Schizophr. Res. [JOURNAL]
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200 papers
Quality evaluation of randomized controlled trials of antipsychotic drugs for schizophrenia published in Chinese journals.
Dong Y, Wang J, Guan S … +10 more , Zhu Y, Qin M, Rodolico A, Siafis S, Bighelli I, Davis JM, Priller J, Leucht S, Li C, Schneider-Thoma J
Schizophr Res · 2026 Jul · PMID 42392013 · Publisher ↗
BACKGROUND: The number of randomized-controlled trials (RCTs) originating from China is considerable. However, linguistic barriers and concerns regarding methodological rigor impede their inclusion in meta-analyses. METH...
BACKGROUND: The number of randomized-controlled trials (RCTs) originating from China is considerable. However, linguistic barriers and concerns regarding methodological rigor impede their inclusion in meta-analyses. METHODS: We searched 5 major Chinese databases for RCTs investigating antipsychotics in schizophrenia and contacted study authors to request information about reliability and methods of randomization and blinding using a semi-structured telephone interview and a specifically-designed online questionnaire in Chinese. RESULTS: Among 11,306 articles, 5117 purported RCTs were eligible. After 1232 telephone calls, 698 emails and 7126 letters, 378 authors responded on 349 studies (response rate: 6.9% of 5117 studies). Of those 29 (8.3%) employed randomization procedures and 35 (10.0%) blinding methods with low risk of bias. 125 (35.8%) used suboptimal randomization methods with high risk of bias. In 83 (23.8%) claimed RCTs clinicians chose the antipsychotic based on patients' symptoms and side effects indicating an observational instead of a randomized study design. For 13 (3.7%) modification of some specific outcome data was revealed and for 15 (4.3%) authors indicated that the study results are not reliable. For 57 (16.3%), authors answered "Not sure" to the direct question whether the trial was conducted in reality. There was no clear improvement of quality from 1998 to 2024. CONCLUSION: The main limitations of the study are the low response rate, which reduces representativeness, and that many authors answered they cannot recall which introduces uncertainty. From the answers received, it appears that the methodological quality of many RCTs on antipsychotics in schizophrenia published in Chinese language journals is limited despite initiatives of Chinese research institutions. Therefore, it is advisable that systematic reviewers seek direct confirmation of trial methodology before including Chinese studies in evidence synthesis and perform sensitivity analyses. Moreover, further training for Chinese clinical researchers and stricter quality assurance mechanisms by research institutions and publishers appear warranted.
FL-SDGIN: A federated graph learning approach for schizophrenia diagnosis integrating static and dynamic brain functional networks.
Yang M, Huang J, Liu L … +3 more , Yi C, Chen J, Fan YS
Schizophr Res · 2026 Jul · PMID 42392012 · Publisher ↗
Recent magnetic resonance imaging (MRI) studies have revealed connectivity abnormalities in brain networks of schizophrenia (SZ). Graph Neural Networks (GNN) through their powerful graph embedding ability provide novel a...
Recent magnetic resonance imaging (MRI) studies have revealed connectivity abnormalities in brain networks of schizophrenia (SZ). Graph Neural Networks (GNN) through their powerful graph embedding ability provide novel approaches for brain network analysis in SZ. However, current functional MRI (fMRI) based SZ diagnostic models exhibit limitations including insufficient utilization of static and dynamic functional connectivity (FC/dFC), inadequate modeling of dynamic features while neglecting temporal variability, and lack of consideration for multi-site data privacy and heterogeneity. To address these issues, we propose a federated learning-based static-dynamic graph isomorphism network (FL-SDGIN) for SZ diagnosis. The framework first employs temporal convolutional networks to extract temporal variability of dFC, constructing temporal variability guided attention adjacency matrices. Dynamic graph isomorphism networks (DyGIN) then capture spatiotemporal topological patterns, while graph isomorphism networks (GIN) extract static topological features, enabling multidimensional characterization of brain networks. Simultaneously, federated averaging (FedAvg) is employed for cross-site model training while avoiding direct sharing of raw imaging data. Experimental results under random cross-validation show that FL-SDGIN achieves a classification accuracy of 0.815 and outperforms the evaluated baseline models. Additional leave-one-site-out analysis indicates that cross-site generalization remains challenging under site and cohort heterogeneity. The interpretability analysis suggests that candidate SZ-related regions include the thalamus, posterior cingulate gyrus, postcentral gyrus, middle temporal gyrus, and superior temporal gyrus.
Weight loss and gut microbial changes associated with semaglutide among people living with schizophrenia receiving clozapine or olanzapine: An open-label 24-week semaglutide intervention and 76-week trial.
