Evaluation of a Nondepleted Plasma Multiprotein-Based Model for Discriminating Psychiatric Disorders Using Multiple Reaction Monitoring-Mass Spectrometry: Proof-of-Concept Study.

Psychiatric evaluation relies on subjective symptoms and behavioral observation, which sometimes leads to misdiagnosis. Despite previous efforts to utilize plasma proteins as objective markers, the depletion method is time-consuming. Therefore, this study aimed to enhance previous quantification methods and construct objective discriminative models for major psychiatric disorders using nondepleted plasma. Multiple reaction monitoring-mass spectrometry (MRM-MS) assays for quantifying 453 peptides in nondepleted plasma from 132 individuals [35 major depressive disorder (MDD), 47 bipolar disorder (BD), 23 schizophrenia (SCZ) patients, and 27 healthy controls (HC)] were developed. Pairwise discriminative models for MDD, BD, and SCZ, and a discriminative model between patients and HC were constructed by machine learning approaches. In addition, the proteins from nondepleted plasma-based discriminative models were compared with previously developed depleted plasma-based discriminative models. Discriminative models for MDD versus BD, BD versus SCZ, MDD versus SCZ, and patients versus HC were constructed with 11 to 13 proteins and showed reasonable performances (AUROC = 0.890-0.955). Most of the shared proteins between nondepleted and depleted plasma models had consistent directions of expression levels and were associated with neural signaling, inflammatory, and lipid metabolism pathways. These results suggest that multiprotein markers from nondepleted plasma have a potential role in psychiatric evaluation.

Longitudinal symptom network structure in first-episode psychosis: a possible marker for remission.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clozapine Blood Concentration Predicts Corrected QT-Interval Prolongation in Patients With Psychoses.

BACKGROUND: Corrected QT-interval (QTc) prolongation (QTP) is a rare but fatal adverse effect of antipsychotics. Clozapine is the only antipsychotic recommended for treatment of resistant schizophrenia; however, clozapine has been reported to cause QTP. We sought factors predictive of QTP in patients who had antipsychotic polypharmacy involving clozapine. We explored whether the clozapine blood concentration might predict QTP. METHODS: We included 133 patients with schizophrenia spectrum disorder who had antipsychotic polypharmacy involving clozapine. We used the χ2 and nonparametric tests to compare clozapine therapeutic drug monitoring (TDM) values and QTc-prolonged person (QTPP) status. Multivariate regression and mediator models were used to identify risk factors for QTPP status and QTP. RESULTS: In total, 111 patients were prescribed clozapine. The QTPP rates were 31.3% (20) for men and 23.2% (16) for women. Compared with the non-QTPP group, the QTPP group exhibited significantly higher daily dose of all antipsychotics including clozapine, a higher clozapine dose, and elevated clozapine and norclozapine TDM values. Furthermore, such patients were prescribed a greater number of antipsychotics. Multivariate logistic regression revealed that only the clozapine TDM value could be predictive factor for QTPP status (P = 0.018). A clozapine TDM value above the therapeutic range (>600 mg/dL) was associated with a high risk of QTPP status (adjusted odds ratio, 6.5; 95% confidence interval, 1.7-25.2; P = 0.006). The mediator model revealed that the clozapine TDM values completely mediated the association between the clozapine dose and the QTc interval. CONCLUSIONS: The clozapine blood concentration reliably predicts QTP in patients with clozapine use.

Quantitative Proteomic Approach for Discriminating Major Depressive Disorder and Bipolar Disorder by Multiple Reaction Monitoring-Mass Spectrometry.

