Nader G, Raymond R, Trad R
… +5 more, Ducharme M, Graff A, Gerretsen P, Fischer C, De Luca V
Schizophr Res
· 2026 Aug · PMID 42127842
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Suicide is a leading cause of death among individuals with schizophrenia. Studies suggest that suicide attempters show increased DNA methylation and shorter telomere lengths, both linked to accelerated biological aging....Suicide is a leading cause of death among individuals with schizophrenia. Studies suggest that suicide attempters show increased DNA methylation and shorter telomere lengths, both linked to accelerated biological aging. Recently, DNA methylation has been used to estimate epigenetic aging and telomere length, the former of which serves as the most accurate measure of biological aging. In this study, we investigated whether patients with schizophrenia spectrum disorder (SSD) and a history of suicide attempts show greater biological aging than non-attempters. Epigenetic aging and telomere length were assessed in DNA samples extracted from white blood cells of 60 SSD patients using methylation-based epigenetic clocks. Suicide attempters showed higher epigenetic age acceleration (EAA) on the Hannum DNAm Age clock compared to non-attempters, although other clocks displayed similar trends. However, this was no longer significant after correcting for multiple comparisons (p = 0.0356, p = 0.2136). These findings suggest that accelerated epigenetic aging may be associated with suicide risk in schizophrenia. Finally, investigating the factors underlying this association would improve our understanding of suicidality and the ability to develop effective prevention measures.
Abplanalp SJ, Strauss GP, Bucci P
… +3 more, Mucci A, Pezzella P, Galderisi S
Schizophr Res
· 2026 Aug · PMID 42127841
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INTRODUCTION: Negative symptoms are a core feature of schizophrenia and severely impact functioning and quality of life. The five symptom domains (anhedonia, asociality, avolition, blunted affect, and alogia) have emerge...INTRODUCTION: Negative symptoms are a core feature of schizophrenia and severely impact functioning and quality of life. The five symptom domains (anhedonia, asociality, avolition, blunted affect, and alogia) have emerged as the preferred structure of negative symptoms; however, it is unclear whether these dimensions demonstrate measurement bias across sociodemographic variables. We used regularized moderated nonlinear factor analysis (MNLFA) to evaluate potential sociodemographic bias in the measurement of negative symptoms among individuals with schizophrenia. METHODS: The study included two samples of people with schizophrenia (total n = 1175). Negative symptoms were assessed with the Brief Negative Symptom Scale. Regularized MNLFA was conducted to assess whether the five-factors of negative symptoms showed measurement bias at the item and latent levels as a function of age, education level, and sex. RESULTS: At the item level, the asociality behavior item showed differential item functioning, such that older participants were more likely to endorse more severe deficits on this item after accounting for their latent level of asociality. In addition, those with higher education levels were more likely to endorse more severe deficits on the avolition internal experience item after accounting for their latent level of avolition. Measurement bias was also present across all five of the latent negative symptom variables. CONCLUSION: As negative symptoms increasingly serve as treatment targets and surrogate outcomes, ensuring unbiased measurement is essential for advancing clinical precision. The presence of measurement bias underscores the need for careful consideration of age, education, and sex when interpreting symptom scores in both research and clinical settings.
Li Y, Lu C, Zhang J
… +8 more, Yue K, Li Y, Liu N, Wang X, Zhang X, Xu G, Li S, Li J
Schizophr Res
· 2026 Aug · PMID 42116246
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BACKGROUND: Deficit schizophrenia (DS) is a distinct subtype characterized by persistent negative symptoms. Uric acid (UA), a major endogenous antioxidant, shows marked sex differences, but its associations with psychopa...BACKGROUND: Deficit schizophrenia (DS) is a distinct subtype characterized by persistent negative symptoms. Uric acid (UA), a major endogenous antioxidant, shows marked sex differences, but its associations with psychopathology and cognition in DS remain unclear. This study examined sex-specific associations of serum UA with clinical symptoms and cognition in DS. METHODS: A total of 76 DS patients (47 men, 46.23 ± 12.51 years; 29 women, 50.86 ± 10.51 years) and 210 non-deficit schizophrenia (NDS) patients (88 men, 46.56 ± 12.03 years; 122 women, 45.49 ± 12.35 years) were enrolled. Psychopathology and cognition were assessed using the Positive and Negative Syndrome Scale and the Repeatable Battery for the Assessment of Neuropsychological Status. Serum UA was measured by enzymatic colorimetric assay. Sex and diagnosis effects were examined using two-way analysis of variance. Pearson correlation and multivariable linear regression analyses were performed within sex- and diagnosis-defined subgroups. RESULTS: A showed a significant main effect of sex (F = 40.82, p < 0.001), with higher levels in men than women in both DS and NDS. Distinct sex-specific associations were observed only in DS: in men, higher UA levels were independently associated with more severe positive symptoms (β = 0.301, p = 0.040), whereas in women, higher UA levels were associated with better delayed memory (β = 0.421, p = 0.009) and RBANS total score (β = 0.465, p = 0.006). No significant associations were observed in NDS. CONCLUSIONS: Serum UA shows distinct sex-specific associations with symptom and cognitive profiles in DS.
