Schizophr. Res. [JOURNAL]
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200 papers
Treatment of schizotypal disorder: A systematic review and GRADE evaluation of the certainty of evidence.
Gundersen KB, Arnfred B, Albert N … +5 more , Rasmussen AR, Ebdrup BH, Polari A, Nelson B, Glenthøj LB
Schizophr Res · 2026 Feb · PMID 41421074 · Publisher ↗
BACKGROUND: Evidence to guide treatment for schizotypal disorder is scarce, and clinical guidelines remain undeveloped. This systematic review synthesized current evidence on pharmacological and psychotherapeutic interve...
BACKGROUND: Evidence to guide treatment for schizotypal disorder is scarce, and clinical guidelines remain undeveloped. This systematic review synthesized current evidence on pharmacological and psychotherapeutic interventions targeting clinical symptoms, cognition, and functioning in schizotypal disorder. METHODS: We searched PsychINFO, Embase, Medline, and Cochrane Register of Controlled Trials (25/03/2025) without date restrictions, supplemented by handsearching. Eligible studies were screened, quality appraised, and data extracted by two independent authors. Due to substantial heterogeneity, findings were synthesized narratively, and evidence certainty was rated using GRADE. RESULTS: Twenty-one studies met inclusion criteria. Most had some concerns regarding risk of bias. Pharmacological trials most frequently investigated antipsychotics, with preliminary evidence suggesting benefits of thiothixene and, to a lesser extent, risperidone, olanzapine, and haloperidol in reducing general psychiatric symptoms, although effects on depressive symptoms were mixed. Dopamine agonists and central alpha-2A agonists showed domain-specific cognitive improvements, particularly when combined with cognitive remediation therapy and social skills training. Among psychotherapeutic approaches, metacognitively oriented and evolutionary systems therapies demonstrated consistent symptom reductions, while integrated interventions temporarily reduced negative symptoms and psychosis risk. Functional improvements were most evident in multimodal interventions combining pharmacological and psychosocial components. Across interventions, the overall certainty of evidence was graded very low to low. CONCLUSIONS: Current treatment evidence for schizotypal disorder is limited and heterogeneous. Larger, high-quality randomized controlled trials are needed to establish efficacy across clinical, cognitive, and functional domains and to inform development of evidence-based treatment guidelines.
Neighborhood environmental deprivation predicts the generalized neurocognitive deficit in schizophrenia.
Zhang L, Zhang Z, Strauss GP
Schizophr Res · 2026 Feb · PMID 41421073 · Full text
BACKGROUND: The generalized neurocognitive deficit is a core feature of schizophrenia (SZ). However, no current treatments have demonstrated satisfactory efficacy in remediating cognitive impairment in this population. T...
BACKGROUND: The generalized neurocognitive deficit is a core feature of schizophrenia (SZ). However, no current treatments have demonstrated satisfactory efficacy in remediating cognitive impairment in this population. This lack of treatment progress might be due in part to the failure to consider broader environmental factors and social determinants of health. The current paper explored the contributing role of these factors to the generalized neurocognitive deficit in SZ. METHODS: Participants included 114 outpatients with SZ and 117 matched healthy controls (CN) who completed a cross-sectional study. Cognitive impairment was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Environmental deprivation was measured by Area Deprivation Index (ADI). Rurality was measured by the rural urban continuum code (RUCC). A linear regression model was fitted to predict MCCB total score with ADI, RUCC, and the interaction between ADI and RUCC as predictors. RESULTS: The overall model was significant, F = 8.06, p < .001, R = 0.14. The effect of ADI score was also significant, β = -0.36, t = -2.30, p < .05; while the effect of RUCC, β = 0.06, t = 0.34, p = .73, and the interaction between ADI and RUCC, β = -0.001, t = 0.27, p = .99, were nonsignificant. CONCLUSIONS: Neighborhood-level environmental deprivation predicted cognitive impairment in SZ. This highlights the need to incorporate environment-focused interventions when treating cognitive impairment in SZ.
Reevaluating the assessment of nonverbal behavior in psychosis symptomatology: A call for cultural sensitivity.
Schuch JM, Pratt DN, Haase CM … +2 more , Qu Y, Mittal VA
Schizophr Res · 2026 Feb · PMID 41418653 · Full text
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Comparative lipidomic alterations in the anterior cingulate cortex in schizophrenia and major depression.
Senko D, Zavolskova M, Efimova O … +5 more , Morozova A, Zorkina Y, Kostyuk G, Stekolschikova E, Khaitovich P
Schizophr Res · 2026 Jan · PMID 41412002 · Publisher ↗
Schizophrenia and major depressive disorder are typically classified as distinct psychiatric conditions; however, they share overlapping symptoms and biological risk factors. Identifying molecular features that distingui...