Because major depressive disorder (MDD) and bipolar disorder (BD) manifest with similar symptoms, misdiagnosis is a persistent issue, necessitating their differentiation through objective methods. This study was aimed to differentiate between these disorders using a targeted proteomic approach. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was performed to quantify protein targets regarding the two disorders in plasma samples of 270 individuals (90 MDD, 90 BD, and 90 healthy controls (HCs)). In the training set (72 MDD and 72 BD), a generalizable model comprising nine proteins was developed. The model was evaluated in the test set (18 MDD and 18 BD). The model demonstrated a good performance (area under the curve (AUC) >0.8) in discriminating MDD from BD in the training (AUC = 0.84) and test sets (AUC = 0.81) and in distinguishing MDD from BD without current hypomanic/manic/mixed symptoms (90 MDD and 75 BD) (AUC = 0.83). Subsequently, the model demonstrated excellent performance for drug-free MDD versus BD (11 MDD and 10 BD) (AUC = 0.96) and good performance for MDD versus HC (AUC = 0.87) and BD versus HC (AUC = 0.86). Furthermore, the nine proteins were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions. This proof-of-concept study introduces a potential model for distinguishing between the two disorders.

A Prospective Study for Prediction of Psychotic Relapse Using the Korean Early Signs Scale in Patients With Schizophrenia.

INTRODUCTION: A psychotic relapse of schizophrenia is commonly preceded by nonpsychotic behavioral symptoms and signs, and detection of these early signs may enable prevention of relapse of schizophrenia. This study aimed to test the predictive validity of a Korean version of Early Signs Scale (K-ESS) for psychotic relapse for detecting the early signs. MATERIALS AND METHODS: In this multicenter noninterventional 52-week prospective study, outpatients diagnosed as having schizophrenia within 5 years were recruited. The K-ESS and Clinical Global Impression-Severity (CGI-S) scale were administered monthly until the end of the study or the relapse. The primary objective was to determine an optimal cutoff point of K-ESS score for prediction of psychotic relapse. The secondary objective was to assess the concurrent validity of the K-ESS using CGI-S scale. RESULTS: Among the 162 included patients, 14 (8.6%) relapsed during the 52-week study period. The optimal cutoff score of K-ESS was 15 with a sensitivity of 71.43% and a specificity of 52.70%, indicating poor predictive accuracy of K-ESS. A lower cutoff K-ESS score of 3 and a higher cutoff score of 28 were found in the subgroups with milder (CGI-S = 1-2) and severer (CGI-S = 3-4) symptom severity, respectively, with fair to good predictive accuracy. The K-ESS showed acceptable concurrent validity with CGI-S and concordance rate between self-rated and informant-rated scores. DISCUSSION: The predictive accuracy of K-ESS was limited by evaluation interval of a month. At least fortnightly follow-up would be needed for detection of early signs to prevent a psychotic relapse in schizophrenia.

Genetic association study of CSNK1E gene in bipolar disorder and circadian characteristics.

BACKGROUND: A circadian rhythm disturbance is one of the essential components of the phenotype of bipolar disorder. It has been reported that casein kinase 1 epsilon (CSNK1E), a member of the clock gene family, is associated with psychiatric phenotypes. OBJECTIVES: We performed a genetic association study to determine the genetic role of CSNK1E in bipolar disorder and circadian rhythm disturbances in the Korean population. METHODS: The present study included 215 patients with bipolar disorder and 773 controls. Circadian characteristics were measured by the Korean version of the Composite Scale of Morningness (CS). Single-nucleotide polymorphisms (SNPs) of CSNK1E, rs1534891 and rs2075984, were genotyped. Chi-square analyses were performed to evaluate associations involving alleles and genotypes. Haplotype analysis was also performed, and the permutation p value was calculated. We also tested further associations involving these SNPs and scores on the CS. RESULTS: We found a positive association between SNP rs2075984 and bipolar disorder in both the allelic (p = .003) and genotypic (p = .006) distributions. No allelic or genotypic association between SNP rs1534891 and bipolar disorder was observed. A significant association of haplotype with bipolar disorder was found (p = .033). However, no association between the CS and the genotype of either SNP was found in the total sample. CONCLUSION: CSNK1E SNP rs2075984 seemed to play a significant role in the development of bipolar disorder in this Korean sample. This association does not seem to relate to the phase preference measured by the CS. Further studies on CSNK1E with larger samples and more SNPs are necessary.