Lappin JM, Bolton P, Smith G … +11 more , Chua XY, Grattan S, Samaras K, Day R, Popovic G, O'Donnell M, Buten S, Hansen J, Teasdale S, Wong T, El-Omar E
Schizophr Res · 2026 Jun · PMID 42372344 · Publisher ↗
OBJECTIVES: In individuals with schizophrenia receiving either clozapine or olanzapine, this study examined changes in 1) body weight and other cardiometabolic measures and microbiota biodiversity and composition between...
OBJECTIVES: In individuals with schizophrenia receiving either clozapine or olanzapine, this study examined changes in 1) body weight and other cardiometabolic measures and microbiota biodiversity and composition between commencement and completion of 24-week semaglutide intervention; 2) body weight between commencement and 76-week follow-up. METHODS: 24-week intervention (16-weeks full-dose (1.0 mg/week) after 8-weeks' titration) of open-label nurse-administered semaglutide in a public mental health setting, with one-year post-intervention follow-up (76-week trial-completion). PARTICIPANTS: people with schizophrenia without diabetes receiving clozapine or olanzapine with BMI > 27 kg/m. PRIMARY ENDPOINTS: %body weight change at 24-weeks, and 76-weeks. Secondary endpoints: %change in waist circumference, HbA1c at 24-weeks and 76-weeks, body composition at 24-weeks. Gut microbiota changes were compared at baseline, 10-weeks and 24-weeks intervention completion. RESULTS: Mean age: 41.5 years (range 18-61), 65.4% female. Intervention completed by 65.4% (n = 17/26). 24-week intervention: intention-to-treat body weight reduction: -9.8% (95% CI: [-12.7%, -6.8%], p < 0.001) or - 10.1 kg (95% CI [-13.6, -6.6]); waist circumference reduction: -7.3% (95% CI: [-10.1%, -4.4%], p < 0.001); HbA1c non-significant reduction: -5.3% (95% CI [-10.4%, 0.1%], p = 0.055). Microbial alpha diversity decreased as time on semaglutide increased, with enrichment of Parasutterella excrementihominis. Trial completion: 88.2% (n = 15/17). Average body weight change baseline-76-weeks: -5.1% (95% CI: [-8.3%, -1.9%], p = 0.001) or - 5.3 kg (95% CI: [-8.9, -1.7]). DISCUSSION: Semaglutide was associated with significant weight loss in overweight/obese people with schizophrenia. These benefits attenuated following semaglutide discontinuation. Gut microbial compositional differences consistent with improvement in health outcomes may occur in semaglutide-treated people living with schizophrenia.
Converting negative symptom dimension scores across SANS and PANSS.
Kamalakannan SOMV, Lee J, Lella A … +12 more , Belger A, Bustillo JR, Mathalon DH, Ford JM, Lim KO, Preda A, Potkin SG, Ahmed AO, Strauss GP, Calhoun VD, Turner JA, van Erp TGM
Schizophr Res · 2026 Jun · PMID 42372343 · Publisher ↗
Several factor-analytic studies of the Scale for the Assessment of Negative Symptoms (SANS) and Positive and Negative Syndrome Scale (PANSS) have identified two dimensions. These dimensions reflect expressive (EXP) and e...
Several factor-analytic studies of the Scale for the Assessment of Negative Symptoms (SANS) and Positive and Negative Syndrome Scale (PANSS) have identified two dimensions. These dimensions reflect expressive (EXP) and experiential or Motivation and Pleasure (MAP) negative symptoms. However, the extent to which these factor solutions yield similar dimension scores across the two scales remains unclear. This study compared equipercentile linking and linear regression data harmonization methods for cross-scale EXP and MAP conversions and evaluated their accuracy and reliability. While conversions between methods were similar, regression provided a slight edge over equipercentile linking in most comparisons. Most conversions had moderate or better reliability (ICC > 0.6, p < 0.01). EXP conversions generally had higher ICCs than MAP, with EXP >60% and MAP <60% posterior probability of exceeding ICCs>0.75. Some factor score conversions yielded higher reliability than others. However, when considering both EXP and MAP together, Ahmed's factor scores for SANS and Jang's or Khan's for PANSS performed the best. This study is the first to compare equipercentile linking and regression frameworks for scale harmonization as well as to examine the conversion reliability and accuracy for the EXP and MAP dimensions across SANS and PANSS. It is also the first to employ a Bayesian approach, which provides additional information through probability distributions for choosing the most favorable conversion. The conversion formulae from this study and their reported metrics lay the groundwork for analyses of the EXP and MAP even when assessed with different clinical scales.
Inflammation-associated alterations in mGluR transcript expression in the human nucleus accumbens independent of schizophrenia diagnosis.
Walpole SJ, Lum JS, Chesworth R … +4 more , Walker AK, Karl T, Shannon Weickert C, Newell KA
Schizophr Res · 2026 Jun · PMID 42364358 · Publisher ↗
Metabotropic glutamate receptors (mGluRs) are of increasing interest in the pathophysiology and treatment of schizophrenia. In the nucleus accumbens (NAc), presynaptic mGluRs (largely group II and III) can regulate the a...
