagnoses and incorrect management. In middle-aged adults presenting with chorea and tic-like involuntary movements alongside psychiatric disorders, neuroacanthocytosis syndromes should always be considered. A thorough neurological and psychiatric examination should be conducted, and necessary imaging and laboratory tests should be performed.In this case report, we present the detailed diagnostic evaluation process of a patient suspected of having chorea-acanthocytosis with neuropsychiatric symptoms, in light of the existing literature.

Impairments in thought, language and communication in schizophrenia spectrum disorder (SSD) were conceptualized as formal thought disorder (FTD). In particular, disturbances of the thinking processes may be reflected by semantic incoherence and semantic perseveration in discourse dynamics in the speech of SSD. Recent advancements in natural language processing offer a way to evaluate these semantic impairments objectively by computing semantic similarity between consecutive language units. In this regard, investigating the neuroanatomical substrates of semantic similarity is an important next step. In this study, we collected speech samples from a total of 98 subjects, 64 patients with SSD and 34 healthy control subjects using a semi-structured free speech task. The semantic similarity analysis comprised the mean, variance, 5th percentile and 95th percentile of similarity values between consecutive words. We investigated the neural correlates of semantic similarity using voxel-based morphometry and surface-based morphometry, including cortical thickness, gyrification, sulcal depth and fractal dimension. The correlation analysis resulted in an association of a decrease in the lowest semantic similarities of neighboring words with a decrease in cortical thickness, not only in traditional language processing regions but also extending to bilateral frontal, temporal and parietal regions. The strongest associations were found with bilateral superior frontal and rostral middle frontal regions. We also found a negative association between the lowest semantic similarities and fractal dimension in the left superior frontal region. Altogether, our findings indicate the more integrative proposals that link semantic similarity and FTD with neurocognitive processes. These outcomes suggest that semantic similarity may not solely be an indicator of impairments in language production, but rather disruptions in higher cognitive processes in schizophrenia.

BACKGROUND AND HYPOTHESIS:Abnormalities in the retina are observed in psychotic disorders, especially in schizophrenia. STUDY DESIGN:Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28). STUDY RESULTS:Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen's d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = -0.75/-0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70-1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64-1.01). In the macula, while central sector thickness/volume decreased (d = -0.62 to -0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs. CONCLUSIONS:The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels.

INTRODUCTION:The course of psychotic disorders typically involves relapses. Early warning signs vary between individuals and are difficult to detect in clinical practice, especially in outpatient settings. Speech provides a quantitative clinical marker for detecting such early warning signs. The EU Horizon project TRUSTING (A TRUSTworthy speech-based AI monitoring system for the prediction of relapse in individuals with schizophrenia) aims to develop and evaluate a speech-based monitoring system for predicting imminent psychotic relapses. The study will examine the potential for prospective relapse prediction, and feasibility and usability of the monitoring system. METHODS AND ANALYSIS:In this multicentre observational study, n=240 remitted and at-risk-of-relapse adults with psychotic disorders and a comparison group with n=120 healthy participants (matched by age and sex) will be examined at six sites and in six different languages (German, French, Dutch, English, Czech and Turkish). The follow-up period is 6 months. The TRUSTING smartphone app will be used to collect weekly voice recordings through speech tasks; information on medication adherence, substance use, mood, anxiety and sleep quality; and motor data from a tapping task. Primary endpoints encompass model performance for relapse prediction, user adherence, transcription quality, usability of recordings and overall system usability. The primary analysis of user adherence, transcription quality, usability of recordings and overall system usability will be an unadjusted description of the respective proportions using 95% Wilson confidence intervals. Regarding relapse prediction, the predictive value of the risk estimates for relapse occurrence will be assessed using the area under the receiver operating characteristic curve. Exploratory analysis will be performed on potential speech-based markers associated with relapse risk. ETHICS AND DISSEMINATION:This study has been approved by swissethics (Business Administration System for Ethics Committees number: 2025-01177). Findings from this project will be disseminated through peer-reviewed journal publications and presentations at relevant scientific conferences, as well as at public events related to mental health. TRIAL REGISTRATION:ClinicalTrials.gov ID: NCT07397975.