Schizophrenia and major depressive disorder are typically classified as distinct psychiatric conditions; however, they share overlapping symptoms and biological risk factors. Identifying molecular features that distinguish or unify these disorders may provide insights into their underlying mechanisms. Lipid metabolism is increasingly recognized as an important factor influencing brain function and the development of mental disorders, yet direct comparative lipidomic analyses of these two conditions remain limited. In this study, we examined the lipidomic profiles of the anterior cingulate cortex (ACC), a region central to emotional regulation and cognitive control, across schizophrenia, major depression and control cohorts. Both disorders showed increased levels of free fatty acids (FA) and lysophosphatidylcholines (LPC). Additionally, major depression was characterized by alterations in glycerolipid classes, whereas schizophrenia exhibited decreased levels of acylcarnitines (CAR). This pattern was further confirmed by targeted analysis of carnitine metabolites. Our results suggest that abnormalities in brain lipid metabolism, particularly in pathways related to cellular energy regulation and glycerolipid remodeling, differ between schizophrenia and depression, providing potential markers to distinguish these disorders and clarify their biological characteristics.
Shared genetic effects among schizophrenia, substance use disorder, and hippocampal volume in a multiplex extended pedigree sample.
Musket CW, Rupert PE, Kuo SS … +8 more , Roalf DR, Prasad KM, Wood J, Gur RC, Almasy LA, Gur RE, Nimgaonkar VL, Pogue-Geile MF
Schizophr Res · 2026 Jan · PMID 41386004 · Publisher ↗
BACKGROUND: Many individuals with schizophrenia have comorbid substance use disorders (SUD) and yet the reasons for this comorbidity are largely unknown. The current study examined if shared genetic effects jointly incre...
BACKGROUND: Many individuals with schizophrenia have comorbid substance use disorders (SUD) and yet the reasons for this comorbidity are largely unknown. The current study examined if shared genetic effects jointly increase risk for both schizophrenia and SUD and if shared genetic effects on brain structure phenotypes mediate this relationship. METHODS: Data were collected using a multiplex extended pedigree design ascertained through schizophrenia probands (total sample N = 1306, with N = 789 relatives and N = 517 unrelated controls) to investigate the degree to which genetic effects are shared among schizophrenia, four SUDs, and structural MRI measures of surface area, cortical thickness, and subcortical volumes. Given that all predictions were directional (e.g., that schizophrenia would be positively genetically correlated with substance use), one-tailed t-tests were used with false discovery rate (FDR) correction when appropriate. RESULTS: As predicted, schizophrenia was significantly genetically correlated with any SUD excluding nicotine (R = 0.27, p = 0.033), alcohol use disorder (R = 0.35, p = 0.006), and cannabis use disorder (R = 0.24, p = 0.011). Next, using a subset of the sample that underwent structural magnetic resonance imaging (N = 506), brain structure phenotypes genetically correlated with both schizophrenia and SUD were identified. Only hippocampal volume was significantly genetically correlated with both schizophrenia (R = -0.53, p = 0.001) and any SUD (R = -0.57, p = 0.043). Furthermore, genetic effects shared between schizophrenia and SUD were significantly statistically mediated by the genetic effects on hippocampal volume. CONCLUSIONS: These findings indicate that shared genetic effects may partially explain the observed comorbidity between schizophrenia and SUD and may suggest a unique role of the hippocampus in the pathophysiology of both schizophrenia and SUD.
Perturbed sensory memory associated with schizotypy symptom load.
Torrens WA, Pablo JN, Berryhill ME … +1 more , Haigh SM
Schizophr Res · 2026 Jan · PMID 41371061 · Full text
Impaired auditory event-related potential (ERP) components, including the N100 and MMN, are linked to sensory signatures of schizophrenia. Nonclinical individuals with schizophrenia-like traits (schizotypy) provide an at...
Impaired auditory event-related potential (ERP) components, including the N100 and MMN, are linked to sensory signatures of schizophrenia. Nonclinical individuals with schizophrenia-like traits (schizotypy) provide an attractive model for investigating these ERP biomarkers, as the individuals exhibit similar traits without clinical confounds (e.g., medications). The driving theoretical framework is that there is a continuum of traits that extends from the nonclinical population to patients diagnosed with schizophrenia spectrum disorders (SSD). Here, we tested the prediction that nonclinical participants high in schizotypy traits would also exhibit impaired N100 and MMN responses, reflecting impairment in early auditory processing, and/or in predicting sensory inputs. We used a simple odd-ball pitch-deviant paradigm and compared ERP amplitudes across a sample of healthy participants who completed the Schizophrenia Personality Questionnaire - Brief Revised (SPQ-BR). Participants with high total scores (high schizotypy; N = 25) were compared to middle-scoring scorers (controls; N = 32). We then investigated more nuanced relationships between ERP components and factors of the SPQ-BR (cognitive-perceptual, interpersonal, disorganized). High schizotypy exhibited prolonged MMN latencies but intact amplitudes-a pattern also observed in those with elevated negative symptoms. However, attenuated deviant N100 amplitudes were associated with higher disorganized factor scores, whereas standard and MMN amplitudes were not. Importantly, these data suggest that early deviance detection and predictive sensory memory mechanisms are differentially perturbed with schizotypy symptom load. Further research into schizotypy traits is required to validate the population for SSD risk. In conclusion, auditory impairments can be identified in nonclinical schizotypy and leveraged to understand disorder-related processes.