Metabotropic glutamate receptors (mGluRs) are of increasing interest in the pathophysiology and treatment of schizophrenia. In the nucleus accumbens (NAc), presynaptic mGluRs (largely group II and III) can regulate the activity of medium spiny neurons (MSNs) through control of glutamate release from extra-striatal regions. Given that inflammatory pathways can modulate glutamate and dopamine signalling, inflammation may influence these mGluR-mediated mechanisms in schizophrenia. Cellular expression of mGluR mRNAs in the NAc was investigated using a publicly available single-nucleus RNA sequencing dataset. Frozen NAc tissue from individuals with schizophrenia (n = 30) and controls (n = 30) were obtained from the New South Wales Brain Tissue Resource Centre. Protein levels of glutamate receptors, mGluR2, mGluR3, mGluR4, mGluR7, and a dopamine synthesis enzyme, tyrosine hydroxylase (TH) were quantified by western blot. mGluR transcripts were measured using qRT-PCR. Neuroinflammatory status was determined from levels of pro-inflammatory transcripts (SERPINA3, IL6, IL1β, and TNFα). TH protein levels were elevated in the NAc of individuals with schizophrenia. GRM1, GRM3, GRM4, GRM7 and GRM8 transcripts were strongly expressed in MSNs and inhibitory neurons. Gene and protein expression of the mGluRs did not differ between schizophrenia and controls. When the cohort was stratified into a high (n = 13) and a low (n = 42) inflammation group, GRM1 and GRM5 mRNAs were decreased in those with high inflammation. These data indicate that elevated inflammation, irrespective of schizophrenia diagnosis, is associated with a selective reduction of group I mGluR transcripts in the NAc. This suggests that inflammation may be a key modulator of glutamatergic signalling in this region.
One social interaction after another: Dynamic modeling of social experience in schizophrenia.
Weittenhiller LP, Abplanalp SJ, Green MF … +3 more , Reavis EA, Granholm E, Catalano LT
Schizophr Res · 2026 Jun · PMID 42361674 · Publisher ↗
Social dysfunction in schizophrenia reflects not only the frequency of social contact but also the quality of interactions when they occur, and their impact on social experience. This study employed ecological momentary...
Social dysfunction in schizophrenia reflects not only the frequency of social contact but also the quality of interactions when they occur, and their impact on social experience. This study employed ecological momentary assessments (EMA), anchored to social interactions in daily life, to examine components of social experience: perceived acceptance, self-confidence, consummatory pleasure, negative affect, and motivation for future social engagement. Veterans with (n = 34) and without schizophrenia (n = 31) completed smartphone EMA five times per day for seven days. Multilevel vector autoregressive (mlVAR) network models estimated contemporaneous associations within interactions, temporal associations across successive interactions, and centrality of each component within the resulting networks. The contemporaneous networks showed that perceived acceptance within an interaction was associated with more enjoyment and greater social motivation in both groups. Centrality analyses for contemporaneous networks indicated that consummatory pleasure and perceived acceptance showed the greatest relative association with other network components within an interaction for both groups. The temporal networks showed that social motivation persisted across interactions and predicted more enjoyment and higher self-confidence at subsequent interactions in both groups. Descriptively, group differences emerged for negative affect, which was more temporally persistent across interactions in schizophrenia. Centrality analyses for temporal networks indicated that social motivation was most strongly connected to subsequent social experience components across interactions in both groups. Together, findings from contemporaneous and temporal networks highlight the roles that social motivation and negative affect play in shaping social experience within and across interactions in schizophrenia.
Reduced synaptic plasticity and E/I imbalance drive peripersonal space boundaries expansion in schizophrenia.
Paredes R, Grigoras V, Ferroni F … +3 more , Ardizzi M, Ferri F, Seriès P
Schizophr Res · 2026 Jun · PMID 42349163 · Publisher ↗
Abnormal encoding of peripersonal space (PPS) is believed to affect bodily self disruptions in schizophrenia (SCZ). Empirical studies show that SCZ patients exhibit a narrower PPS than controls but maintain its plasticit...
Abnormal encoding of peripersonal space (PPS) is believed to affect bodily self disruptions in schizophrenia (SCZ). Empirical studies show that SCZ patients exhibit a narrower PPS than controls but maintain its plasticity. Computational research links this smaller PPS to increased excitation of sensory neurons and reduced feedforward synaptic density. However, it is unclear how such differences influence learning during the expansion of PPS boundaries. We hypothesise that Hebbian plasticity can account for PPS expansion after active tool use training. To explore the effect of such mechanisms on PPS plasticity, we developed a SCZ network model which was fit to behavioural data before and after tool manipulation. We found that PPS expansion occurs in spite of E/I imbalance or reduced synaptic density, but does not match the post-training PPS representation of patients. A better fit was obtained after altering plasticity by either reducing the learning rate, increasing the forgetting rate or increasing the plasticity threshold. We discuss our findings in terms of dysfunctional plasticity in SCZ and highlight the key challenges in identifying the neurobiological correlates of reduced plasticity within PPS networks. Because current empirical data supports multiple viable mechanisms, we propose experiments to distinguish between the proposed plasticity accounts and clarify mixed findings on PPS representation in SCZ.
