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.

Substantial evidence indicates structural abnormalities in the cerebral cortex of patients with schizophrenia (SCZ), although their clinical implications remain unclear. Previous case-control studies have investigated group-level differences in structural abnormalities, although the study design cannot account for interindividual differences. Recent research has focused on the association between the heterogeneity of the cerebral cortex morphometric features and clinical heterogeneity.

We used neuroimaging data from 420 healthy controls and 695 patients with SCZ from seven studies. Four cerebral cortex measures were obtained: surface area, gray matter volume, thickness, and local gyrification index. We calculated the coefficient of variation (CV) and person-based similarity index (PBSI) scores and performed group comparisons. Associations between the PBSI scores and cognitive functions were evaluated using Spearman's rho test and normative modeling.

Patients with SCZ had a greater CV of surface area and cortical thickness than those of healthy controls. All PBSI scores across cortical measures were lower in patients with SCZ than in HCs. In the patient group, the PBSI scores for gray matter volume and all cortical measures taken together positively correlated with the full-scale IQ scores. Patients with deviant PBSI scores for gray matter volume and all cortical measures taken together had lower full-scale IQ scores than those of other patients.

The cerebral cortex in patients with SCZ showed greater regional and global structural variability than that in healthy controls. Patients with deviant similarity of cortical structural profiles exhibited a lower general intelligence than those exhibited by the other patients.

Predicting the course of depression is necessary for personalized treatment. Impaired glucose metabolism (IGM) was introduced as a promising depression biomarker, but no consensus was made. This study aimed to predict IGM at the time of depression diagnosis and examine the relationship between long-term prognosis and predicted results.

Clinical data were extracted from four electronic health records in South Korea. The study population included patients with depression, and the outcome was IGM within 1 year. One database was used to develop the model using three algorithms. External validation was performed using the best algorithm across the three databases. The area under the curve (AUC) was calculated to determine the model’s performance. Kaplan–Meier and Cox survival analyses of the risk of hospitalization for depression as the long-term outcome were performed. A meta-analysis of the long-term outcome was performed across the four databases.

A prediction model was developed using the data of 3,668 people, with an AUC of 0.781 with least absolute shrinkage and selection operator (LASSO) logistic regression. In the external validation, the AUCs were 0.643, 0.610, and 0.515. Through the predicted results, survival analysis and meta-analysis were performed; the hazard ratios of risk of hospitalization for depression in patients predicted to have IGM was 1.20 (95% confidence interval [CI] 1.02–1.41, p = 0.027) at a 3-year follow-up.

We developed prediction models for IGM occurrence within a year. The predicted results were related to the long-term prognosis of depression, presenting as a promising IGM biomarker related to the prognosis of depression.

It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries.

This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors.

A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5–19.5) in Japan, 23.0 days (95% CI 19.9–26.1) in Korea, and 15.0 days (95% CI 13.0–17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01–1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00–1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77–1.35; p = 0.89).

SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.

Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.

PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.

Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.

These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

Network approach has been applied to a wide variety of psychiatric disorders. The aim of the present study was to identify network structures of remitters and non-remitters in patients with first-episode psychosis (FEP) at baseline and the 6-month follow-up.

Participants (n = 252) from the Korean Early Psychosis Study (KEPS) were enrolled. They were classified as remitters or non-remitters using Andreasen's criteria. We estimated network structure with 10 symptoms (three symptoms from the Positive and Negative Syndrome Scale, one depressive symptom, and six symptoms related to schema and rumination) as nodes using a Gaussian graphical model. Global and local network metrics were compared within and between the networks over time.

Global network metrics did not differ between the remitters and non-remitters at baseline or 6 months. However, the network structure and nodal strengths associated with positive-self and positive-others scores changed significantly in the remitters over time. Unique central symptoms for remitters and non-remitters were cognitive brooding and negative-self, respectively. The correlation stability coefficients for nodal strength were within the acceptable range.

Our findings indicate that network structure and some nodal strengths were more flexible in remitters. Negative-self could be an important target for therapeutic intervention.

