White matter tract alterations in schizophrenia identified by DTI-based probabilistic tractography: a multisite harmonisation study.

INTRODUCTION: It has been suggested that schizophrenia involves dysconnectivity between functional brain regions and also the white matter structural disorganisation. Thus, diffusion tensor imaging (DTI) has widely been used for studying schizophrenia. However, most previous studies have used the region of interest (ROI) based approach. We, therefore, performed the probabilistic tractography method in this study to reveal the alterations of white matter tracts in the schizophrenia brain. METHODS: A total of four different datasets consisted of 189 patients with schizophrenia and 213 healthy controls were investigated. We performed retrospective harmonisation of raw diffusion MRI data by dMRIharmonisation and used the FMRIB Software Library (FSL) for probabilistic tractography. The connectivities between different ROIs were then compared between patients and controls. Furthermore, we evaluated the relationship between the connection probabilities and the symptoms and cognitive measures in patients with schizophrenia. RESULTS: After applying Bonferroni correction for multiple comparisons, 11 different tracts showed significant differences between patients with schizophrenia and healthy controls. Many of these tracts were associated with the basal ganglia or cortico-striatal structures, which aligns with the current literature highlighting striatal dysfunction. Moreover, we found that these tracts demonstrated statistically significant relationships with few cognitive measures related to language, executive function, or processing speed. CONCLUSION: We performed probabilistic tractography using a large, harmonised dataset of diffusion MRI data, which enhanced the statistical power of our study. It is important to note that most of the tracts identified in this study, particularly callosal and cortico-striatal streamlines, have been previously implicated in schizophrenia within the current literature. Further research with harmonised data focusing specifically on these brain regions could be recommended.

Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation Versus Microfracture for the Treatment of Articular Cartilage Defects: A 5-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Costal chondrocyte-derived pellet-type autologous chondrocyte implantation (CCP-ACI) has been introduced as a new therapeutic option for the treatment of articular cartilage defects. We had previously conducted a randomized controlled trial comparing CCP-ACI versus microfracture at 1 year postoperatively. PURPOSE: To compare the efficacy and safety of CCP-ACI versus microfracture for the treatment of articular cartilage defects of the knee at 5 years postoperatively. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: This study describes the mean 5-year follow-up of a previously published prospective clinical trial. The previous prospective trial compared the results of CCP-ACI versus microfracture until 1 year of follow-up. Of the 30 patients who were included in the previous study, 25 were followed up for 5 years. Patients were evaluated based on clinical outcome scores (Lysholm score, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score [KOOS], and visual analog scale for pain), magnetic resonance imaging findings, and rates of treatment failure at last follow-up. RESULTS: The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in the CCP-ACI group was significantly higher than that in the microfracture group at 5 years (62.3 vs 26.7, respectively; P < .0001). The Lysholm score and KOOS score in the CCP-ACI group were significantly higher than those in the microfracture group at 5 years (84.5 vs 64.9, respectively, and 390.9 vs 303.0, respectively; P = .023 and P = .017, respectively). There was 1 case of treatment failure that occurred in the microfracture group. CONCLUSION: The present randomized controlled trial indicated that the results of both procedures clinically and statistically significantly improved at 1 and 5 years' follow-up in treating cartilage defects, but the results of CCP-ACI were superior to those of microfracture. Magnetic resonance imaging conducted at 1 year and 5 years after CCP-ACI revealed statistically significant superior structural integration with native cartilage tissue compared with microfracture. REGISTRATION: NCT03545269 (ClinicalTrials.gov).

Structural variability of the cerebral cortex in schizophrenia and its association with clinical symptoms.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Structural impairment in superficial and deep white matter in schizophrenia.

OBJECTIVE: Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects. METHODS: We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing. RESULTS: Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing. CONCLUSION: We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.

Linguistic anomalies observed in the Sentence Completion Test in patients with schizophrenia.