Complete blood count-derived inflammatory markers and symptom phenotypes in schizophrenia spectrum disorders: A hierarchical clustering analysis.
Cavaleri D, Crocamo C, Cucchi G … +2 more , Bartoli F, Carrà G
Schizophr Res · 2026 Jun · PMID 42320354 · Publisher ↗
BACKGROUND: Schizophrenia spectrum disorders (SSDs) show substantial clinical heterogeneity, potentially reflecting distinct pathophysiological mechanisms. Peripheral immune-inflammatory alterations have been implicated...
BACKGROUND: Schizophrenia spectrum disorders (SSDs) show substantial clinical heterogeneity, potentially reflecting distinct pathophysiological mechanisms. Peripheral immune-inflammatory alterations have been implicated in SSDs, yet their links with specific clinical phenotypes remain largely unexplored. This study thus aimed to examine associations between complete blood count-derived inflammatory markers and symptom patterns in inpatients with SSDs. METHODS: This cross-sectional study included inpatients with SSDs. Hierarchical clustering was applied to Positive and Negative Syndrome Scale (PANSS) five-factor scores to identify symptom-based phenotypes. Six markers - neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) - were compared across clusters using analysis of variance and multivariable linear regressions. RESULTS: Among 454 inpatients with SSDs aged 18-65, three clusters emerged: Positive/excited-dominant (n = 185, 40.8%), Negative/disorganised/depressive-dominant (n = 133, 29.3%), and Balanced (n = 136, 30.0%). All inflammatory markers significantly differed across clusters: NLR (F = 3.29, p = 0.038), MLR (F = 11.13, p < 0.001), PLR (F = 3.71, p = 0.025), SII (F = 3.34, p = 0.036), SIRI (F = 7.42, p < 0.001), and AISI (F = 6.49, p = 0.002). The Negative/disorganised/depressive-dominant cluster exhibited the most pronounced inflammatory profile, with covariate-adjusted increases compared to the Balanced cluster of +30% for MLR (p = 0.001), +20% for PLR (p = 0.040), +32% for SII (p = 0.043), +43% for SIRI (p = 0.011), and +52% for AISI (p = 0.015). The Positive/excited-dominant cluster showed selective, covariate-adjusted elevations in MLR (+19%, p = 0.020) and SIRI (+29%, p = 0.028) versus the Balanced cluster. CONCLUSIONS: Distinct SSD phenotypes are associated with heterogeneous inflammatory profiles, with monocyte-driven inflammation particularly characterizing negative/disorganised/depressive presentations, probably supporting phenotype-stratified approaches in precision psychiatry.
Moderators of behavioral activation versus treatment as usual effects on negative symptoms in patients with Schizophrenia Spectrum Disorder.
Smagula SF, Kim YS, Lee E … +3 more , Wallace ML, Ferrarelli F, Choi KH
Schizophr Res · 2026 Jun · PMID 42314408 · Publisher ↗
Recent work supports the efficacy of Behavioral Activation (BA) over Treatment as Usual (TAU) for the negative symptoms (NS) of Schizophrenia Spectrum Disorder (SSD). To inform precision medicine approaches, we aimed to...
Recent work supports the efficacy of Behavioral Activation (BA) over Treatment as Usual (TAU) for the negative symptoms (NS) of Schizophrenia Spectrum Disorder (SSD). To inform precision medicine approaches, we aimed to identify factors that moderate the effect of BA versus TAU. We performed discovery-based moderators analyses, leveraging data from a recently completed randomized controlled trial that found BA had efficacy over TAU for NS. Potential moderators were pre-treatment symptom items from common symptom scales, including items from the Clinical Assessment Interview for Negative Symptoms [13], the Positive and Negative Syndrome Scale [14] (PANSS), and the Brief Negative Symptom Scale. Seven PANSS items emerged as potential negative moderators, wherein greater severity of these symptoms was associated with lower efficacy of BA versus TAU (effect size estimate range: -0.45 to -0.25). These negative moderators were conceptual disorganization, hallucinatory behavior, grandiosity, anxiety, tension, uncooperativeness, and unusual thought content. Using total scores on these items as a combined moderator revealed a minority subgroup, composed of 20% of the overall sample, in whom rates of response to TAU and BA were roughly equal (response rates: TAU, 60%; BA, 50%). In contrast, among the majority subgroup (80% of the sample), BA had clear effects above and beyond the TAU condition (response rates: TAU, 20%; BA, 58%). These findings showcase how moderator research informs precision medicine. Specifically, NS appear malleable by adding BA to TAU among patients without uncooperativeness, anxiety, and positive symptoms. However, in the presence of these moderating symptoms, TAU may be equally efficacious.