Clinical, cognitive, and functional characteristics of recent-onset psychosis with autistic features: A 2-year longitudinal study.

Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.

Genome-wide association study and polygenic risk score analysis for schizophrenia in a Korean population.

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10-11; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R2 = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Nanoscale mapping of Ag anode surface potential for high-performance T-organic light-emitting diode using kelvin probe force microscopy.

In this paper, the atmospheric pressure oxygen plasma was used to increase the work function of Ag thin films surface. But Ag thin films was generally not considered as an ideal bottom anode for T-OLED due to its rather low work function (approximately 4.2 eV). Using plasma treatment, the work function of Ag films was increased up to 4.84 eV at the plasma treatment time of between 60 and 90 s. The KPFM and Nano-indenter method analyzed and measured the work function of nano-distribution and nano-mechanical properties of Ag films surface. From the KPFM and Nano-indenter analysis, the stresses of Ag thin films were generated by induced oxygen radicals during the plasma treatment, and the work function of Ag thin film on nano-surface also changed by induce stress. It is can be explained that the nanosurface of thin-film would be generated the stress during the plasma treatment and the induced stress could change the surface property due to increase its volume. It is plausible that the induced stress was accelerated the production of AgO or AgO2 and excessive volume expansion of AgO2 could damage the surface.

Safety and effectiveness of vortioxetine for major depressive disorder: Real-world evidence from a population-based study in South Korea.

Background: A post-marketing surveillance study was conducted to assess the real-world safety and effectiveness of vortioxetine for the treatment of major depressive disorder (MDD) in South Korea. Methods: Adult patients aged 19-94 years receiving vortioxetine for MDD at 72 hospitals and clinics in South Korea between 19th August 2014 and 18th August 2020 were included. Patients were followed for up to 24±2 weeks, at up to three visits. Adverse events (AEs) and effectiveness, assessed by both clinician and patient-reported measures, were analyzed. Results: A total of 3,263 patients (mean age: 51.28 years) were included in the safety set; 1,095 were aged ≥65 years. The majority of the safety set (61.97%) were female. The overall rate of any AEs and serious AEs were 17.13 and 1.56%, respectively. The majority of AEs were mild (88.32%). The rates of AEs did not differ statistically by age (≥65 years: 16.89% [185/1,095] versus <65 years: 17.25% [374/2,168)], p=0.7989), sex (male: 15.95% [198/1,241] versus female: 17.85% [361/2,022], p=0.1623), or liver impairment (with liver impairment: 20.90% [14/67] versus without liver impairment: 17.05% [545/3,196], p=0.4087). Effectiveness was assessed in 1,918 patients. By 24±2 weeks, there were significant clinical improvements from baseline, assessed by change in Montgomery-Asberg Depression Rating Scale total score (mean±standard deviation [SD]: -10.49±9.42 points, p <0.0001), the proportion of patients with improved symptoms using the Clinical Global Impression - Improvement scores (79.29%), and in both patient-reported measures, with a significant improvement in the Korean Version of the Perceived Deficits Questionnaire-Depression (mean±SD: -6.06±13.23, p <0.0001) and Digit Symbol Substitution Test (mean±SD: 4.83±9.81, p <0.0001) total scores from baseline. Similar to the safety profiles, the proportions of patients with improved symptoms compared with baseline using the Clinical Global Impression - Improvement scores did not differ by age (≥65 years: 82.09% versus <65 years: 78.32%, p=0.0511), sex (male: 77.45% versus female: 81.01%, p=0.0587), or liver impairment (with liver impairment: 67.57% versus without liver impairment: 79.85%, p=0.0663). Conclusion: Vortioxetine appears to be well-tolerated and effective for treating MDD patients in the real-world setting in South Korea, irrespective of age, sex, and liver impairment, reflecting the known profile of vortioxetine based on studies worldwide.