Effectiveness of Integrated Neurocognitive Therapy compared to Physical Exercise and Treatment As Usual in schizophrenia: Results from a multi-center randomized controlled study.
Deste G, Barlati S, Nibbio G … +15 more , Boggian I, Cavallaro R, Giobbio GM, Poli R, Tura GB, Buonocore M, Merlin S, Malinverni G, Ossola C, Pedrini L, Scartabellati M, Ariu C, Manzin A, Vita A, CogRemSCZ Study Group
Schizophr Res · 2026 Jan · PMID 41371060 · Publisher ↗
BACKGROUND: Cognitive impairment represents one of the core features of schizophrenia, with an important negative impact of psychosocial functioning and limited pharmacological treatment options. However, psychosocial in...
BACKGROUND: Cognitive impairment represents one of the core features of schizophrenia, with an important negative impact of psychosocial functioning and limited pharmacological treatment options. However, psychosocial interventions targeting cognitive performance appear to provide significant benefits. AIMS: The aims of the present randomized controlled trial were to compare two evidence-based approaches to treat cognitive impairment and a control condition. METHODS: A total of 132 individuals diagnosed with schizophrenia were allocated to three treatment arms: a Cognitive Remediation intervention (Integrated Neurocognitive Therapy - INT, n = 53), Physical Exercise (PE, n = 37), and Treatment As Usual (TAU, n = 42) and assessed at the beginning and at the conclusion of the treatment period (15 weeks) with measures of symptoms severity, cognitive performance, and psychosocial functioning. RESULTS: Significant between-groups post-treatment effects were observed for Executive Functions, Social Cognition, and Global Cognitive Performance. Post-hoc analyses showed the superiority of INT over TAU on Executive Functions and Global Cognitive Performance. The superiority of INT over PE in Executive Functions and Social Cognition also emerged in the post-hoc analyses. No significant between-groups differences were observed regarding symptoms severity and functional outcomes. CONCLUSIONS: The results of this study confirm the effectiveness of cognitive rehabilitation, and in particular of INT as an evidence-based treatment for outpatients diagnosed with schizophrenia. Even though the effects on the outcomes in this study observed for PE were not statistically significant, the PE intervention might represent a valid approach in rehabilitation settings.
Distinct neuroimaging signatures of OSSO compared to schizophrenia and healthy controls using graph theoretical analysis.
Odkhuu S, Kim WS, Li L … +5 more , Setiani A, Le TH, Rami FZ, Nazir S, Chung YC
Schizophr Res · 2026 Jan · PMID 41365234 · Publisher ↗
BACKGROUND: This study examined topological features and network resilience in schizophrenia spectrum disorders (SSDs), other specified schizophrenia spectrum and other psychotic disorder (OSSO), and healthy controls (HC...
BACKGROUND: This study examined topological features and network resilience in schizophrenia spectrum disorders (SSDs), other specified schizophrenia spectrum and other psychotic disorder (OSSO), and healthy controls (HC) with resting-state functional MRI (rs-fMRI) and graph theoretical analysis. Associations between topological metrics, resilience, and symptom severity were also explored. METHODS: rs-fMRI data from SSDs (n = 77), OSSO (n = 86), and HC (n = 83) were analyzed for global efficiency (Eg), characteristic path length (Lp), nodal local efficiency (NLe), nodal clustering coefficient (NCp), and resilience derived from k-shell decomposition and targeted-attack simulations. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Both patient groups showed reduced Eg and increased Lp compared with HC, indicating disrupted global integration. At the nodal level, the fusiform gyrus exhibited decreased NLe and NCp in both groups. In OSSO, these nodal metrics correlated with PANSS general and total scores. SSDs displayed pronounced reductions in k-core and maximum-core resilience, whereas OSSO largely retained network stability. k-Shell resilience was most impaired in SSDs, with OSSO showing intermediate deficits. Notably, k-shell resilience in the right superior occipital gyrus significantly differed between OSSO and SSDs. CONCLUSION: This study presents the first investigation of OSSO-specific neuroimaging signatures using network resilience analysis. OSSO showed partial preservation of k-core resilience and intermediate k-shell resilience between SSDs and HC, suggesting distinct neurobiological organization within the psychosis spectrum. k-Shell resilience in the superior occipital gyrus may serve as a potential neuroimaging marker distinguishing OSSO from SSDs.