Neuroimaging studies in familial high-risk (FHR) individuals are vital for identifying vulnerability markers independent of overt illness. However, research on purely non-prodromal FHR cohorts using comparative multimodal approaches remains limited. This study addresses this gap through multimodal MRI analysis-including cortical morphometry, white matter microstructure, tractography, and functional connectivity-in non-prodromal FHR for psychosis (FHR-P, n = 18), bipolar disorder (FHR-BD, n = 19), and healthy controls (HC, n = 25). FHR-BD showed increased right inferior parietal surface area and right middle temporal volume compared to HC. Conversely, FHR-P exhibited reduced right superior frontal cortical thickness compared to FHR-BD and decreased left pallidum volume compared to HC. White matter analysis revealed significantly lower fractional anisotropy in FHR-P compared to both FHR-BD and HC. FHR-BD showed higher axial diffusivity than HC in the forceps minor, uncinate fasciculus, and right-fronto-occipital fasciculus. No significant differences were found in network-based statistics or graph theoretical measures. These findings reveal shared and distinct neurobiological alterations in non-prodromal FHR-P and FHR-BD, suggesting that grey and white matter disruptions constitute endophenotypes even without clinical symptoms. The lack of network-level findings may reflect the modest sample size, requiring further investigation in larger cohorts.

OBJECTIVE:The study aims to examine the relationship between subjective cognitive complaints (SCC) and objective cognitive performance (OCP) in severe mental disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). METHOD:Systematic literature searches were conducted using Web of Science and PubMed, including articles published until September 2025. Studies were included if they assessed both SCC and OCP using validated instruments in individuals diagnosed with SCZ, BD, or MDD and were peer-reviewed English research articles. A series of meta-analyses was conducted using random-effects models to examine the associations between SCC and composite OCP scores, as well as the subdomains of objective cognition. Analyses were repeated for each diagnosis. RESULTS:The sample included 49 articles with 5,007 participants. Our analyses yielded a small but statistically significant correlation between SCC and global OCP (r = -0.145). Domain-wise associations indicated correlations between SCC and OCPs in processing speed, attention/vigilance, working memory, and verbal learning/memory (correlation coefficients ranged from -0.107 to -0.172). In diagnosis-specific analyses, individuals with SCZ showed significant associations in all domains except executive function. In contrast, the associations were restricted to only a few cognitive domains in other disorders, specifically processing speed and working memory in BD, and processing speed and attention/vigilance in MDD. CONCLUSIONS:Although significant, the strength of these associations was small, suggesting that SCC explains only a limited proportion of the variance in OCP. This suggests that while SCC cannot substitute for objective testing, it provides complementary information that reflects patients' experiences of cognitive dysfunction.

OBJECTIVE:This study aimed to adapt the Movie for the Assessment of Social Cognition (MASC) into Turkish (MASC-TR), examine its psychometric properties, and establish normative data. Additionally, the study investigated the discriminative validity of the MASC-TR in differentiating individuals with autism spectrum disorder (ASD) from healthy controls. METHODS:The sample comprised 228 healthy adults and 29 individuals with ASD aged 18-45 years. Participants completed the MASC-TR along with established measures of theory of mind (ToM)-the Reading the Mind in the Eyes Test (RMET) and the Faux Pas Recognition Test (FPRT)-as well as non-social cognitive tasks assessing attention, working memory, and executive functions. Reliability analyses included internal consistency and test-retest reliability. Construct validity was assessed via convergent and discriminant correlations. Group comparisons and receiver operating characteristic analyses were used to evaluate discriminative validity, while multifactorial analysis of variance and regression analyses examined demographic effects. RESULTS:The MASC-TR demonstrated acceptable internal consistency (α = 0.75) and excellent test-retest reliability (ICC = 0.98). Significant positive correlations with RMET and FPRT supported convergent validity. Education level emerged as the only significant demographic predictor of MASC-TR performance. The MASC-TR successfully differentiated individuals with ASD from controls (t = -3.87, p < .001), with an optimal cutoff of 23.5 yielding 97% sensitivity and 52% specificity (area under the curve = 0.72). CONCLUSIONS:The findings indicate that the MASC-TR is a valid and reliable measure of social cognition in Turkish adults. The availability of culturally adapted normative data enhances its clinical and research utility for assessing ToM functioning across populations.