Latent class analysis of psychotic-affective disorders with data-driven plasma proteomics.

Data-driven approaches to subtype transdiagnostic samples are important for understanding heterogeneity within disorders and overlap between disorders. Thus, this study was conducted to determine whether plasma proteomics-based clustering could subtype patients with transdiagnostic psychotic-affective disorder diagnoses. The study population included 504 patients with schizophrenia, bipolar disorder, and major depressive disorder and 160 healthy controls, aged 19 to 65 years. Multiple reaction monitoring was performed using plasma samples from each individual. Pathologic peptides were determined by linear regression between patients and healthy controls. Latent class analysis was conducted in patients after peptide values were stratified by sex and divided into tertile values. Significant demographic and clinical characteristics were determined for the latent clusters. The latent class analysis was repeated when healthy controls were included. Twelve peptides were significantly different between the patients and healthy controls after controlling for significant covariates. Latent class analysis based on these peptides after stratification by sex revealed two distinct classes of patients. The negative symptom factor of the Brief Psychiatric Rating Scale was significantly different between the classes (t = -2.070, p = 0.039). When healthy controls were included, two latent classes were identified, and the negative symptom factor of the Brief Psychiatric Rating Scale was still significant (t = -2.372, p = 0.018). In conclusion, negative symptoms should be considered a significant biological aspect for understanding the heterogeneity and overlap of psychotic-affective disorders.

Predictors of full recovery in patients with early stage schizophrenia spectrum disorders.

To promote recovery in psychosis, targeting modifiable factors related to recovery is critical. Using more strict definition of full recovery, we examined predictors for recovery in patients with early stage schizophrenia spectrum disorders (SSD) followed up to 6.5 years. The target subjects were 375 patients with early stage SSD who had been over at least 1-year after registration and evaluated. The criteria for full recovery were having the score of the Positive and Negative Syndrome Scale (PANSS) 8-item ≤ 2 and adequate functional recovery for at least 1-year. We performed univariate Cox and stepwise Cox regression in both total and acute patients. In stepwise Cox regression, several independent predictors for recovery, i.e., negative symptoms of the PANSS, duration of untreated psychosis (DUP) and non-professional job were identified in patients with early stage SSD. In acute patients, other factors such as professional job and subjective well-being under neuroleptics were more important. The present study identified independent predictors for recovery modifiable by various psychosocial intervention and early intervention services. Moreover, it highlights the need of providing different treatment strategies depending on clinical status.

Network analysis of plasma proteomes in affective disorders.

The conventional differentiation of affective disorders into major depressive disorder (MDD) and bipolar disorder (BD) has insufficient biological evidence. Utilizing multiple proteins quantified in plasma may provide critical insight into these limitations. In this study, the plasma proteomes of 299 patients with MDD or BD (aged 19-65 years old) were quantified using multiple reaction monitoring. Based on 420 protein expression levels, a weighted correlation network analysis was performed. Significant clinical traits with protein modules were determined using correlation analysis. Top hub proteins were determined using intermodular connectivity, and significant functional pathways were identified. Weighted correlation network analysis revealed six protein modules. The eigenprotein of a protein module with 68 proteins, including complement components as hub proteins, was associated with the total Childhood Trauma Questionnaire score (r = -0.15, p = 0.009). Another eigenprotein of a protein module of 100 proteins, including apolipoproteins as hub proteins, was associated with the overeating item of the Symptom Checklist-90-Revised (r = 0.16, p = 0.006). Functional analysis revealed immune responses and lipid metabolism as significant pathways for each module, respectively. No significant protein module was associated with the differentiation between MDD and BD. In conclusion, childhood trauma and overeating symptoms were significantly associated with plasma protein networks and should be considered important endophenotypes in affective disorders.

Childhood attention deficit hyperactivity disorder features in adult mood disorders.