Carroll D, Rintell LS, D'Angelo EJ
… +4 more, Lopez D, São-João TM, Gonzalez-Heydrich J, Arcoleo K
Schizophr Res
· 2026 Aug · PMID 42107176
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BACKGROUND: Caregiver burden is well characterized in adults with psychosis but less is known about the burden experienced by carers of children with psychosis. In this secondary analysis, we examined burden reported by...BACKGROUND: Caregiver burden is well characterized in adults with psychosis but less is known about the burden experienced by carers of children with psychosis. In this secondary analysis, we examined burden reported by caregivers of children with clinical high risk for psychosis and psychotic disorders to test an explanatory model for caregiver burden. METHODS: Cross-sectional analyses examined burden experienced by caregivers of children with clinical high risk for psychosis and psychosis who were recruited from an outpatient psychiatric clinic. Caregiver burden was assessed with the Zarit Burden Interview. Structural equation modeling was employed to examine a model assessing the simultaneous effects of factors related to burden among caregivers of children at clinical high risk for psychosis and diagnosed with psychotic disorders. RESULTS: The study involved 85 caregivers of children aged 6-17. The latent variable for positive caregiving attributes, which included parenting confidence and communication, had a direct effect on caregiver burden, with greater levels of positive caregiving attributes associated with decreased burden. Direct effects of social support and the latent variable for primary/secondary stressors on burden were not observed. There was a significant indirect effect for social support through positive caregiving attributes to mitigate the effects of primary/secondary stressors on caregiver burden. CONCLUSION: The results provide preliminary evidence supporting the importance of social support, parenting confidence, and caregiver-child communication as targets for intervention. Moreover, our findings suggest that despite stressors, such as suicidal behavior and psychiatric hospitalizations, modifiable factors exist that may serve as protective buffers against caregiver burden.
Lan M, Wang L, Wang B
… +4 more, Cao T, Wang Z, Wang K, He S
Schizophr Res
· 2026 Aug · PMID 42092306
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BACKGROUND: Visual perceptual functions are frequently disrupted in patients with schizophrenia. The nature and degree of the visual abnormalities experienced by patients provide important information about altered cogni...BACKGROUND: Visual perceptual functions are frequently disrupted in patients with schizophrenia. The nature and degree of the visual abnormalities experienced by patients provide important information about altered cognitive mechanisms and may serve as potential endophenotypes for classification and diagnosis of schizophrenia. METHODS: To characterize dynamic and integrative visual functions and distinguish patients with schizophrenia from healthy controls, we compared performance on six visual tasks between patients and healthy controls. The tasks included binocular rivalry (interocular dynamics), structure from motion (3D-surface dynamics), surround suppression of contrast (contextual modulation), contour integration (form integration), coherent motion (motion integration), and motion speed discrimination (motion sensitivity). The same set of tests was conducted in 61 early-stage outpatients and 69 chronic inpatients and controls, allowing us to see the effects of long-term treatment on patients' visual functions. RESULTS: Compared with healthy controls, patients experienced slower switching in binocular rivalry but faster switching in structure from motion, along with impaired spatial form integration. Inpatients had reduced motion sensitivity, while outpatients had deficits in motion integration, two groups differed in susceptibility to surround contrast suppression. Multidimensional test data supported more accurate classification between patients and controls. CONCLUSIONS: Patients with schizophrenia have specific patterns of visual perceptual abnormalities in dynamic and integrative information processing, with deficit in coherent motion (considered more state-linked) more apparent in early-stage outpatients and poor motion speed discrimination (linked to stable traits) seen in chronic inpatients. There is a significant advantage of using multiple independent tests to assist in the classification and diagnosis of schizophrenia.