AIM:Jumping to conclusions (JTC) bias, which is frequently observed in psychosis, is the tendency to make decisions based on inadequate information. This study explored JTC bias in individuals with first-episode bipolar disorder (FEBD, n = 52), first-episode psychosis (FEP, n = 61) and healthy controls (HCs, n = 38). METHOD:JTC bias was assessed using the Bead Task, in which participants were asked to draw as many beads as they wanted and make conclusions about their source. RESULT:The results showed that both the FEBD and FEP groups exhibited a significantly longer response time and higher tendency to make decisions after drawing a single bead compared to HCs, indicating a subtle tendency towards hastier decision-making in these patient groups. No significant correlations were found between JTC bias and clinical measures. DISCUSSION:This study highlights that JTC bias is present in both FEP and FEBD, pointing to potential vulnerabilities in decision-making early in these disorders. These findings highlight the need for further research to determine whether addressing reasoning biases could ultimately benefit decision-making processes in these populations.

The notion of pink noise refers to 'scale-invariant' temporal dynamics, where fluctuations exhibit similar statistical structure across time scales. Departures from a regime associated with such scale-free organization toward uncorrelated 'white' noise or overly persistent 'brown' noise have been widely identified as markers of pathology across physiological and cognitive domains. Whether comparable alterations characterize the temporal organization of language remains largely unexplored. We address this question in the domain of psychosis, where language anomalies are pervasively documented. Specifically, we apply detrended fluctuation analysis (DFA) to quantify temporal scaling in BERT-derived continuous cosine-similarity time series capturing trajectories through semantic space, using clinical transcripts from patients and controls across three independent datasets. DFA scaling exponents were extracted to characterize the strength of long-range temporal correlations. Across all datasets, patients exhibited significantly elevated scaling exponents relative to controls, indicating abnormally strong long-range correlations with excessive persistence in semantic fluctuations. This temporal analysis opens a window into the multi-timescale organization of meaning as it unfolds in discourse. The results reveal a signature of altered temporal scaling in speech, consistent with deviations from criticality in physiological domains, paralleling known departures from criticality in brain function in psychosis and suggesting possible links between these two domains.

Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Objectives: This study aimed to compare social cognition and apathy between patients with amyotrophic lateral sclerosis (ALS) without dementia and healthy controls (HCs). Patients and methods: This cross-sectional study examined 17 patients (9 males, 8 females; median age: 58 years; range, 31 to 70 years) with ALS and 34 HCs (19 males, 15 females; median age: 58.5 years; range, 31 to 69 years) between February 2024 and February 2025. Data from the Beck Depression Inventory, the revised ALS Functional Rating Scale, reading the mind in the eyes test, and theory of mind (ToM) tests were collected. The results were compared with HCs. Results: There were no significant differences between groups in terms of age, education level, or sex ( p > 0.05). Affective ToM scores were comparable between groups ( p > 0.05). Patients with ALS exhibited lower median cognitive ToM scores than HCs (27 [7.5] vs. 30 [5], p = 0.035). The median total Dimensional Apathy Scale scores were higher in the ALS group than in the HC group (18 [11.5] vs. 12 [5.25], p = 0.001). The groups differed in the cognitive and emotional dimensions of apathy but not in the executive dimension. Conclusion: Lower cognitive ToM performance, higher initiation, and emotional apathy scores were observed at increased rates in patients with ALS without dementia.