Therapeutic potential of metabotropic glutamate receptor 7 modulation in correcting cognitive deficits of schizophrenia.
Harris NM, Holter KM, Niswender CM
Schizophr Res · 2026 Jun · PMID 42308865 · Publisher ↗
Cognitive deficits in schizophrenia are a major predictor of patient functional outcome, and current treatments have limited efficacy in targeting this symptom domain. Glutamatergic dysfunction is hypothesized to contrib...
Cognitive deficits in schizophrenia are a major predictor of patient functional outcome, and current treatments have limited efficacy in targeting this symptom domain. Glutamatergic dysfunction is hypothesized to contribute to cognitive impairments, and administration of N-methyl-d-aspartate (NMDA) receptor antagonists to both healthy humans and animals causes behavioral and cognitive deficits similar to those observed in patients with schizophrenia. In particular, hypofunction of NMDA receptors on GABAergic interneurons in the medial prefrontal cortex (mPFC) leads to excessive pyramidal cell activity and is a hypothesized mechanism underlying these deficits. As such, therapeutic modulation of glutamatergic and GABAergic release in PFC-associated circuits may correct cognitive impairments in schizophrenia. Metabotropic glutamate (mGlu) receptors have emerged as a promising strategy to target this symptom domain due to their widespread expression in relevant brain regions and their implications within the glutamate system. Group III mGlu receptors (mGlu) are G-coupled receptors which predominantly show presynaptic localization and are well-positioned to modulate both glutamatergic and GABAergic neurotransmission. In particular, mGlu is widely expressed throughout the central nervous system, including expression on neurons within relevant PFC circuits. Interestingly, schizophrenia and other neuropsychiatric disorders characterized by cognitive deficits are associated with loss-of-function variants in GRM7, the gene encoding mGlu. Furthermore, both mGlu potentiation and inhibition have shown efficacy in preclinical models of neurodevelopmental and neuropsychiatric disorders characterized by cognitive impairments. Therefore, mGlu is proposed to be a viable therapeutic target to treat cognitive deficits driven by glutamatergic dysfunction in disorders including schizophrenia.
Increased brain VDAC1 protein levels correlate with behavioural performance in a ketamine murine model of schizophrenia and are attenuated by the mGluR2 modulator JNJ-46356479.
Olivares-Berjaga D, Rodríguez N, Martínez-Pinteño A … +4 more , Rubio-Unguetti L, Parellada E, Gassó P, Morén C
Schizophr Res · 2026 Jun · PMID 42302697 · Publisher ↗
BACKGROUND: Schizophrenia (SZ) is a neurodevelopmental disorder involving excitatory/inhibitory imbalance and apoptotic dysregulation. VDAC1, a voltage-dependent anion channel protein located in the mitochondrial outer m...
BACKGROUND: Schizophrenia (SZ) is a neurodevelopmental disorder involving excitatory/inhibitory imbalance and apoptotic dysregulation. VDAC1, a voltage-dependent anion channel protein located in the mitochondrial outer membrane, plays a pivotal role in mitochondria-mediated apoptosis. However, its involvement in SZ remains underexplored. OBJECTIVES: This study aimed to investigate VDAC1 protein levels in the prefrontal cortex (PFC) and hippocampus (HPC) of a postnatal ketamine-exposed mouse model of SZ, and to assess the effects of treatment with the metabotropic GLU receptor 2 (mGluR2) positive allosteric modulator JNJ-46356479 (JNJ). We also examined associations between VDAC1 expression, behavioural performance, and other apoptosis-related markers. METHODS: Male and Female C57BL/6 J mice were exposed to ketamine or saline on postnatal days (PND) 7, 9, and 11, and treated in adulthood with JNJ or vehicle. VDAC1 protein levels in the PFC and HPC were quantified by western blot. Previously acquired behavioural data and levels of apoptotic markers (Bax, Bcl-2, caspase-3) from the same animals were analysed in relation to VDAC1 expression. RESULTS: VDAC1 levels were significantly increased in the PFC of ketamine-exposed mice and partially normalised by JNJ treatment. VDAC1 levels in the PFC and HPC were positively correlated. Higher VDAC1 levels were associated with an increased Bax/Bcl-2 ratio and poorer cognitive and social performance, particularly in the Y-Maze and the Five-Trial Social Memory Tests. CONCLUSIONS: Our findings support VDAC1 as a potential molecular marker of apoptotic imbalance in SZ. JNJ treatment may exert neuroprotective effects by modulating VDAC1 levels, suggesting that glutamatergic modulation could offer novel therapeutic avenues targeting mitochondrial dysfunction in SZ.