Ryu S, Kim JW, Jhon M
… +5 more, Chung YC, Kim SJ, Lee S, Kim JM, Kim SW
Schizophr Res
· 2026 Aug · PMID 42092305
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BACKGROUND: Linguistic deficits are core features of schizophrenia. Perplexity (PPL) and pseudo-perplexity (PPPL), derived from language models, serve as probabilistic metrics of contextual uncertainty. This study invest...BACKGROUND: Linguistic deficits are core features of schizophrenia. Perplexity (PPL) and pseudo-perplexity (PPPL), derived from language models, serve as probabilistic metrics of contextual uncertainty. This study investigated their utility as objective markers for distinguishing patients with schizophrenia from healthy controls. METHODS: Speech samples were collected from 249 Korean-speaking patients with schizophrenia and 159 healthy controls across eight tasks, including free, emotional, and projective narratives. PPL and PPPL were calculated using autoregressive and bidirectional models, respectively. Group differences were assessed via Rank ANCOVA, adjusting for age, sex, education, and token count. Additionally, exploratory analyses examined correlations with clinical symptom severity. RESULTS: Patients exhibited significantly elevated PPL and PPPL values compared to controls across most tasks, a finding consistent across different model architectures. Exploratory correlation analyses indicated that both metrics were associated with global cognitive impairment (CGI-SCH Cognition) and difficulty in abstract thinking (PANSS N5), linking linguistic deviations to psychopathological severity. CONCLUSIONS: Elevated PPL and PPPL effectively characterize linguistic deviations in schizophrenia, reflecting heightened contextual uncertainty in language modeling associated with the underlying psychopathology. These findings support the utility of language models as automated, scalable tools for objectively quantifying linguistic pathology and elucidating the neurocognitive substrates of schizophrenia.
Schizophr Res
· 2026 Aug · PMID 42070513
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BACKGROUND: The negative symptoms of schizophrenia are strongly associated with functional disability and reduced quality of life yet remain among the least effectively treated symptoms. Existing pharmacological and psyc...BACKGROUND: The negative symptoms of schizophrenia are strongly associated with functional disability and reduced quality of life yet remain among the least effectively treated symptoms. Existing pharmacological and psychosocial recommendations show only modest empirical support and limited implementation in routine care. A growing number of psychosocial interventions have been developed to target specific mechanisms underlying negative symptoms, but the evidence base has not been mapped. METHODS: A scoping review was conducted following PRISMA guidelines to identify studies testing psychosocial interventions explicitly targeting negative symptoms or their theorised mechanisms in adults with a schizophrenia-spectrum diagnosis. Study characteristics, intervention targets and tools, and negative symptom outcomes were synthetised narratively. RESULTS: Thirty-one studies including RCTs (k = 18), pilot studies (k = 8), case series (k = 3), and other designs met the inclusion criteria. Interventions targeted >25 mechanisms, most commonly motivation, defeatist beliefs, activity levels, social communication, and expressive difficulties. Most studies (k = 23) reported positive effects on negative symptoms, though effects were often not sustained at follow-up and outcome measures varied widely. Several theoretically grounded approaches-such as behavioural activation, CBT-based interventions, positive-emotion focused, and emerging digital or VR-supported therapies-showed promising but very preliminary evidence. CONCLUSIONS: There are targeted psychosocial interventions for the negative symptoms of schizophrenia showing promising results despite methodological limitations. Encouragingly many of these interventions seem to adopt a mechanistic approach, with specific adaptations to support engagement and effectiveness in this population. These interventions urgently need further optimisation and testing in large, rigorous randomised controlled trials to support wider implementation.