Background speech carries cues to variation in mental state in schizophrenia spectrum disorders/psychotic disorders, typically indexed with clinician-rated scales such as the PANSS. Progress in the automation of speech- based symptom modelling has been constrained by data scale and the underrepresentation of low-resource languages. In this study, we aggregate multi-center recordings to assemble a large corpus and assess symptom-prediction models at scale, to enable more objective and efficient assessments and the early detection of relapse-related signals from speech. Methods We compiled data from 453 patients with schizophrenia spectrum disorders, recruited from ten global sites, and clipped their speech recordings into 6,664 segments. Across three feature sets, acoustic-prosodic profile, pretrained multilingual embeddings, and their concatenation, we compared 16 algorithms to predict eight relapse-related PANSS items, including three positive (P1, P2, P3), three negative (N1, N4, N6), and two general (G5, G9) items, on speaker-disjoint splits (80% train, 10% test, and 10% validation). Performance was assessed by root-mean-squared-error (RMSE) at both segment and participant (median aggregation) levels. Best model per item underwent bias checks for age, sex, education, and symptom severity. Outcomes Best-performing models predicted symptoms with prediction errors of 1.5 PANSS points or lower: P1 1.494/1.527, P2 1.318/1.107, P3 1.407/1.542, N1 1.029/1.030, N4 1.452/1.430, N6 0.860/0.855, G5 0.850/0.882, G9 1.213/1.282 (segment/participant). Performance of the pretrained multilingual embeddings surpassed acoustic-prosodic features and their concatenation. Results were comparable in low-resource languages (e.g., Czech). We found no bias by age, sex, or education, aside from reduced N4 accuracy in males; but performance degraded with higher symptom severity. Interpretation Speech can support automatic assessment of schizophrenia symptoms using pretrained multilingual embeddings, even without the use of transcripts. Such models show promise as clinically meaningful, efficient, and low-burden tools for real-time monitoring of symptom trajectories. Funding EU Horizon research and innovation programme. ### Competing Interest Statement LP reports personal fees for serving as chief editor from the Canadian Medical Association Journals, speaker/consultant fee from Janssen Canada and Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work. IS reports charity grant fro Janssen, speaker fee from Otzuka and Ludbeck. All other authors report no relevant conflicts. SXT owns equity and serves on the board and as a consultant for North Shore Therapeutics, received research funding and serves as a consultant for Winterlight Labs, is on the advisory board and owns equity for Psyrin, and serves as a consultant for Catholic Charities Neighborhood Services and LB Pharmaceuticals. PH has received grants and honoraria from Novartis, Lundbeck, Takeda, Mepha, Janssen, Boehringer Ingelheim, Neurolite and OM Pharma outside of this work. All other authors reported no conflict of interests. ### Funding Statement This work is part of the project "TRUSTworthy speech-based AI monitorING system for the prediction of relapse in individuals with schizophrenia (TRUSTING)", funded by the European Union Horizon Europe research and innovation programme under grant agreement No. 101080251. The views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them. Authors are listed in alphabetical order, except for local members of the leading research group and the TRUSTING Pis. Additional funders for data collection are as follows. English data: Brain and Behavior Research Foundation Young Investigator Grant (K23 MH130750, to SXT). Spanish data: Carlos III Health Institute (PI14/00639, PI14/00918, PI17/00221, PI20/00066, and PI23/00076, to RAA). Chilean Spanish data: National Agency for Research and Development (ANID), Chile (Fondecyt Regular Grant No. 1241618, to AFB). Swiss German data: Swiss National Science Foundation (Grant No. 191938, to PH), Brain and Behavior Research Foundation (Grant No. 28997, to PH), and OPO Foundation (Grant No. 2020-0075, to PH). Dutch data: RAPSODI study funded by ZonMW, Netherlands (Grant No. 80-83600-98-40120), as part of the research program Rational Pharmacotherapy (Goed Gebruik Geneesmiddelen) (Grant No. 836041008, to IS), and the HAMLETT study funded by ZonMW, Netherlands (Grant No. 80-84800-98-41015, to IS). Turkish data: Scientific and Technological Research Council of Turkey (TUBITAK 2247, Project No. 120C141). In addition, RAA was funded by a Miguel Servet contract from the Carlos III Health Institute (Grant No. CP18/00003) and a Consolidator Grant from the Ministerio de Ciencia e Innovacion (Grant No. CNS2022-136110). A.P. was supported by a Marie Sklodowska-Curie Actions H2020 MSCA IF 2018 grant (ID: 832518, Project: MOVES). A.S. was supported by the Carlsberg Foundation. KK was supported by the Japan Society for the Promotion of Science (JSPS). RHe was funded by the China Scholarship Council (Grant No. 202108390062) during part of this work and is currently funded by the DELTA-Lang project (Synergy Grant 2023, Grant No. 101118756). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics commission of National Institute of Mental Health (NIMH) of the Czech Republic. IRB at Feinstein Institutes for Medical Research, Northwell Health. Local Institutional Board at Valdecilla Research Institute (IDIVAL) in Santander, Spain. Review board (Ethics Committee for Clinical Research, CEC SSMS of Santiago, Chile). Ethical commission of the Department of Psychiatry in Montperrin Hospital, CH Aix-en-Provence, France. Ethics committee of Kantonale Ethikkommission Zurich. Review boards of the University medical center Utrecht and Groningen. Ethics Committee of Dokuz Eylul University. Ethics Committee of the State Chamber of Physicians Westphalia-Lippe and the University of Muenster. Ethics committee of Renmin Hospital of Wuhan University and the Institutional Review Board of the Institute of Psychology, the Chinese Academy of Sciences. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The original data cannot be publicly shared due to ethical restrictions. However, all scripts and results will soon be available at https://github.com/RuiHe1999/PANSS_prediction.