Utility of zoom-based clinical interviews for automated facial emotion analysis.
Bertrand CE, Gold JM, Waltz JA … +10 more , Schiffman J, Ellman LM, Strauss GP, Walker EF, Woods SW, Powers AR, Kenney J, Corlett PR, Silverstein SM, Mittal VA
Schizophr Res · 2026 Jun · PMID 42302696 · Publisher ↗
Abstract loading — click title to view on PubMed.
Comparative efficacy of oral and long-acting injectable paliperidone on social functioning in schizophrenia: A systematic review and meta-analysis.
Huang Y, Zhang J, Ling J … +3 more , Zhao L, He B, Zhu G
Schizophr Res · 2026 Jun · PMID 42296848 · Publisher ↗
BACKGROUND: Schizophrenia significantly impairs personal and social functioning. Although paliperidone is a first-line antipsychotic available in oral extended-release (ER) and long-acting injectable (LAI) formulations,...
BACKGROUND: Schizophrenia significantly impairs personal and social functioning. Although paliperidone is a first-line antipsychotic available in oral extended-release (ER) and long-acting injectable (LAI) formulations, their comparative effects on functional outcomes remain unclear. METHODS: We conducted a systematic review and meta-analysis of studies (2007-2024) assessing paliperidone's impact on Personal and Social Performance (PSP) scale scores. Included were 20 RCTs and 38 single-arm trials. Three-level meta-analysis with robust variance estimation (RVE) was adopted to handle non-independent repeated outcome data. RESULTS: Meta-analysis of RCTs showed paliperidone significantly improved PSP scores versus placebo (pooled MD = 2.51, 95% CI: 0.23 to 4.80), with within-study heterogeneity (I = 7.72%) and a markedly high between-study heterogeneity (I = 78.25%). Single-arm trials showed a marked mean PSP increase of 9.46 points (95%CI: 7.75-11.17). Subgroup analyses revealed both paliperidone ER (MD = 7.25, 95% CI: 5.52 to 8.99) and LAI (MD = 4.54, 95% CI: 1.75 to 7.33) were superior to placebo, but no significant difference was found between formulations or versus other oral antipsychotics. Improvements in were most prominent in patients with marked baseline difficulties (PSP 31-50, MD = 5.45, 95% CI: 2.89 to 7.91) and in participants receiving short-term follow-up of ≤12 weeks (MD = 5.45, 95% CI: 3.25 to 7.64). CONCLUSION: Paliperidone effectively improves personal and social functioning in schizophrenia, with no functional superiority of long-acting injectables. Formulation choice should be individualized, considering baseline function, illness phase, and adherence, rather than presuming inherent differences in functional efficacy.
Is a higher antipsychotic dose required to treat relapse in remitted first episode psychosis? A systematic review and meta-analysis.
Teague V, Guilfoyle S, Pocha P … +3 more , Chelvam TP, Lally J, O'Donoghue B
Schizophr Res · 2026 Jun · PMID 42296847 · Publisher ↗
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The U-shaped relationships between prolactin level and insulin resistance in patients with schizophrenia under olanzapine treatment.
Goh KK, Wu TH, Chen CH … +2 more , Chen PY, Lu ML
Schizophr Res · 2026 Jun · PMID 42288043 · Publisher ↗
Patients with schizophrenia are at elevated risk for metabolic disturbances, particularly when treated with second-generation antipsychotics such as olanzapine. Prolactin elevation is a common adverse effect of antipsych...
Patients with schizophrenia are at elevated risk for metabolic disturbances, particularly when treated with second-generation antipsychotics such as olanzapine. Prolactin elevation is a common adverse effect of antipsychotic therapy, yet its role in glucose homeostasis remains unclear. This study examined the association between serum prolactin levels and insulin resistance in patients with schizophrenia receiving long-term olanzapine treatment. A cross-sectional study was conducted among 310 patients with schizophrenia maintained on olanzapine monotherapy for ≥6 months. Insulin resistance was calculated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), with a cut-off value of 2.0 indicating insulin resistance. Curve estimation, quartile-based analyses, and multivariate regression models were applied to explore both linear and non-linear associations between prolactin and metabolic indices. The prevalence of metabolic syndrome and hyperprolactinemia was 36.8% and 51.0%, respectively. Prolactin levels were significantly associated with insulin, body mass index (BMI), triglycerides, and HOMA-IR. A quadratic regression model provided the best fit for HOMA-IR, revealing a U-shaped relationship: both low and high prolactin levels were associated with higher insulin resistance. Multivariate analysis confirmed prolactin level and BMI as independent predictors of insulin resistance. Participants were grouped by quartiles of serum prolactin. Compared with Q2, both Q1 and Q4 showed elevated insulin levels and HOMA-IR, indicating nonlinear prolactin-metabolic associations in schizophrenia. This study reveals a U-shaped relationship between prolactin level and insulin resistance in olanzapine-treated schizophrenia. Both hypo- and hyperprolactinemia may be linked to metabolic risk, highlighting the importance of integrated metabolic and endocrine monitoring in psychiatric care.