BACKGROUND: Schizophrenia is a chronic, debilitating disorder characterised by distorted thinking, perceptions, behaviours, and even language impairments. We investigated the linguistic anomalies in Korean schizophrenia patients compared to non-psychotic psychiatric controls to determine whether the linguistic anomalies in English speakers with schizophrenia were replicated in Korean speakers. METHODS: Thirty-four schizophrenia patients and 70 non-psychotic psychiatric controls were included in this study. The SCT was utilised as the text data for analysis. For linguistic analysis, we evaluated texts regarding semantics and syntax. We separately counted the number of semantic or syntactic errors in the written texts of study participants and compared them between patients and controls. RESULTS: Schizophrenia patients showed significantly more semantic errors (p < .001) and syntactic errors (p < .001) per 1,000 characters than non-psychotic psychiatric controls. Specifically, inappropriate word or syntactic component selection is noticeable in schizophrenia patients. These differences were still significant after adjusting for general intelligence measured by the K-WAIS-IV. CONCLUSION: Schizophrenia patients showed both semantic and syntactic errors in written language. Moreover, these errors seemed to be partly independent of general intelligence. Notably, patients showed a noticeable number of syntactic errors. Further investigation into the language of patients with schizophrenia and schizophrenia-spectrum disorders is required.

Prolonged Unmet Mental Health Needs of the 2017 Pohang Earthquake Survivors.

OBJECTIVE: Two years after the 2017 Pohang earthquake, some people sought follow-up mental health support. The demographic and clinical characteristics of this unique group of people were investigated to identify some insights on the predisposing factors of the longterm need for psychiatric help after a severe earthquake disaster. METHODS: De-identified data from those seeking mental health support 2 years after the 2017 Pohang earthquake were used. The descriptive statistics of demographic and clinical characteristics of the study group was identified and paired with general population data obtained from open and public governmental websites. Sex, age distribution, destruction of house, and psychiatric disorder were compared between the follow-up sample and general population. RESULTS: The proportion of women in the group seeking support was two times higher than that in the general population, and people ages between 50 and 70 years commonly sought support. The severity of home destruction was higher among people who sought and needed follow-up mental health support programs than in the general population. There was a higher proportion of people with psychiatric disorders in the group seeking support than in the general population. CONCLUSION: The need for long-term mental health support 2 years after an earthquake was higher in women than in men and those aged between 50 and 70 years, and those with a previous psychiatric history and with a higher severity of home destruction, which lead to necessitating leaving the home. Future earthquake response should include screening and psychiatric treatment referral and residential support in vulnerable people.

Characterization of the extracellular free water signal in schizophrenia using multi-site diffusion MRI harmonization.

Studies applying Free Water Imaging have consistently reported significant global increases in extracellular free water (FW) in populations of individuals with early psychosis. However, these published studies focused on homogenous clinical participant groups (e.g., only first episode or chronic), thereby limiting our understanding of the time course of free water elevations across illness stages. Moreover, the relationship between FW and duration of illness has yet to be directly tested. Leveraging our multi-site diffusion magnetic resonance imaging(dMRI) harmonization approach, we analyzed dMRI scans collected by 12 international sites from 441 healthy controls and 434 individuals diagnosed with schizophrenia-spectrum disorders at different illness stages and ages (15-58 years). We characterized the pattern of age-related FW changes by assessing whole brain white matter in individuals with schizophrenia and healthy controls. In individuals with schizophrenia, average whole brain FW was higher than in controls across all ages, with the greatest FW values observed from 15 to 23 years (effect size range = [0.70-0.87]). Following this peak, FW exhibited a monotonic decrease until reaching a minima at the age of 39 years. After 39 years, an attenuated monotonic increase in FW was observed, but with markedly smaller effect sizes when compared to younger patients (effect size range = [0.32-0.43]). Importantly, FW was found to be negatively associated with duration of illness in schizophrenia (p = 0.006), independent of the effects of other clinical and demographic data. In summary, our study finds in a large, age-diverse sample that participants with schizophrenia with a shorter duration of illness showed higher FW values compared to participants with more prolonged illness. Our findings provide further evidence that elevations in the FW are present in individuals with schizophrenia, with the greatest differences in the FW being observed in those at the early stages of the disorder, which might suggest acute extracellular processes.

Antipsychotic treatment and risk of discontinuation and hospitalization in first-episode schizophrenia: a nationwide population-based study.