BACKGROUND AND HYPOTHESIS:Cognitive deficits are central to schizophrenia-spectrum disorders and already present in many patients at first-episode psychosis (FEP). Prior meta-analyses suggest cognitive deficits remain relatively stable, but most of them tracked patients for only a few years and rarely compared trajectories directly with matched healthy controls (HCs). We aimed to characterize cognitive trajectories over long-term follow-ups. STUDY DESIGN:Following PRISMA-2020 guidelines, we searched databases for longitudinal studies of cognition in recent-onset psychosis. Forty-nine datasets (3693 FEP and 1399 HCs) were included, with follow-ups ranging from 2 to 25 years. Random-effects meta-analyses quantified within-group change (FEP and HC separately) and between-group differences (FEP-vs.-HC) across short (2-5 years), mid (5-10 years), and long-term (≥10 years) intervals. Meta-regressions examined the influence of clinical moderators. STUDY RESULTS:Both FEP patients and HCs showed either stable performance or small effect-size improvements in global (FEP: d = 0.22, P < .0001) and domain-specific cognition over long-term, with no evidence of progressive deterioration. Direct comparisons revealed no FEP-vs.-HC differences in global cognitive change overall (d = 0.05, P = .568) or within any follow-up interval (short, mid, and long). Across domains, the only exception was attention, where patients improved compared to controls. Changes in positive and negative symptoms were unrelated to changes in global cognition. CONCLUSIONS:Neuropsychological performance in FEP remains stable for at least a decade, with modest gains largely attributable to practice effects and no sign of neurodegenerative decline. These trait-like deficits appear partly independent of long-term symptom changes, and further support neurodevelopmental over neurodegenerative models of schizophrenia.

BACKGROUND:Minor physical anomalies (MPAs) are subtle morphological variants that may reflect atypical prenatal development. Elevated MPAs have been reported in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but findings have been inconsistent. METHODS:We systematically searched PubMed, Web of Science, and grey-literature sources for case-control studies published through December 2025 that reported total MPA scores in ASD or ADHD versus typically developing controls. Pooled effect sizes were calculated as Hedges' g using random-effects models with restricted maximum likelihood estimation. Shared control groups were handled by sample splitting. Heterogeneity, subgroup and moderator effects, and small-study effects were examined. RESULTS:Twelve ASD studies and eight ADHD studies met inclusion criteria. Across disorders, MPAs were significantly elevated relative to controls (pooled g = 0.72, 95% CI 0.56-0.89). Disorder-specific pooled estimates were significant for both ASD (g = 0.69) and ADHD (g = 0.77), with no significant difference between disorders (Qbet = 0.22, p = 0.64). In ASD, effects were stronger for craniofacial anomalies than for peripheral anomalies, and item-level syntheses highlighted several ear- and palate-related features. In ADHD, evidence of small-study effects suggested possible overestimation, although conclusions remained robust in sensitivity analyses. CONCLUSIONS:MPAs are reliably elevated in both ASD and ADHD. Current case-control evidence supports MPAs as a transdiagnostic marker of early developmental perturbation rather than a feature that strongly differentiates between these disorders.