The effectiveness and tolerability of trauma-focused interventions for trauma symptoms in individuals who have psychosis: A systematic review and meta-analysis.
Mason A, Logeswaran Y, Opper F … +2 more , Khan H, Johns L
Schizophr Res · 2026 Jun · PMID 42284952 · Publisher ↗
BACKGROUND AND HYPOTHESIS: People with psychosis and a trauma history have worse clinical and functional outcomes compared to those without a trauma history. Services often don't provide trauma-focused interventions for...
BACKGROUND AND HYPOTHESIS: People with psychosis and a trauma history have worse clinical and functional outcomes compared to those without a trauma history. Services often don't provide trauma-focused interventions for psychosis. This meta-analysis of randomised controlled trials (RCTs) aimed to compare multiple outcomes of safety, feasibility, acceptability, clinical and cost effectiveness of different trauma-focused therapies (TFTs) for people with psychosis. STUDY DESIGN: For this meta-analysis and systematic review, Embase, PsycINFO and Medline were searched until 5th January 2026 for original RCTs of TFTs for individuals with psychosis, with the design consistent with PRISMA guidelines. Outcomes were the safety, feasibility, acceptability and effectiveness of these treatments. Meta analyses were conducted when at least three studies reported quantitative measures of clinical outcomes. Cochrane Revised Risk of Bias tool for RCTs was used for quality assessment. STUDY RESULTS: Ten RCTs were included. Eye Movement Desensitization and Reprocessing (EMDR), prolonged exposure (PE) and cognitive therapies (CR) were safe, acceptable and cost effective. EMDR vs treatment-as-usual (TAU) significantly reduced positive psychotic symptoms post-treatment, but not at 6-month follow-up (studies = 4, outcomes = 9, g = 0.21, p = 0.05). EMDR significantly reduced PTSD symptoms post-treatment (studies = 3, outcomes = 6, g = 0.84, p < 0.001) and at 6-month follow-up (studies = 4, outcomes = 8, g = 0.63, se = 0.10, p < 0.001) vs TAU. PE showed reductions in PTSD symptoms and paranoia, and CR's showed reductions in PTSD symptoms post-treatment (vs TAU). CONCLUSIONS: EMDR has the most published studies suggesting its potential to be an effective treatment for this population. Further RCTs are required to assess symptom outcomes and healthcare costs of all interventions examined.
Energy metabolism dysregulation in schizophrenia with non-thyroidal illness syndrome: Roles of citric acid and Tyrosol-4-sulfate.
Chen J, Dong Y, Li Y … +7 more , Liu N, Wang X, Han Y, Li Y, Guo Y, Li S, Li J
Schizophr Res · 2026 Jun · PMID 42284951 · Publisher ↗
BACKGROUND: Non-Thyroidal Illness Syndrome (NTIS) is frequently observed in schizophrenia and is traditionally regarded as a peripheral endocrine disturbance. However, whether NTIS reflects a distinct metabolic phenotype...
BACKGROUND: Non-Thyroidal Illness Syndrome (NTIS) is frequently observed in schizophrenia and is traditionally regarded as a peripheral endocrine disturbance. However, whether NTIS reflects a distinct metabolic phenotype linked to central energy dysregulation in schizophrenia remains unclear. We hypothesized that NTIS in schizophrenia reflects a distinct metabolic state characterized by disrupted energy metabolism, which may be linked to specific symptom dimensions. METHODS: A total of 185 patients with schizophrenia were enrolled and classified into NTIS and non-NTIS groups based on standard thyroid hormone criteria. Untargeted metabolomic profiling was performed using ultra-high-performance liquid chromatography high-resolution mass spectrometry. Differential metabolites were identified using Orthogonal-Partial-Least Squares-Discriminant-Analysis and Receiver Operating Characteristic curve analysis, followed by pathway enrichment analyses and regression analyses to examine associations with clinical symptoms. RESULTS: A total of 29 differential metabolites were screened (Variable Importance in Projection > 2, P - correction < 0.05), primarily related to amino acids and organic acids. Pathway enrichment analysis revealed significant perturbations in 10 metabolic pathways, with the TCA cycle (citrate cycle) (impact = 0.261, P < 0.0001). Two metabolites, Citric acid (AUC = 0.701, P < 0.05) and Tyrosol-4-sulfate (AUC = 0.703, P < 0.05) demonstrated good discriminative performance for NTIS status. These 2 metabolites were positively associated with the Visuospatial/Constructional dimension and negatively associated with positive symptoms in the NTIS group. CONCLUSIONS: Schizophrenia patients with NTIS display a distinct metabolic phenotype marked by TCA cycle dysregulation. Citric acid and tyrosol-4-sulfate may serve as metabolic indicators linking thyroid dysfunction to cognitive, psychotic symptoms.