Fracture risk in the offspring of individuals with schizophrenia: A cohort study of 71,698 children.
Wang SC, Hsu JW, Tsai SJ … +5 more , Bai YM, Su TP, Chen TJ, Huang WS, Chen MH
Schizophr Res · 2026 Jan · PMID 41349381 · Publisher ↗
BACKGROUND: Parental schizophrenia is associated with various adverse developmental outcomes in offspring, including neurodevelopmental impairments and elevated physical injury risks. However, limited evidence is availab...
BACKGROUND: Parental schizophrenia is associated with various adverse developmental outcomes in offspring, including neurodevelopmental impairments and elevated physical injury risks. However, limited evidence is available regarding the association between parental schizophrenia and fracture risk in offspring, particularly during adolescence-a developmental stage characterized by increased susceptibility to fractures. In this study, we investigated whether parental schizophrenia influences the risk of fractures in offspring. METHODS: Relevant data were collected from Taiwan's National Health Insurance Research Database. This retrospective cohort study included 6518 offspring of individuals with schizophrenia and 65,180 age- and sex-matched children whose parents had no severe mental disorders. The cohort was followed from 1996 or birth until the end of 2011. Incident fractures during this period were identified. Cox proportional-hazards models, adjusted for demographic characteristics and psychiatric comorbidities in offspring, were used to estimate hazard ratios (HRs) and corresponding 95 % confidence intervals (CIs) for fracture risk. RESULTS: Compared with the offspring of individuals without schizophrenia, those of individuals with this condition had significantly increased risks of any fractures (HR: 1.10; 95 % CI: 1.03-1.18), skull fractures (HR: 1.38; 95 % CI: 1.13-1.68), lower limb fractures (HR: 1.15; 95 % CI: 1.03-1.28), and severe fractures requiring hospitalization (HR: 1.20; 95 % CI: 1.08-1.34). The increased fracture risk was particularly pronounced during adolescence (HR: 1.14; 95 % CI: 1.03-1.26). CONCLUSION: The offspring of individuals with schizophrenia have an increased risk of fractures, particularly during adolescence. Early screening and targeted preventive strategies-including interventions for attention regulation and motor skill difficulties-are needed to reduce fracture risk in this vulnerable population.
Fidelity to the first episode psychosis coordinated specialty care model in Massachusetts: Comparison to clinical outcomes and national programs.
DeTore NR, Johnson K, Eberlin ES … +8 more , Imam I, Saluja A, Guyer M, Keshavan M, Öngür D, Mueser KT, Addington D, MAPNET/LEAP Consortium
Schizophr Res · 2026 Jan · PMID 41289928 · Full text
Measuring fidelity to the components of the coordinated specialty care (CSC) model is a critical step in understanding the success of first episode of psychosis (FEP) programs. This study assessed the fidelity of nine Ma...
Measuring fidelity to the components of the coordinated specialty care (CSC) model is a critical step in understanding the success of first episode of psychosis (FEP) programs. This study assessed the fidelity of nine Massachusetts CSC programs on a well-validated fidelity measure (the FEP Services Fidelity Scale: FEPS-FS 1.1) and a locally adapted measure (the Massachusetts Psychosis Fidelity Scale: MAPS). Associations between the two fidelity measures were examined, and correlations between fidelity and change in clinical outcomes on the Massachusetts Psychosis Network for Early Treatment assessment battery were explored within 684 clients served through these sites. Overall fidelity of the Massachusetts CSC program with programs in a national study of CSC were also compared on the FEPS-FS. Several fidelity items (weekly team meetings, quick contact with referred clients, and procedural and structural aspects of programs) were related with clinical outcomes, including fewer emergency department visits within the first six months of treatment and client satisfaction at six months (ps < 0.027). Overall CSC fidelity in Massachusetts was significantly higher than the national average (p < .001) and fidelity did not differ between academically and non-academically affiliated sites. The Massachusetts FEP programs had strong fidelity to the CSC model components, higher than national rates. Findings indicate that stronger fidelity may support relapse prevention, as higher fidelity in several key components was related to fewer emergency department visits. This study also highlights the utility of both a thoroughly researched and universal measure of CSC fidelity along with the importance of local adaptations to the measure.
Association between decreased peripheral serum complement C3 levels and aberrant brain topology of morphological similarity networks in first-episode, drug-naïve schizophrenia.