Computational linguistic analysis has been increasingly used to capture formal thought disorder in schizophrenia. Despite promising outcomes, investigations of the computational linguistic disturbances of schizophrenia in a transdiagnostic context are limited. Particularly, shared characteristics, neurodevelopmental origins, and the role of speech in the diagnosis of schizophrenia and autism indicate a need to explore both the commonalities and distinctions in the computational linguistic profiles of these groups. In this study, we investigated the semantic and structural properties of speech samples of 35 patients with schizophrenia spectrum disorder, 25 patients with autism spectrum disorder, and 25 healthy controls in free speech and picture description tasks. Our findings showed that only 5 of 45 features differed between the clinical groups. All of these were from the structural domain, while semantic features did not differ between these neurodevelopmental disorders. The clinical groups demonstrated elevated local and global semantic similarity, and negative sentiment compared to controls. Moreover, the speech of autism spectrum disorder included lower unique word frequency in picture description, alongside shorter pronouns and adverbs in free speech relative to other groups. Schizophrenia spectrum disorder used shorter adjectives than autism spectrum disorder and controls in free speech. Importantly, adjective frequency in schizophrenia spectrum disorder was lower than in autism spectrum disorder in free speech. Overall, our findings demonstrated an extensive dominance of similar computational linguistic traits between schizophrenia and autism spectrum disorders, indicating shared communication disturbances in these disorders. This outcome highlights the critical role of transdiagnostic and neurodevelopmental perspectives in computational linguistic investigations.

BACKGROUND:Socio-cognitive assessment in neurocognitive disorders (NCDs) is rare in clinical practice and no consensus exists as to a uniform operationalization of socio-cognitive measures for NCDs in memory clinics. The SIGNATURE initiative aims to optimize the use of socio-cognitive measures in memory clinics, defining expert recommendations. We report consortium guidelines for the use of socio-cognitive measures in NCDs based on available evidence from the literature and the current state of practices in memory clinics. METHODS:Using a Delphi consensus method supported by a literature review and the results of an international survey, 22 specialists defined recommendations for the context of use, relevance in NCD diagnosis, priorities for future research and facilitators/obstacles of socio-cognitive assessment in major and mild NCDs. RESULTS:Overall, panelists recommended social cognition testing in routine diagnostic assessment to evaluate both socio-cognitive and socio-behavioral alterations. A set of clinical, methodological, implementation and external factors facilitating or hampering the use of socio-cognitive tasks was identified. CONCLUSIONS:This is the first focused endeavor to favor the implementation of socio-cognitive assessment, which is required by DSM-5 but seldom performed despite clear evidence of its clinical relevance for diagnosis and care. Our results provide an initial set of recommendations, refinable through the future actions of the SIGNATURE initiative. Future collaborative clinical research projects should overcome current limitations and foster the use of ecological and cross-culturally validated measures in clinics.

Background: Recent research has suggested that bipolar disorder (BD) might be associated with accelerated aging. Multiple studies have shown telomere shortening in BD but others did not support this notion. In BD, TL can be influenced by factors such as aging, smoking, metabolic syndrome, the nature of the disorder, and lithium use. To evaluate differences in TL between individuals with BD and healthy controls and to explore potential factors influencing telomere shortening, we conducted a meta-analysis of studies comparing these populations. Methods: A systematic literature search was conducted in PubMed and Scopus databases up to November 2024. Original research articles reporting TL measures were selected. Results: A total of 24 studies, including 2330 patients diagnosed with BD and 2912 healthy controls, were included in the analysis. TL was significantly shorter in patients with BD compared to controls (Hedges' g, -0.42; 95% CI, -0.6 to -0.21; p <0.001). Meta-regression analyses showed that between-group differences in body mass index (BMI) had a significant effect on effect size. No statistically significant differences were found in subgroup analyses according to lithium use, duration of illness, telomere measurement method, substance use exclusion criteria, study quality, and euthymia. A moderate negative correlation was observed between age and TL in both BD and control groups ( r=-0.38, r=-0.37). Conclusion: Our results support the presence of illness-associated cellular aging in BD. Longitudinal studies with repeated TL measurements are needed to examine the potential effects of disease course, aging, illness duration, and medication on this process.