A significant overlap between childhood mood disorders and many aspects of attention deficit hyperactivity disorder (ADHD) has been established. High rates of co-occurrence, familial aggregation, and more severe clinical manifestations of the illnesses when they are comorbid suggest that common genetic and environmental factors may contribute to the development of both disorders. Research on the co-occurrence of childhood ADHD and mood disorders in childhood has been conducted. We retrospectively investigated childhood ADHD features in adults with mood disorders. Childhood ADHD features were measured with the Korean version of the Wender Utah Rating Scale (WURS). The sample consisted of 1305 subjects: 108 subjects were diagnosed with bipolar disorder type I, 41 with bipolar disorder type II, 101 with major depressive disorder, and 1055 served as normal controls. We compared total WURS scores as well as scores on 3 factors (impulsivity, inattention, and mood instability and anxiety) among the 4 different diagnostic groups. The 4 groups differed significantly from one another on all scores. The group with bipolar disorder type II obtained the highest total scores on the WURS. The impulsivity and inattention associated with childhood ADHD were more significantly related to bipolar disorder type II than with bipolar disorder type I. The mood instability and anxiety associated with childhood ADHD seem to be significantly related to major depressive disorder in adulthood. In conclusion, multifactorial childhood ADHD features were associated with mood disorders of adulthood.

The Anti-Tumor Effect of Boron Neutron Capture Therapy in Glioblastoma Subcutaneous Xenograft Model Using the Proton Linear Accelerator-Based BNCT System in Korea.

Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells and is being actively researched and developed around the world. In Korea, development of the proton linear accelerator-based BNCT system has completed development, and its anti-cancer effect in the U-87 MG subcutaneous xenograft model has been evaluated. To evaluate the efficacy of BNCT, we measured 10B-enriched boronophenylalanine (BPA) uptake in U-87 MG, FaDu, and SAS cells and evaluated cell viability by clonogenic assays. In addition, the boron concentration in the tumor, blood, and skin on the U-87 MG xenograft model was measured, and the tumor volume was measured for 4 weeks after BNCT. In vitro, the intracellular boron concentration was highest in the order of SAS, FaDu, and U-87 MG, and cell survival fractions decreased depending on the BPA treatment concentration and neutron irradiation dose. In vivo, the tumor volume was significantly decreased in the BNCT group compared to the control group. This study confirmed the anti-cancer effect of BNCT in the U-87 MG subcutaneous xenograft model. It is expected that the proton linear accelerator-based BNCT system developed in Korea will be a new option for radiation therapy for cancer treatment.

The factor structure and clinical utility of clinician-rated dimensions of psychosis symptom severity in patients with recent-onset psychosis: Results of a 1-year longitudinal follow-up prospective cohort study.

The classic subtype classification of schizophrenia has been removed, and DSM-5 now includes the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS). In the present study, a factor analysis of the CRDPSS was performed, and we assessed whether patient classification using the derived factor structure helps predict the clinical course. The participants were 390 patients with recent-onset psychosis enrolled in the Korean Early Psychosis Cohort Study (KEPS). Two factors were identified: psychotic (including delusions, hallucinations, disorganization, and abnormal psychomotor behavior) and negative-cognitive (including negative symptoms and impaired cognition). Patients were grouped based on the factor structure and changes in clinical course were monitored over 1 year. The negative-cognitive group demonstrated longer duration of untreated psychosis, earlier onset, and a higher rate of psychiatric comorbidities. Baseline Positive and Negative Syndrome Scale (PANSS) total and Clinical Global Impression-Severity (CGI-S) scores were higher in psychotic group, but group differences were not observed after 2 months. Conversely, the PANSS negative scale score was significantly higher in negative-cognitive group throughout follow-up, and CGI-S score was reversed at 12 months. The findings indicate that the factor structure derived herein for the CRDPSS could be helpful for predicting the clinical course of recent-onset psychosis patients.

DNA Methylation Profiles of the DRD2 and NR3C1 Genes in Patients with Recent-Onset Psychosis.