Yang Q, Wu HQ, Zhu ZH
… +8 more, Yin XY, Hou WL, Man LJ, Bian W, Wang HY, Zhang H, Yu X, Hui L
Schizophr Res
· 2026 Aug · PMID 42068940
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The Disrupted-in-Schizophrenia 1 (DISC1) gene and negative symptoms in schizophrenia are both implicated in neurodevelopmental abnormalities. However, their relationship remains unclear. Thus, this study aimed to compare...The Disrupted-in-Schizophrenia 1 (DISC1) gene and negative symptoms in schizophrenia are both implicated in neurodevelopmental abnormalities. However, their relationship remains unclear. Thus, this study aimed to compare plasma DISC1 levels and negative symptoms severity between first-episode schizophrenia (FDS) patients and healthy controls (HCs), and examine their association. Sixty-six FDS patients meeting the DSM-IV diagnostic criteria, and 66 age- and sex-matched HCs were enrolled in this case-control study. Plasma DISC1 protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Negative symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS). Compared to HCs, patients showed significantly higher CAINS scores for Motivation and Pleasure (MAP, F (1,130) = 5.24, p = 0.02), Expression (EXP, F (1, 130) = 33.89, p < 0.001), and total symptoms (F (1, 130) = 15.14, p < 0.001), alongside lower plasma DISC1 levels (F (1, 130) = 4.622, p = 0.034) after adjusting for convariates. Plasma DISC1 levels were negatively correlated with EXP score in patients (r = -0.30, p = 0.02), but not shown in HCs (r = -0.14, p = 0.26). Multiple linear regression identified lower plasma DISC1 levels as an independent predictor of higher EXP score in patients (β = -3.46, t = 2.23, p = 0.03), but not in HCs (β = 0.15, t = 0.29, p = 0.77). These findings suggest that reduced plasma DISC1 levels in FDS patients are significantly associated with greater expressive deficits, further supporting a potential role for DISC1 in the neurobiology of negative symptoms of schizophrenia.
Liu Y, Wang Y, Tian S
… +6 more, Hu X, Tian J, Wang Y, Mackay LE, Wang W, Gao C
Schizophr Res
· 2026 Aug · PMID 42066662
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OBJECTIVES: Allostatic load (AL) and sleep patterns are linked to severe mental illness (SMI), though their exact mechanisms remain unclear. This study investigated the impact of AL, sleep behavior, and genetic susceptib...OBJECTIVES: Allostatic load (AL) and sleep patterns are linked to severe mental illness (SMI), though their exact mechanisms remain unclear. This study investigated the impact of AL, sleep behavior, and genetic susceptibility on the incidence of SMI (schizophrenia and bipolar disorder). METHODS: The study included 304,884 (schizophrenia) and 304,335 (bipolar disorder) participants from UK Biobank free of SMI at baseline. AL was measured using 10 biomarkers of metabolic, cardiovascular, and inflammatory system. Sleep patterns was derived from five sleep behaviors. Cox models were used to examine the independent and joint effects between AL, sleep patterns, genetic susceptibility, and SMI incidence. RESULTS: After a median 13.7-year follow-up, 220 schizophrenia and 460 bipolar disorder cases were identified. High AL was significantly increased SMI risk, while unhealthy sleep pattern significantly increased the risk of bipolar disorder. Participants with high AL and unhealthy sleep had the highest risk (schizophrenia: HR = 2.44, 95% CI: 1.01-5.88; bipolar disorder: HR = 6.94, 95% CI: 4.22-11.22). Genetic high-risk individuals with high AL (schizophrenia: HR = 5.11, 95% CI: 2.80-9.34; bipolar disorder: HR = 5.07, 95% CI: 3.20-8.02) or unhealthy sleep (schizophrenia: HR = 6.61, 95% CI: 2.60-16.84; bipolar disorder: HR = 11.19, 95% CI: 5.85-21.40) showed elevated susceptibility. AL and genetic risk had an additive interaction effect on the risk of schizophrenia. CONCLUSIONS: High AL and unhealthy sleep are associated with increased SMI risk and amplify genetic susceptibility. Addressing both factors may be crucial for prevention.