Zhang K, Xia X, Dai J … +19 more , Deng Z, Kang S, Hong Z, Li Z, Wu J, Chen C, Qiu Y, Liu T, Chen M, Ma J, Liu Y, Zhang Z, Shen Q, Tao S, Pan Y, Zhu F, Kang Z, Zou Y, Wei Q
Schizophr Res · 2026 Jan · PMID 41274180 · Publisher ↗
BACKGROUND: Previous studies have highlighted the critical role of the complement system in schizophrenia. Dysregulated levels of complement C3 and C4 may affect structural brain networks in schizophrenia, yet their rela...
BACKGROUND: Previous studies have highlighted the critical role of the complement system in schizophrenia. Dysregulated levels of complement C3 and C4 may affect structural brain networks in schizophrenia, yet their relationship remains unclear. This study aimed to explore the association between peripheral serum levels of complement and the topological properties of individualized morphological similarity networks (MSNs) in first-episode, drug-naïve schizophrenia (FES). METHODS: This study included 71 patients with FES and 92 healthy controls (HCs). Peripheral blood samples were collected to quantify C3 and C4 levels. Individualized MSNs were constructed for each participant separately based on cortical thickness (CT), gray matter volume (GMV), and surface area (SA), and then graph theoretical analysis was applied to compute topological properties. Group comparisons were performed on complement levels and MSN topological properties, followed by correlation analyses between altered measures. RESULTS: Compared to HCs, FES patients exhibited decreased C3 levels, with no significant difference in C4 levels. The FES group showed significantly lower clustering coefficient (C) than HCs. Nodal properties were altered in FES patients, characterized by decreased degree centrality and nodal efficiency in the left superior temporal sulcus and increased nodal efficiency in the left temporal pole for the CT-based networks. Moreover, within the FES group and the overall cohort, C3 levels were positively correlated with the C of MSNs. CONCLUSIONS: The present study confirmed that decreased C3 levels are associated with the C of MSNs. Our findings suggest that the complement system may contribute to morphological network disruptions in FES.
Effects of disease duration and antipsychotics on brain age in schizophrenia.
Roig-Herrero A, San-José-Revuelta LM, Navarro-González R … +2 more , de Luis-García R, Molina V
Schizophr Res · 2026 Jan · PMID 41274179 · Publisher ↗
Accelerated brain aging has been consistently reported in patients with schizophrenia. Over the past decade, these findings have been replicated using the Brain Age paradigm, which applies machine learning techniques to...
Accelerated brain aging has been consistently reported in patients with schizophrenia. Over the past decade, these findings have been replicated using the Brain Age paradigm, which applies machine learning techniques to estimate brain age from neuroimaging data. This approach yields a single index, the Brain Age Gap, defined as the difference between predicted and chronological age. Nevertheless, both the progressive nature of this phenomenon and the potential role of antipsychotic medication remain unclear. To investigate its progression, we compared the Brain Age Gap between individuals experiencing a first episode of psychosis and healthy controls using ANCOVA, adjusting for age, sex, body mass index, and estimated total intracranial volume. To enhance the robustness of our findings, we employed two distinct models: a transformer-inspired model based on harmonized volumetric brain features extracted with FastSurfer, and a previously trained deep learning model. To assess the potential effect of medication, we further compared bipolar patients who received antipsychotic treatment with those who did not. Mann-Whitney U test consistently showed that medicated bipolar patients did not exhibit a significantly larger Brain Age Gap. Both models converge on the conclusion that accelerated brain aging is unlikely to be explained by antipsychotic medication alone. Longitudinal studies are therefore required to clarify the temporal dynamics of brain aging in schizophrenia.
Epidemiological analysis of schizophrenia and incarceration: A multi-center exploration of the criminalization of mental illness in the United States.
Das N, Dhamija R, Mistak D … +5 more , Diaz LD, Kaelber DC, Mulloy K, Malhotra T, Maier V
Schizophr Res · 2026 Jan · PMID 41270399 · Full text
OBJECTIVE: This study investigates the diagnostic relationship between schizophrenia and incarceration and elucidates a temporal relationship between these conditions. METHODS: This analysis utilized TriNetX (December 20...