BACKGROUND: Current evidence on antipsychotic treatment and risk of psychiatric hospitalization in first-episode schizophrenia (FES) is largely based on the findings from randomized clinical trials (RCTs). However, the generalization of the findings to real-world patients is limited due to inherent caveats of the RCT. We aimed to investigate the treatment discontinuation and risk of psychiatric hospitalization using a nationwide population database. METHODS: The Health Insurance Review Agency database in South Korea was obtained, and the observation period started from 1 January 2009 to 31 December 2016. We defined the maintenance period as the period from 6-month after the diagnosis of schizophrenia, which is utilized for the main results. For a total of 44 396 patients with FES, a within-individual Cox regression model was used to compare the risk of the treatment discontinuation and psychiatric hospitalization. RESULTS: In group comparison, a long-acting injectable (LAI) antipsychotic group was associated with the lowest risk of the treatment discontinuation (0.64, 0.55-0.75) and psychiatric hospitalization (0.29, 0.22-0.38) in comparison with a typical antipsychotic group and no use, respectively. Among individual antipsychotics, the lowest risk of the treatment discontinuation was observed in LAI paliperidone (0.46, 0.37-0.66) compared to olanzapine. Clozapine was found to be the most effective antipsychotic in lowering the risk of psychiatric hospitalization as monotherapy compared to no use (0.23, 0.18-0.31). CONCLUSIONS: In real-world patients with FES, LAI paliperidone and clozapine were associated with low treatment discontinuation and better effectiveness in lowering the risk of psychiatric hospitalization.

Linguistic anomalies in the language of patients with schizophrenia.

In terms of thought disorder, the language of patients with schizophrenia itself could be a valuable resource. Some valuable studies on the language of patients with schizophrenia have been performed. However, most such studies have been confined to English-speaking countries, or at least those where Indo-European languages are spoken. Therefore, we investigated linguistic anomalies in the language of Korean patients with schizophrenia. Short texts written by 69 patients with schizophrenia from a single mental hospital and matched normal control participants were analyzed. We evaluated these texts in terms of semantic and syntactic errors. Then, we compared the error rates adjusted for text length between patients and normal control participants. We also divided the patients with schizophrenia into two groups by their duration of illness and compared these two groups to investigate the relationship between the duration of illness and linguistic anomalies. The patients with schizophrenia committed a total of 1.86 (2.52) semantic errors and 1.37 (1.79) syntactic errors per 100 characters, which were significantly more frequent than errors committed by normal control participants. Furthermore, there was a notably high number of semantic errors relative to syntactic errors in the language of patients with schizophrenia. Our study results are consistent with previous studies from English-speaking countries, implying that the linguistic anomalies of patients with schizophrenia are not confined to a single language. Because language is essential in mental function, further research on linguistic anomalies in patients with schizophrenia is recommended.

Impact of the early phase of the COVID-19 pandemic on the use of mental health services in South Korea: a nationwide, health insurance data-based study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the utilization of mental health services. Existing evidence investigating this issue at the nationwide level is lacking, and it is uncertain whether the effects of the COVID-19 pandemic on the use of psychiatric services differs based on psychiatric diagnosis. METHODS: Data from the claims database between October 2015 and August 2020 was obtained from the Health Insurance Review and Assessment agency in South Korea. Based on the main diagnostic codes, psychiatric patients were identified and categorized into diagnostic groups (anxiety disorders, bipolar and related disorders, depressive disorders, and schizophrenia spectrum disorders). We calculated the number of psychiatric inpatients and outpatients and the medication adherence of patients for each month. We compared the actual and predicted values of outcomes during the COVID-19 pandemic and performed interrupted time-series analyses to test the statistical significance of the impact of the pandemic. RESULTS: During the COVID-19 pandemic, the number of inpatients and admissions to psychiatric hospitals decreased for bipolar and related disorders and depressive disorders. In addition, the number of patients admitted to psychiatric hospitals for schizophrenia spectrum disorders decreased. The number of psychiatric outpatients showed no significant change in all diagnostic groups. Increased medication adherence was observed for depressive, schizophrenia spectrum, and bipolar and related disorders. CONCLUSIONS: In the early phase of the COVID-19 pandemic, there was a trend of a decreasing number of psychiatric inpatients and increasing medication adherence; however, the number of psychiatric outpatients remained unaltered.

Risk of Breast Cancer in Association with the Use of Second-generation Antipsychotics.

Objective: Previous studies regarding the relationship between the risk of breast cancer (BC) and antipsychotics use have reported inconsistent findings. Insufficient sample size and/or observation period may have hindered revealing the risk of BC associated with antipsychotics use. We aimed to investigate whether the use of second-generation antipsychotics (SGA) is associated with increased risk of BC. Methods: We used the Health Insurance Review Agency database in South Korea between 2008 and 2018. The index date was determined as the date of the first antipsychotic prescription. We selected women prescribed SGAs for more than 30 days within a year from the index date and age-matched controls, yielding 498,970 cases and 997,940 controls. The Cox proportional hazards regression model was used for estimating the risk. Results: The incidence rates of BC were 109.74 and 101.51 per 100,000 person-years in the case and control groups, respectively. There was an increased risk of BC in the case group (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.13). There was a higher risk of BC in subjects prescribed with ≥ 10,000 mg of olanzapine equivalent dose (HR = 1.29, 95% CI 1.14-1.46) than those with < 10,000 mg (HR = 1.05, 95% CI 1.00-1.11). The increased risk of BC in the case group became significant after six years of the observation period (≥ 6 years: HR = 1.24, 95% CI 1.14-1.35, 3 to < 6 years: HR = 1.06, 95% CI 0.97-1.15, < 3 years: HR = 1.02, 95% CI 0.95-1.09). Conclusion: This study indicated that the use of SGAs is associated with increased risk of BC in a long-term relationship with a dose-response pattern.