van der Walt K, Campbell M, Susser E
… +12 more, Jonker D, Wootton O, McClellan JM, Andreassen OA, Ramesar R, Zingela Z, Morawej Z, Ori R, Mwesiga EK, Gur RC, Stein DJ, Rokicki J
Schizophr Res
· 2026 Aug · PMID 42061216
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BACKGROUND: Catatonia is a severe neuropsychiatric syndrome characterized by profound state-related abnormalities in sensorimotor and cognitive-behavioral function. Overt catatonia is usually successfully treated with be...BACKGROUND: Catatonia is a severe neuropsychiatric syndrome characterized by profound state-related abnormalities in sensorimotor and cognitive-behavioral function. Overt catatonia is usually successfully treated with benzodiazepines or electroconvulsive therapy, but preliminary studies indicate that subtle cognitive and sensorimotor deficits may persist. However, the literature characterizing these deficits has been inconsistent and limited by low sample sizes. Furthermore, no studies have been conducted in the low- and middle-income setting, where catatonia may be more prevalent. METHODS: We examined the relationships between neurocognitive performance and schizophrenia with and without catatonia in a large South African cohort of n = 2853 participants: controls (n = 1426), schizophrenia without catatonia (SCZ, n = 1314), and schizophrenia with a history of catatonia (CAT, n = 113). Participants completed tasks assessing executive function, complex cognition, episodic memory, social cognition and sensorimotor speed, using the University of Pennsylvania Computerized Neurocognitive test battery. Multivariable logistic regressions adjusted for age, age, sex and region of recruitment tested for associations between cognitive performance and study group. RESULTS: Both patient groups performed worse on all domains versus controls (FDR-adjusted p < 0.05). Critically, in the pairwise comparison between SCZ and CAT, sustained attention accuracy was lower in CAT, with higher accuracy scores associated with reduced odds of catatonia (OR = 0.72 CI 0.57-0.91, FDR-adjusted p = 0.01). CONCLUSIONS: These findings suggest that catatonia is associated with distinct and persistent attentional deficits beyond those seen in schizophrenia alone, which warrants confirmation in prospective samples and exploration across other diagnostic categories.
Verdoux H, Schulte P, Lepetit A
… +2 more, Montastruc F, de Leon J
Schizophr Res
· 2026 Aug · PMID 42055527
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OBJECTIVES: The safety profile of clozapine raises specific questions regarding risk and management of cancer. We aimed to synthesize the information on cancer in clozapine users relevant for clinical practice. METHODS:...OBJECTIVES: The safety profile of clozapine raises specific questions regarding risk and management of cancer. We aimed to synthesize the information on cancer in clozapine users relevant for clinical practice. METHODS: Articles were identified with MEDLINE and Web of Sciences from inception through December 2025 (PROSPERO CRD420251247617). We included articles on cancer addressing issues related to risk, diagnosis and treatment of cancer in clozapine users, and management of drug-drug interactions (DDI) and adverse drug reactions. Data were synthesized narratively. RESULTS: We identified 73 articles of which most were case reports (n = 41). Long-term clozapine use is associated with a small increased risk of hematological malignancies (HM), but the existence of a causal link, if any, is not yet established. The literature on cancer care is mostly focused on the risk of neutropenia. Initiating myelosuppressive anti-cancer drugs should not lead to clozapine discontinuation, since there is no evidence of any additive interaction, and adequate curative or palliative treatment of cancer may be dramatically impeded by psychotic decompensation. Few studies have investigated other potentially lethal risks associated with clozapine use at all stages of cancer, such as constipation or intoxication due to DDI or cancer-related factors (smoking cessation, weight loss, inflammation, etc.). CONCLUSIONS: Considering the reduced mortality associated with clozapine use, the very low absolute risk of HM should not discourage its use. Further studies are needed to determine the most effective strategies for preventing, diagnosing, and treating cancer in clozapine users, in order to provide clinicians with structured guidelines.
Hazelton K, Stein A, Gallardo M
… +4 more, Fernandes D, Clouston S, Kotov R, Jonas K
Schizophr Res
· 2026 Aug · PMID 42055525
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INTRODUCTION: Cognitive impairment is common among individuals with schizophrenia. However, it is unclear whether these impairments reflect perturbed neurodevelopmental or neurodegenerative processes. While crystallized...INTRODUCTION: Cognitive impairment is common among individuals with schizophrenia. However, it is unclear whether these impairments reflect perturbed neurodevelopmental or neurodegenerative processes. While crystallized cognition is expected to increase over the lifespan, neurodegenerative processes are associated with stalled or declining trajectories of crystallized cognition. Trajectories of crystallized cognition may therefore provide a window into the nature of cognitive impairment in schizophrenia. Previous studies have been limited by small sample sizes, brief follow-up periods, and a lack of data extending into midlife. The present study charted trajectories of crystallized cognition in schizophrenia and other psychotic disorders. METHODS: Participants are from the Suffolk County Mental Health Project, an epidemiological first-admission psychosis cohort. Vocabulary scores were used as a measure of crystallized cognition. Scores were collected from 2-, 20-, 25-, and 28-year follow-ups, and data from 297 people who had vocabulary scores at 2 or more follow-ups were analyzed. Vocabulary score trajectories were estimated using hierarchical linear models. RESULTS: Individuals with schizophrenia did not accrue vocabulary (B = 0.01, 95% C.I. = (-0.02, 0.03), p = 0.631), while those with other psychotic disorders gained one point every 25 years (B = 0.04, 95% C.I. = (0.02, 0.06), p < 0.001). The interaction between time and diagnosis was significant (p = 0.037). Among 144 individuals with schizophrenia, vocabulary scores increased over time in 56, and decreased or remained the same in 88. DISCUSSION: The trajectory of the schizophrenia group's vocabulary scores, coupled with a higher proportion of individuals showing stable or declining crystallized cognition, is consistent with a neurodegenerative process.