Letter to the editor: Higher anterior cingulate glutamatergic metabolites in schizophrenia with past alcohol use disorders.
Fischer BA, Saadeh M, Roche D … +2 more , Wijtenburg SA, Rowland LM
Schizophr Res · 2026 Jun · PMID 42275850 · Publisher ↗
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Serum Clozapine Levels and Dose-Exposure Relationships in Indian Patients: A Cross-Sectional Study.
Jane GRA, Varughese NR, Prabha R … +1 more , Chichra A
Schizophr Res · 2026 Jun · PMID 42275849 · Publisher ↗
INTRODUCTION: Asians probably need lower doses than Caucasians to reach therapeutic serum clozapine levels. However, heterogeneity within Asians is poorly explored in the literature. There is limited South Asian data to...
INTRODUCTION: Asians probably need lower doses than Caucasians to reach therapeutic serum clozapine levels. However, heterogeneity within Asians is poorly explored in the literature. There is limited South Asian data to guide clinicians treating this population. METHODS: We conducted a cross-sectional study to estimate serum clozapine concentrations in Indians on stable doses. We tested for significant associations using Pearson's correlation and Student's t-test. We calculated target therapeutic dose ranges across sex and smoking status using mean C/D (serum concentration-to-dose) ratios in these patient groups. As a preliminary analysis, we constructed a linear regression model of serum clozapine concentration using variables identified in bivariate analysis and exploratory regression analysis. RESULTS: Eighty-two participants were included. The mean serum clozapine concentration was 703.57 ng/ml (SD = 355.31). The mean C/D ratio was 2.35 ng/ml/mg (SD = 1.11); it was 3.05 in female non-smokers, 1.39 in the single female smoker, 2.31 in male non-smokers, and 1.32 in male smokers. Calculated therapeutic doses ranged from a minimum of 115 mg in female non-smokers to a maximum of 455 mg in male smokers. Sex, smoking status, alcohol use, symptom severity, dose prescribed, and beedi smoking were significantly associated with clozapine pharmacokinetics. The regression model for serum concentrations (including sex, smoking status, and prescribed dose as variables) explained 38.5% of the variance. CONCLUSIONS: South Asians have higher C/D ratios of clozapine compared to Caucasians and East Asians. They require lower doses to achieve therapeutic serum concentrations. Beedi smoking is associated with lower C/D ratios than cigarette smoking.
Predicting transition to psychiatric disorders in clinical high-risk for psychosis subjects using machine learning and facial features.
Loch AA, Queluz FH, Waurzenczak B … +10 more , Gondim JM, Argolo FC, Lopes-Rocha AC, van de Bilt MT, de Jesus LP, Jafet AF, Gattaz WF, Cecchi GA, Corcoran CM, Ara A
Schizophr Res · 2026 Jun · PMID 42269195 · Publisher ↗
BACKGROUND: Clinical-high-risk for psychosis (CHR) status is increasingly viewed as a transdiagnostic risk state, but scalable markers of adverse outcomes remain limited. We tested whether facial dynamics extracted from...
BACKGROUND: Clinical-high-risk for psychosis (CHR) status is increasingly viewed as a transdiagnostic risk state, but scalable markers of adverse outcomes remain limited. We tested whether facial dynamics extracted from baseline videos could predict transition to any psychiatric disorder in CHR individuals. METHODS: In the SSAPP cohort, CHR participants were assessed at baseline with SIPS and SCID-5 and followed for a mean of 22.8 months. Baseline videos from 50 participants were analyzed. Facial landmarks and Action Units were extracted with OpenFace 2.0 from Subject Overview (SO) and Memory Recall (MR) recordings. PCA-derived features and AU summaries were entered into class-weighted logistic-regression models using leave-one-out cross-validation. RESULTS: Of the modelled sample, 29 participants transitioned to a psychiatric disorder, including 9 psychotic and 20 non-psychotic outcomes; 21 did not transition. PCA features from SO videos showed the best performance (F1-score = 72%, sensitivity = 66%, specificity = 76%, balanced accuracy = 71%, MCC = 0.41), outperforming MR-derived and AU-based models. Sensitivity was higher for psychotic transitioners (78%) than for non-psychotic transitioners (60%). Predictive signal was concentrated in higher-order PCA components reflecting subtle facial-motor variation. CONCLUSIONS: Facial dynamics extracted from clinical videos may provide scalable markers of adverse outcomes in CHR populations. Future studies should aim at larger samples and external validation.
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