OBJECTIVE: This study investigates the diagnostic relationship between schizophrenia and incarceration and elucidates a temporal relationship between these conditions. METHODS: This analysis utilized TriNetX (December 2024), querying 60+ U.S. Healthcare Organizations using ICD-10-CM codes to compare the prevalence ratio (PR) of schizophrenia in patients with and without electronic health record (EHR) documented incarceration, and conversely, to compare the PR of incarceration in patients with and without schizophrenia. An additional cumulative incidence ratio (CIR) analysis was performed to compare cumulative incidence of incarceration after schizophrenia diagnosis to that of incarceration before diagnosis. RESULTS: Of 80,224 patients with incarceration history, 7.35 % had schizophrenia, compared to 0.36 % among those without incarceration (PR: 20.3, 95 % C.I. 19.8-20.8). Of 423,270 people with schizophrenia, 1.4 % had incarceration history compared to 0.06 % among people without schizophrenia (PR: 21.6, 95 % C.I. 21.0-22.1). Schizophrenia followed incarceration in 1.5 % of cases, while incarceration followed schizophrenia in 0.93 % (CIR: 0.62 %, 95 % C.I. 0.53-0.71 %). CONCLUSIONS: Schizophrenia is overrepresented in incarcerated populations, and incarceration may be a risk factor for schizophrenia presentation. Adopting a medicalized approach to criminal justice may help alleviate the U.S.'s mass incarceration crisis.
Estimating the relative efficacy of xanomeline/trospium from placebo-controlled trials.
Majkic N, Taylor D
Schizophr Res · 2026 Jan · PMID 41270398 · Publisher ↗
Abstract loading — click title to view on PubMed.
Does insight improve during the course of psychosis?
Seif P, Del Re EC, Tamminga CA … +9 more , Pearlson GD, Clementz BA, McDowell J, Ivleva EI, Hamada K, Hill S, Keedy SK, Gershon ES, Keshavan M
Schizophr Res · 2026 Jan · PMID 41270397 · Publisher ↗
INTRODUCTION: Insight, awareness of illness, is often impaired in psychotic disorders and relates to symptom severity and cognition, but its association with time since first diagnosis is unclear. We examined insight, co...
INTRODUCTION: Insight, awareness of illness, is often impaired in psychotic disorders and relates to symptom severity and cognition, but its association with time since first diagnosis is unclear. We examined insight, cognition, and time since first diagnosis in a large multi-diagnostic sample. METHODS: We studied patients with schizophrenia (SZ, n = 957), schizoaffective disorder (SAD, n = 723) and bipolar I disorder with psychotic features (BP, n = 691). Cognitive function was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS) battery. Insight was measured using item G12 from the Positive and Negative Syndrome Scale (PANSS), where higher scores indicate poorer insight. RESULTS: Insight differed by diagnosis (p < .001), poorest in SZ vs SAD and BP. Within SZ, first-year cases had higher PANSS-G12 than those ≥3 years from first diagnosis (p < .01). Hierarchical regressions showed diagnosis and symptom severity explained most variance in insight; cognition added only a small increment. In SZ, insight was modestly inversely related to time since first diagnosis (ρ = -0.124, p = .001) and weakly to cognition (ρ = -0.084, p = .029). Poorer insight correlated with more severe negative (ρ = 0.259, p < .001) and positive symptoms (ρ = 0.347, p < .001). No associations with time since diagnosis or cognition were seen in SAD or BP. CONCLUSION: In SZ, insight showed a statistically significant but very small cross-sectional association with longer time since first diagnosis (better insight with longer duration), with the largest deficit in the first year. Early, diagnosis-tailored psychoeducation and metacognition-focused supports may help support gains in insight and engagement.
Cannabis use and cardiometabolic risk in schizophrenia.
Paris J, Laurendi O, Arnet V … +1 more , Galletly C
Schizophr Res · 2026 Jan · PMID 41265115 · Publisher ↗
PURPOSE: Metabolic syndrome (MetS) is common in schizophrenia and drives cardiovascular risk. While cannabis use and potency are increasing, the impact of cannabis on cardiometabolic health in schizophrenia remains uncle...
PURPOSE: Metabolic syndrome (MetS) is common in schizophrenia and drives cardiovascular risk. While cannabis use and potency are increasing, the impact of cannabis on cardiometabolic health in schizophrenia remains unclear. This study assessed the association between objectively measured cannabis use and MetS prevalence in a large schizophrenia cohort. METHODS: We conducted a cross-sectional analysis of 988 participants with DSM-IV schizophrenia from the CATIE study. Cannabis use was measured via hair testing for tetrahydrocannabinol (THC), the gold standard for long-term use detection. MetS was defined per International Diabetes Federation criteria using physical and biochemical data. Multivariable logistic regression, adjusting for demographic, clinical, and lifestyle confounders, assessed the association between THC use and MetS. RESULTS: THC-positive participants (14.8 %) exhibited a significantly lower prevalence of MetS compared to non-users (42.5 % vs. 60.5 %, p < 0.001). After adjusting for confounders including age, sex, ethnicity, smoking, and other substance use, cannabis use remained independently associated with reduced odds of MetS (adjusted OR 0.64, 95 %CI 0.44-0.93, p = 0.02). Among MetS components, cannabis users had significantly lower odds of elevated waist circumference after adjustment (adjusted OR 0.61, 95 %CI 0.41-0.91, p = 0.02). Cannabis use was also associated with lower weight, BMI and triglycerides and higher HDL in unadjusted analyses. No significant differences were found in blood pressure or fasting glucose. CONCLUSIONS: In schizophrenia, cannabis use was associated with lower rates of both metabolic syndrome and central obesity. While these findings support emerging evidence of metabolic differences in cannabis users, the cross-sectional design precludes conclusions regarding causality. Longitudinal studies are needed to clarify long-term metabolic effects and guide targeted interventions.