This study investigates the relationship between insomnia and cognitive dysfunctions including, subjective memory impairment (SMI), mild cognitive impairment (MCI), and dementia, by considering depression in a community sample of elderly individuals.

Data for 1,740 elderly individuals aged 65 years and over were obtained from a nationwide dementia epidemiological study conducted in South Korea. Cognitive functional status was assessed by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet Clinical Assessment Battery. Insomnia was defined as the presence of at least one of the four sleep complaints (difficulty in initiating sleep, difficulty in maintaining sleep, early morning awakening, and non-restorative sleep), accompanied by moderate to severe daytime consequences. Depression was evaluated using the Geriatric Depression Scale.

The prevalence of insomnia in the patients with SMI, MCI, and dementia was found to be 23.2%, 19.6%, and 31.0%, respectively. The patients with SMI, MCI, and dementia were significantly more likely to have insomnia and the four sleep complaints than the normal comparison patients. After adjusting for sociodemographic factors, the significant relationships between cognitive dysfunctional status and insomnia remained. However, after adjusting for sociodemographic factors and depression, no significant relationships with any of the sleep complaints or insomnia remained.

Insomnia is a very common complaint in the elderly with SMI, MCI, and dementia. Depression might play an important factor in the relationship between insomnia and cognitive dysfunctional status in the elderly.

Postural instability is one of the most disabling features of Parkinson's disease, usually occurring in late and advanced stages. The aim of this study was to investigate the postural performance of early-stage de novo Parkinson's disease patients with no clinical postural instability using computerized dynamic posturography. We sought to understand the relationship between postural sway and disease severity and the relationship between postural instability quantitatively measured by computerized dynamic posturography and cognitive impairment in early-stage Parkinson's disease patients.

Thirty-one subjects with Parkinson's disease and 20 healthy controls were assessed by the computerized dynamic posturography protocol using the sensory organization test and the motor control test. A neuropsychological assessment was also administered.

The mean equilibrium score for sensory organization test and the vestibular input ratio were significantly correlated with Hoehn-Yahr stage. No associations between motor latency for any motor control test condition and Hoehn-Yahr stage were found. The equilibrium score for sensory organization test correlated with the mini-mental status examination scores. There was a significant correlation between motor latency for large backward translation and mini-mental status examination scores. There were significant correlations between visual perception/construction/ memory of the neuropsychological battery test and the equilibrium score for sensory organization test and between verbal word learning test, controlled word association test and motor latency for large backward translation.

These findings showed the postural instability present in early-stage (Hoehn-Yahr stage 2-2.5) Parkinson's disease. We also found a close relationship between postural instability and cognitive function in Parkinson's disease patients.

We examined the effects of various exercise intensities on recovery from middle cerebral artery occlusion (MCAO) in rats.

First, we administered a 120-minute left MCAO to male Sprague-Dawley rats and randomly assigned them to one of four groups: no exercise (Group 1), mild exercise (Group 2), moderate exercise (Group 3), and severe exercise (Group 4). Then, we trained the rats for 30 min per day for one week or two weeks. We used a five-point neurological evaluation scale to measure neurological deficits 1-day, 4-days, 7-days, 10-days and 14-days after MCAO and measured infarct volume by use of 2% 2,3,4-triphenyltetrazolium chloride in exercised brains. We also performed immunohistochemistry analysis of the brain to observe reactive astrocytosis at the peri-infarct region.

Neurological examination indicated that Group 2 and 3 recovered better than Group 1 after one week and two weeks (p<0.05). Moreover, Group 2 and 3 had reduced brain infarct volume compared with Group 1 after one week (p<0.05). There were no significant differences between Group 4 and Group 1. The thickness of the peri-infarct astrocytosis was significantly reduced in Group 4 relative to Group 1 after one week. There was a significant negative correlation between the extent of reactive astrocytosis and neurological recovery (r= -0.648, p<0.01).

This study demonstrates that mild to moderate exercise that begins soon after induced cerebral ischemia promotes recovery and that astrocytes may have an important role in the recovery process.

Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time.

The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity.

Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity.

The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.

Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD).

We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years).

As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD.

Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.