Objectives: Dopamine receptor D2 gene (DRD2) and glucocorticoid receptor gene (NR3C1) are implicated in the development of psychosis. We investigated methylation levels of DRD2 and NR3C1 in peripheral blood of patients with recent-onset (RO) psychosis using bisulfite pyrosequencing as well as its association with childhood trauma and rumination. Methods: In all, 51 individuals with RO psychosis and 47 healthy controls were recruited. DNA methylation levels in the targeted regions of two genes were analyzed and compared. Childhood trauma and rumination were evaluated using the Early Trauma Inventory Self-Report Short Form (ETI-SF) and Brooding Scale (BS), respectively. Correlations between the scores of the ETI-SF and BS and methylation levels were explored. Results: For DRD2, we found no significant differences between groups in terms of methylation level or association with childhood trauma or rumination. For NR3C1, we found a trend level significance for average value of all CpG sites and significant hypermethylation or hypomethylation at specific sites. There was also a significant positive correlation between the methylation level at the CpG8 site of NR3C1 exon 1F and negative symptom subscale score of the PANSS (PANSS-N). Conclusion: Epigenetic alterations of NR3C1 are associated with the pathophysiology of psychosis. Further epigenetic studies will elucidate the molecular mechanisms underpinning the pathophysiology of psychosis.

Three-year outcomes and predictors for full recovery in patients with early-stage psychosis.

In the present study, various outcomes over 3-year period in patients with early stage psychosis including remission, recovery, relapse and medication adherence were investigated. Predictor for full recovery at year 3 was also examined. Three-year follow-up data in 534 patients with schizophrenia spectrum disorders (SSD) and psychotic disorder not otherwise specified (PNOS) were examined for overall outcome trajectories. The data of completers at year 3 (n = 157) were used to identify predictors for recovery using logistic regression. The rates of symptomatic remission and full recovery at 6-, 12-, 24-, and 36-month follow-up were 76.10, 69.20, 79.50, and 79.10%, and 22.80, 26.40, 28.60, and 39.60%, respectively. The rates of drop-out and relapse at 6-, 12-, 24-, and 36-month follow-up were 25.4, 29.5, 38.6, and 51.1%, and 3.7, 8.9, 19.0, and 38.9%, respectively. The rates of good adherence and prescription of Long-Acting Injectable Antipsychotics (LAIA) at 6-, 12-, 24- and 36-month follow-up were 87.8, 88.0, 91.9, and 93.9%, and 18.3, 21.7, 22.0, and 25.5%, respectively. Significant predictors for full recovery were duration of untreated psychosis (DUP), family intimacy and physical activity. We observed similar or better results on remission, recovery, and relapse rates compared to other previous studies. Effective psychosocial intervention should be provided to shorten the gap between remission and recovery rates and to address DUP, family issues, and exercise to enhance recovery.

Symptomatic and full remission rates in first-episode psychosis: A 12-month follow-up study in Korea.

AIM: In the present study, the prevalence and predictors of symptomatic and full remission were investigated in patients with first-episode psychosis (FEP) at the 12-month follow-up. METHODS: A total of 308 participants aged 18-45 years fulfilled the study inclusion criteria and 214 completed the 12-month follow-up. RESULTS: At the 12-month follow-up, 67.3% (142) and 25.9% (55) of the FEP patients met the criteria for symptomatic and full remission, respectively. Stepwise logistic regression analysis showed a shorter duration of untreated psychosis (DUP), no family history, lower Positive and Negative Syndrome Scale (PANSS) negative symptom scores at baseline and higher familial support predicted symptomatic remission at the 12-month follow-up. A higher educational level, shorter DUP, lower PANSS general symptoms scores at baseline and higher subjective well-being under neuroleptics emotional regulation scores predicted full remission. CONCLUSIONS: Our findings regarding the rates of symptomatic and full remission are consistent with previous studies. The results indicate a large discrepancy between symptomatic versus full remission rates at a 12-month follow-up in patients with FEP. Effective psychosocial interventions are necessary to improve the outcomes of FEP patients.