No studies have investigated the effects of virtual reality (VR) on the persecutory idea of reference (IOR) or delusions of reference (DOR) in patients with psychosis. This study examined the efficacy and safety of VR therapy in stable outpatients with psychosis and explored relationships between primary outcomes and psychological factors using path analysis.

Seventy-eight patients were randomly assigned to either the VR-treatment (VR-T) or VR-control (VR-C) group. The VR-T group viewed three 360° 3D videos or four animated videos; the VR-C group viewed the same seven videos with muted voices or 11 360° 3D videos of natural scenes. Pre- and post-assessments were performed using the Psychotic Symptom Rating Scale-Delusions (PSYRATS-D) and Revised Green et al. Paranoid Thought Scale (R-GPTS) as a primary outcome measure. Several self-rating scales measuring schema, depression, brooding, negative evaluation, attribution bias, and self-esteem were administered. Safety was assessed after sessions 1 and 10, and path models were constructed.

Between-group analysis showed a significant improvement in PSYRATS-D scores in the VR-T group compared with the VR-C group. Regarding self-rating scales, the between-group analysis revealed a significant group × time interaction only for the Social and Occupational Functioning Assessment Scale (SOFAS) score. The frequency of VR sickness was high, but its severity was mild. Fear of Negative Evaluation Scale and Beck Depression Inventory scores were found to have mediating roles.

VR therapy effectively reduced delusions in young, stable psychosis patients with mild and tolerable side effects. Future studies should develop diverse VR content for older populations.

Mindfulness is a promising psychological resource that can alleviate dysfunctional fear responses and promote mental health. We investigated how mindfulness affects fear and depression in isolated patients with coronavirus disease 2019 (COVID-19), and whether it acts as a mediator.

We conducted an online survey of COVID-19 patients undergoing at-home treatment from February to April 2022. The survey included a questionnaire on fear of COVID-19 (measured by the Fear of COVID-19 Scale), mindfulness (measured by the Mindful Attention Awareness Scale), and depression (measured by the Patient Health Questionnaire). A total of 380 participants completed the questionnaire. We analyzed the correlation between each variable and performed a mediation analysis using hierarchical regression and bootstrapping to verify the statistical significance of the mediating effects.

Each variable was significantly correlated. Hierarchical regression analysis showed that the association between the fear of COVID-19 and depression decreased from 0.377-0.255, suggesting that mindfulness partially mediates the relationship between fear of COVID-19 and depression. Bootstrapping analysis showed that the indirect effect of the mediating variable (mindfulness) is 0.121, which accounts for 32.3% of the total effect.

Interventions that promote mindfulness in patients with acute COVID-19 may be beneficial for their mental health.

Emerging evidence indicates that gene–environment interactions (GEIs) are important underlying mechanisms for the development of schizophrenia (SZ). We investigated the associations of polygenic risk score for SZ (PRS-SZ), environmental measures, and their interactions with case–control status and clinical phenotypes among patients with schizophrenia spectrum disorders (SSDs).

The PRS-SZ for 717 SSD patients and 356 healthy controls (HCs) were calculated using the LDpred model. The Korea-Polyenvironmental Risk Score-I (K-PERS-I) and Early Trauma Inventory-Self Report (ETI-SR) were utilized as environmental measures. Logistic and linear regression analyses were performed to identify the associations of PRS-SZ and two environmental measures with case–control status and clinical phenotypes.

The PRS-SZ explained 8.7% of SZ risk. We found greater associations of PRS-SZ and total scores of the K-PERS-I with case–control status compared to the ETI-SR total score. A significant additive interaction was found between PRS-SZ and K-PERS-I. With the subdomains of the K-PERS-I and ETI-SR, we identified significant multiplicative or additive interactions of PRS-SZ and parental socioeconomic status (pSES), childhood adversity, and recent life events in association with case–control status. For clinical phenotypes, significant interactions were observed between PRS-SZ and the ETI-SR total score for negative-self and between PRS-SZ and obstetric complications within the K-PERS-I for negative-others.

Our findings suggest that the use of aggregate scores for genetic and environmental measures, PRS-SZ and K-PERS-I, can more accurately predict case–control status, and specific environmental measures may be more suitable for the exploration of GEIs.

Patients with schizophrenia experience accelerated aging, accompanied by abnormalities in biomarkers such as shorter telomere length. Brain age prediction using neuroimaging data has gained attention in schizophrenia research, with consistently reported increases in brain-predicted age difference (brain-PAD). However, its associations with clinical symptoms and illness duration remain unclear.

We developed brain age prediction models using structural magnetic resonance imaging (MRI) data from 10,938 healthy individuals. The models were validated on an independent test dataset comprising 79 healthy controls, 57 patients with recent-onset schizophrenia, and 71 patients with chronic schizophrenia. Group comparisons and the clinical associations of brain-PAD were analyzed using multiple linear regression. SHapley Additive exPlanations (SHAP) values estimated feature contributions to the model, and between-group differences in SHAP values and group-by-SHAP value interactions were also examined.

Patients with recent-onset schizophrenia and chronic schizophrenia exhibited increased brain-PAD values of 1.2 and 0.9 years, respectively. Between-group differences in SHAP values were identified in the right lateral prefrontal area (false discovery rate [FDR] p = 0.022), with group-by-SHAP value interactions observed in the left prefrontal area (FDR p = 0.049). A negative association between brain-PAD and Full-scale Intelligence Quotient scores in chronic schizophrenia was noted, which did not remain significant after correction for multiple comparisons.