The challenges in measuring symptoms of schizophrenia: An exploratory graph analysis of the Positive and Negative Syndrome Scale (PANSS).
Serafim PHM, Gadelha A, Massuda R … +5 more , Louzã M, Gama CS, Roguski LCO, Alvim PHP, Czepielewski LS
Schizophr Res · 2026 Jan · PMID 41253020 · Publisher ↗
BACKGROUND AND HYPOTHESIS: The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for assessing symptom severity in schizophrenia. Significant concerns remain regarding its structural validity, with...
BACKGROUND AND HYPOTHESIS: The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for assessing symptom severity in schizophrenia. Significant concerns remain regarding its structural validity, with no consensus on a definitive model. Although the five-factor model (positive, negative, cognitive, hostility, and affective) is the most widely accepted, studies have demonstrated instability in item distribution across factors and difficulty in achieving adequate fit indices. This exploratory study aims to evaluate the structural validity of the PANSS, addressing these previously identified issues and contributing to the theoretical debate on the limited evidence supporting a robust model fit. STUDY DESIGN: Data from five independent Brazilian samples (N = 1262) were analyzed. We conducted Exploratory Graph Analysis (EGA) and bootstrap analysis to assess the stability of the PANSS structure. We estimated network loadings and conducted the Loadings Comparison Test (LCT) to evaluate differences between structural frameworks. STUDY RESULTS: The analysis identified a five-dimensional model consistent with prior literature. However, this model proved unstable, appearing in only 66.3 % of bootstrap samples. Several items exhibited low stability across dimensions, and the LCT algorithm indicated that a network framework provided a better fit for the data. CONCLUSIONS: In line with previous research, this study found that the PANSS exhibits an unstable structure and item distribution. Moreover, the scale presents several validity limitations, and the difficulty in achieving a consolidated model may reflect both methodological gaps in its original construction and the inherently multidimensional nature of certain symptoms.
Spatio-temporal information transition abnormalities across brain functional networks in early-onset schizophrenia.
Fan YS, Ye M, Xu Y … +5 more , Xu Y, Guo J, Yang M, Huang W, Chen H
Schizophr Res · 2026 Jan · PMID 41253019 · Publisher ↗
Schizophrenia is a complex neurodevelopmental disorder characterized by widespread functional dysconnectivities across the brain. While disturbed temporal dynamics have been reported in schizophrenia, the information flo...
Schizophrenia is a complex neurodevelopmental disorder characterized by widespread functional dysconnectivities across the brain. While disturbed temporal dynamics have been reported in schizophrenia, the information flow involving both temporal and spatial dynamics remains unclear. To capture spatio-temporal transition of brain information and to investigate these processes from a neurodevelopmental perspective, we collected resting-state functional MRI (rs-fMRI) data from 86 early-onset schizophrenia (EOS) patients (onset before age 18) and 91 demographically matched typically developing (TD) controls. We employed a non-homogeneous Markov model (NHMM) on dynamic functional connectivities derived from fMRI data. By means of transition probabilities, we modeled the switching of information flow in brain functional networks over time. Stationary probability vectors were used to describe the information convergence distribution of each network, while optimal reachable steps were used to characterize inter-network transmission efficiency. Compared to controls, EOS patients showed significantly increased stationary transition probabilities in the ventral attention network (VAN) and the dorsal attention network (DAN) but decreased probabilities in the default mode network (DMN). In terms of the dynamic interaction characteristics between networks, patients showed increased optimal reachable steps relative to controls, particularly in the VAN-DMN pathway. By integrating NHMM with neuroimaging data, this study revealed VAN- and DMN-involved information transition abnormalities in the early stage of schizophrenia spatio-temporal dynamics, offering novel insights into the developmental pathophysiology of the disorder. Our approach thus provides a novel analytical framework for quantifying spatio-temporal brain dynamics in neurodevelopmental disorders.
Unveiling the prognosis of adult Catatonia: A systematic review.