de Oliveira CA, Soares MVR, de Pinho CSN
… +12 more, Pinto JP, Frota AF, Moreira ACO, Silva MFS, Batista TO, Hallak JEC, Sheheryar S, Moura AAAN, Sanders LLO, Gallo MBC, de Sousa FD, Macedo DS
Schizophr Res
· 2026 Aug · PMID 42048856
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Biological mechanisms underlying heterogeneous antipsychotic response in schizophrenia remain incompletely understood. In this exploratory cross-sectional study, we applied deep data-independent acquisition LC-MS/MS plas...Biological mechanisms underlying heterogeneous antipsychotic response in schizophrenia remain incompletely understood. In this exploratory cross-sectional study, we applied deep data-independent acquisition LC-MS/MS plasma proteomics to 56 adults initially enrolled (14 per group), including healthy controls and patients meeting TRRIP criteria for treatment-sensitive (TSS), treatment-resistant (TRS), and ultra-treatment-resistant schizophrenia (UTRS). Following proteomic quality control and exclusion of outliers, 52 individuals comprised the final analytical cohort. Proteomic data were analyzed using a layered strategy integrating covariate adjustment, variance partitioning, mediation analysis, monotonicity filtering, LASSO stability assessment, and redundancy reduction. More than 1400 plasma proteins were quantified; 450 differed across groups before adjustment, and 310 reviewed proteins remained significant after covariate modeling. A sensitivity-associated profile distinguishing TSS from controls (CRP, CCDC62, FBXW7, GULP1, CALD1, COPS6) was consistent with lower inflammatory tone and relative preservation of proteostatic and cytoskeletal regulation. In contrast, a resistance-associated profile separating TRS/UTRS from TSS (SHROOM1, MYH7, ABR, EZR, SERPINF2) converged on cytoskeletal organization, actin-membrane dynamics, and extracellular regulatory processes. Directionally concordant but quantitatively amplified changes were observed in UTRS relative to TRS, although multivariate separation between resistant subgroups was limited after full covariate adjustment. Several proteins enriched in resistant groups corresponded to intracellular or nuclear factors rarely detected in plasma and require cautious interpretation. Overall, these findings are compatible with a progression-like molecular pattern in which treatment sensitivity and resistance may reflect shifts in cellular adaptability and structural regulation. Replication in larger and longitudinal cohorts is required.
Antens MHH, Kamperman AM, van Aken BC
… +2 more, Castelein S, Mulder CL
Schizophr Res
· 2026 Aug · PMID 42048855
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BACKGROUND: Individuals with mild intellectual disability or borderline intellectual functioning (MID/BIF) and schizophrenia spectrum disorder (SSD) may encounter unique challenges that can hinder their personal recovery...BACKGROUND: Individuals with mild intellectual disability or borderline intellectual functioning (MID/BIF) and schizophrenia spectrum disorder (SSD) may encounter unique challenges that can hinder their personal recovery. This study investigates differences in personal recovery and its subdomains over time between individuals with and without an MID/BIF indication. METHODS: Data from two measurements (baseline and one-year follow-up) from the UP's cohort study were used. The sample included 344 individuals with SSD (Male = 65.7%, Female = 34.3%, mean age = 41.2, SD = 12.4), of whom 42.4% had an MID/BIF indication. Personal recovery was assessed with the Individual Recovery Outcomes Counter (I.ROC), both at total scale and across the subdomains Home, Opportunity, People, and Empowerment. The Screener for Intelligence and Learning disabilities (SCIL) identified an indication of MID/BIF. Linear mixed models examined the impact of MID/BIF on personal recovery over time. RESULTS: Participants with MID/BIF scored significantly lower on personal recovery (β = -0.31, p = .003), with the most pronounced difference observed on the empowerment subscale (β = -0.39, p < .001). A significant interaction between time and MID/BIF (β = 0.23, p = .049) suggested that recovery may evolve differently across groups. All effects remained significant after adjusting for age, sex, and psychotic symptom severity. CONCLUSIONS: Individuals with SSD and an MID/BIF indication report lower levels of personal recovery, especially in areas related to social inclusion and empowerment. These findings highlight the need for routine screening on MID/BIF and tailored, inclusive recovery-oriented care that fosters autonomy and empowerment for individuals with MID/BIF.