Brain-PAD increases were pronounced in the early phase of schizophrenia. Regional brain abnormalities contributing to brain-PAD likely vary with illness duration. Future longitudinal studies are required to overcome limitations related to sample size, heterogeneity, and the cross-sectional design of this study.

Comorbid depression substantially affects the management of glycemia and diabetes-related complications among patients with type 2 diabetes mellitus. In this study, we sought to determine the association between weight change over 4 years and depression risk among patients with type 2 diabetes mellitus.

This population-based retrospective cohort study from the National Health Insurance Services of Korea included 1 111 345 patients with type 2 diabetes who were divided into groups according to body weight change over 4 years. Body weight changes were compared with the preceding 4-year period (2005–2008). Depression was defined according to the International Classification of Diseases 10th revision code for depression (F32 and F33) on one or more inpatient or outpatient claims.

During a median follow-up of 7.4 years, 244 081 cases of depression were identified. We observed a U-shaped association between body weight change and depression risk with a higher risk among both groups of weight loss (hazard ratio (HR) 1.17, 95% CI 1.15–1.19 for ⩾ −10%; HR 1.07, 95% CI 1.06–1.08 for −10 to −5%) and weight gain (HR 1.06, 95% CI 1.04–1.08 for ⩾10%; HR 1.02, 95% CI 1.01–1.04 for 5–10%) compared with the stable weight group (−5 to 5%).

A U-shaped association between body weight change and depression risk was observed in this large nationwide cohort study. Our study suggests that patients with type 2 diabetes and weight change, either gain or loss, could be considered a high-risk group for depression.

Many previous studies have shown that the APOE e4 genotype affects cognition, brain volume, glucose metabolism and amyloid deposition. However, these studies were conducted separately, and few studies simultaneously investigated the effects of the APOE e4 genotype on cognition, brain volume, glucose metabolism and amyloid deposition in Alzheimer disease (AD). The purpose of this study is to simultaneously investigate the association of the APOE e4 genotype with cognition, brain volume, glucose metabolism and amyloid deposition in patients with AD.

This is a cross-sectional study of 69 subjects with Alzheimer’s disease (AD). All subjects were divided into carriers and noncarriers of the ε4 allele. Forty APOE ε4 carriers and 29 APOE ε4 non-carriers underwent neuropsychological, structural magnetic resonance imaging, 18F-fluorodeoxyglucose positron emission tomography scans (18F-FDG-PET) and 18F-Florbetaben amyloid positron emission tomography scans (amyloid PET). Analysis of covariance (ANCOVA) was conducted to compare the differences on cognition, brain volume, glucose metabolism and amyloid deposition between APOE ε4 carriers and non-carriers after controlling demographics.

APOE ε4 carriers had 50% lower scores of SVLT_delayed recall compared to non-carriers (0.88 ± 1.65 vs 1.76 ± 1.75). However, APOE ε4 carriers performed better on other cognitive tests than non- carriers (K-BNT (11.04 ± 2.55 vs 9.66 ± 2.82), RCFT (25.73 ± 8.56 vs 20.15 ± 10.82), and Stroop test_color response (48.28 ± 26.33 vs 31.56 ± 27.03)). APOE ε4 carriers had slightly smaller hippocampal volume than non-carriers (3.09 ± 0.38 vs 3.32 ± 0.38), but greater total brain cortical thickness (1.45 ± 1.55 vs 1.37 ± 1.24).

We found that APOE e4 genotype is associated with cognition, brain volume in AD, suggesting that APOE e4 genotype can play a very important role in the underlying pathogenesis of AD.

Previous studies investigating neuropsychological profiles of cognitive impairment people have found a learning curve can be a useful indicator of AD diagnosis or progression. However, the data on the relationship between amyloid β (Aβ) deposition status and the learning curve in amnestic mild cognitive impairment (aMCI) are limited. In this study, we investigate the role of the learning curve in predicting Aβ deposition status in patients with aMCI.

This is a cross-sectional study of 67 aMCI patients (N = 67; 33 aMCI with amyloid positive (Aβ-PET (+)), and 34 aMCI with amyloid negative (Aβ-PET (-))). All participants underwent Seoul Neuropsychological Screening Battery for a comprehensive neuropsychological test battery and brain MRI. To determine Aβ deposition status, each participant underwent amyloid PET scans using 18F-florbetaben. The learning curve was obtained using immediate recall of Seoul Verbal Learning Test-learning curve (SVLT- learning curve). The association of cognitive test scores and dichotomized Aβ deposition status was examined using logistic regression models in patients with aMCI. Receiver operating characteristic (ROC) curves were used to examine the predictive ability of cognitive test to detect Aβ deposition status in aMCI.

Logistic regression models showed that SVLT-learning curve and Rey Complex Figure Test- delayed recall (RCFT-delayed recall) scores were significantly associated with Aβ deposition status. In ROC analysis to assess the predictive power, SVLT-learning curve (area under the curve (AUC) = 0.734, P = 0.001) and RCFT-delayed recall (AUC = 0.739, P = 0.001) independently discriminated Aβ-PET (+) and Aβ-PET (-). The combination of these clinical markers (SVLT-learning curve and RCFT-delayed recall) improved the predictive accuracy of Aβ-PET (+) (AUC = 0.833, P < 0.001).

Our findings of association of Aβ deposition status with SVLT-learning curve and RCFT- delayed recall suggest that these cognitive tests could be a useful screening tool for Aβ deposition status among aMCI patients in resource-limited clinics.