Rodriguez-Cabo B, Catalan A, Aymerich C … +2 more , Salazar de Pablo G, Gonzalez-Torres MA
Schizophr Res · 2026 Jan · PMID 41253018 · Publisher ↗
INTRODUCTION: Catatonia is a neuropsychiatric syndrome observed in psychiatric and physical conditions. Linked to neuroinflammation, schizophrenia spectrum disorders remain its principal diagnostic context. Short-term ou...
INTRODUCTION: Catatonia is a neuropsychiatric syndrome observed in psychiatric and physical conditions. Linked to neuroinflammation, schizophrenia spectrum disorders remain its principal diagnostic context. Short-term outcomes are favourable with prompt treatment. Long-term prognosis remains poorly understood. This systematic review aimed to evaluate long-term outcomes and mortality rates in individuals with catatonia. METHODS: We conducted a PRISMA-compliant systematic review (PROSPERO: CRD420251027945) searching PubMed, Web of Science, EMBASE, SCOPUS, PsycINFO, and non-peer-reviewed sources from database inception to July 12, 2025. We included studies of adults diagnosed with catatonia with a minimum 6-month follow-up. Catatonia diagnosis was based on criteria, scales, or clinical judgment. One-year mortality was estimated and compared to general population. Methodological quality was assessed using validated tools (NOS, JBI). Findings were synthesized narratively. RESULTS: Of 6431 records screened, 29 studies met inclusion criteria, encompassing 30,694 patients with catatonia and 11,830 controls. Mean follow-up was 8.1 years. Seventeen studies focused on schizophrenia. Quality of studies was heterogeneous; 58 % showed moderate concerns and 41 % were at high risk of bias. Post-1970s studies reported more episodes, readmissions, and chronicity in catatonic schizophrenia versus other schizophrenia subtypes. Poorer psychiatric outcomes were found when catatonia co-occurred with intellectual disability, depression, or physical illness. Catatonia associated with baseline suicidal ideation (>35 % patients) and follow-up autoimmunity. In 75 % of post-1970s studies, one-year mortality in catatonia cohorts was lower than adjusted population rates. CONCLUSION: Catatonia is a marker of poor psychiatric long-term prognosis, without clear link to higher mortality. Early use of effective treatments preventing suicide or psychosis relapses may be considered.
The hippocampal-cortical system cerebral blood flow in schizophrenia: Primary disease versus antipsychotic medication effects.
Ciarolla A, Bobilev AM, Dybowski F … +8 more , Fang Y, Sacco C, Palka JM, Aslan S, Liu P, Lu H, Tamminga CA, Ivleva EI
Schizophr Res · 2026 Jan · PMID 41240458 · Full text
Most of the brain-based biomarker research in schizophrenia (SZ) results from chronic medicated samples. Disambiguating contributions of "primary" disease vs. psychotropic medication effects to the neurobiology of SZ rem...
Most of the brain-based biomarker research in schizophrenia (SZ) results from chronic medicated samples. Disambiguating contributions of "primary" disease vs. psychotropic medication effects to the neurobiology of SZ remains challenging. In this study, using 3Tesla pseudo-continuous Arterial Spin Labeling (pCASL), we examined regional cerebral blood flow (CBF) in hippocampus and its cortical projection network in SZ probands [n = 41, including antipsychotic-free (SZ-OFF, n = 14) and treated with antipsychotic(s) (SZ-ON, n = 27)], their first-degree relatives [n = 28, including relatives with lifetime psychosis-spectrum disorders (REL-P, n = 14) and without (REL-NP, n = 14)], and healthy controls (HC, n = 16) [n = 85 total]. SZ-OFF demonstrated elevated CBF in the left middle cingulate, ventromedial and dorsolateral prefrontal cortex (PFC), compared to SZ-ON (Hedges' g = 0.65-0.91). No difference in hippocampal CBF emerged in SZ-OFF vs. SZ-ON, while SZ-OFF vs. HC showed reduced CBF in the left anterior hippocampus (g = 1.09). Among relatives, REL-P had elevated CBF in the right ventrolateral PFC, compared to REL-NP (g = 0.73) - resembling the "hyperfrontality" effect in SZ-OFF. Conversely, REL-NP vs. HC showed reduced CBF throughout the right PFC (g = 0.52-0.79). Our findings demonstrate unique regional CBF-based activity signatures potentially capturing primary disease effects (SZ-OFF: elevated CBF in PFC but reduced CBF in the anterior hippocampus) vs. antipsychotic effects (SZ-ON: "normalization" of CBF). The observed PFC "hyperactivity" (evidenced by elevated CBF in both SZ-OFF and REL-P) may constitute a regionally-specific "psychosis maker". Future research targeted at granular aspects of hippocampal-PFC pathology in medicated and unmedicated samples may inform more precise, novel interventions in SZ.
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