Cheng L, Xu X, Yang H
… +9 more, Du J, Sheng L, Li X, Han Y, Cheng X, Yang Y, Wang C, Lv L, Li W
Schizophr Res
· 2026 Aug · PMID 42024996
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OBJECTIVE: Predicting early symptom severity and treatment response in schizophrenia is crucial for selecting optimal therapeutic strategies. This study aimed to develop machine learning (ML) models utilizing functional...OBJECTIVE: Predicting early symptom severity and treatment response in schizophrenia is crucial for selecting optimal therapeutic strategies. This study aimed to develop machine learning (ML) models utilizing functional near-infrared spectroscopy (fNIRS) to predict clinical symptoms, cognitive function, and treatment responses. METHODS: We enrolled 139 acutely ill schizophrenia patients and collected fNIRS data alongside clinical measures before and after a 4-week course of antipsychotic treatment. Based on the connectome-based predictive modeling (CPM) framework, regression models were constructed to predict symptom severity and cognitive function, while classification models were built to distinguish treatment response. All models were evaluated using a leave-one-out cross-validation. RESULTS: The models demonstrated significant predictive power for clinical symptoms, cognitive function, and improvement (p < 0.001). However, the predictive efficacy for negative symptoms was relatively limited across all models (optimal model: r = 0.242, p < 0.05). All the classification models exhibited high sensitivity (>84%). The Support Vector Machine achieved an accuracy of 77.5%, and the Random Forest model achieved an area under the curve of 0.914. CONCLUSION: This study indicates that integrating fNIRS with ML not only deepens our understanding of the heterogeneity of schizophrenia but also enhances the accuracy of predicting disease severity and treatment outcomes. This provides a potential objective and reliable clinical tool for precision medicine in schizophrenia.
Wei Y, Huang Y, Cui H
… +9 more, Xu L, Wei Y, Tang X, Tang Y, Hu H, Zhang T, Liu Y, Wang J, Wang Y
Schizophr Res
· 2026 Aug · PMID 42019314
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BACKGROUND: Schizophrenia (SCZ) exhibits considerable overlap with other psychiatric disorders in clinical symptoms and brain structural abnormalities, yet the relationship between these shared neuroanatomical patterns a...BACKGROUND: Schizophrenia (SCZ) exhibits considerable overlap with other psychiatric disorders in clinical symptoms and brain structural abnormalities, yet the relationship between these shared neuroanatomical patterns and individual clinical manifestations remains poorly understood. METHODS: We conducted a longitudinal study of 100 first-episode SCZ patients and 97 healthy controls (HCs), acquiring structural magnetic resonance imaging data at baseline and post antipsychotic treatment. Using normative modeling and summary statistics from eight psychiatric disorders, we computed a cross-disorder regional vulnerability index (RVI) that captures morphological similarity patterns across eight psychiatric disorders at the individual level. RESULTS: We found that SCZ patients demonstrated the highest RVI to bipolar disorder, major depressive disorder, and obsessive-compulsive disorder, with similarity levels increasing over the disease course. Cross-disorder RVI effectively discriminated SCZ patients from HCs, achieving classification accuracies of 0.83 at baseline and 0.87 at follow-up. Particularly, cross-disorder RVIs significantly correlated with symptom severity (p = 0.005), revealing divergent associations between positive and negative syndrome scales. Baseline cross-disorder RVI also predicted the improvement of negative syndrome following antipsychotic treatment (p = 0.021). CONCLUSIONS: These findings highlight the potential of cross-disorder brain similarity profiling to improve personalized diagnosis and treatment in individuals with SCZ.