Delay in psychiatric hospitalization from the diagnosis of first-episode schizophrenia and its association with clinical outcomes and direct medical costs: a nationwide, health insurance data-based study.

BACKGROUND: Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. METHODS: The South Korean Health Insurance Review Agency database (2012-2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. RESULTS: Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.005; inpatient care: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.017). CONCLUSIONS: Earlier psychiatric admission from the diagnosis is associated with a decrease in the number of psychiatric admissions as well as in direct medical costs in patients with FES.

Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia: a multisite harmonization study.

Cognitive deficits are among the best predictors of real-world functioning in schizophrenia. However, our understanding of how cognitive deficits relate to neuropathology and clinical presentation over the disease lifespan is limited. Here, we combine multi-site, harmonized cognitive, imaging, demographic, and clinical data from over 900 individuals to characterize a) cognitive deficits across the schizophrenia lifespan and b) the association between cognitive deficits, clinical presentation, and white matter (WM) microstructure. Multimodal harmonization was accomplished using T-scores for cognitive data, previously reported standardization methods for demographic and clinical data, and an established harmonization method for imaging data. We applied t-tests and correlation analysis to describe cognitive deficits in individuals with schizophrenia. We then calculated whole-brain WM fractional anisotropy (FA) and utilized regression-mediation analyses to model the association between diagnosis, FA, and cognitive deficits. We observed pronounced cognitive deficits in individuals with schizophrenia (p < 0.006), associated with more positive symptoms and medication dosage. Regression-mediation analyses showed that WM microstructure mediated the association between schizophrenia and language/processing speed/working memory/non-verbal memory. In addition, processing speed mediated the influence of diagnosis and WM microstructure on the other cognitive domains. Our study highlights the critical role of cognitive deficits in schizophrenia. We further show that WM is crucial when trying to understand the role of cognitive deficits, given that it explains the association between schizophrenia and cognitive deficits (directly and via processing speed).

One-Year Clinical Outcomes Following Electroconvulsive Therapy for Patients with Schizophrenia: A Nationwide Health Insurance Data-Based Study.

Background: Although the use of electroconvulsive therapy (ECT) in the treatment of schizophrenia has decreased since the advent of antipsychotic drugs, ECT is still implemented in several clinical indications. However, a few population-based studies have examined its real-world effectiveness in schizophrenia. Methods: We used data from 2010 to 2019 from the Health Insurance Review and Assessment Service database in the Republic of Korea. We selected 380 schizophrenia patients having more than six ECT sessions and 1140 patient controls matched for age, sex, calendar year at entry, and the number of psychiatric hospitalizations before the time point of start of psychiatric hospitalization for ECT. Antipsychotic treatment discontinuation, psychiatric hospitalization, and direct medical costs were used as measures of clinical outcomes. Multiple regression analysis was used for any group-by-time interaction effect, and 1-year pre- and post-ECT periods were compared within and between the groups. Results: We found a significantly lower number of antipsychotic treatment discontinuations in the ECT group during the 1-year post-ECT period (t=2.195, p=0.028). A larger decrease was found in the number of psychiatric hospitalizations in the ECT group, with a group-by-time interaction effect (p=0.043). The direct medical costs in the 1-year pre- (t=-8.782, p<0.001) and post-ECT periods (t=-9.107, p<0.001) were higher in the ECT group than in the control group, with no significant change across both periods. Conclusion: We found that the ECT group had a larger decrease in the number of psychiatric hospitalizations in the 1-year post-ECT period than the control group.

Surgical treatment of facial blushing: Patient selection and operative technique (retrospective observational study).

Surgeons are often reluctant to offer further intervention to patients with medically intractable facial blushing. This is mainly because of the relatively high failure rate of blushing resolution and a high incidence of compensatory hyperhidrosis. In this study, we sought to identify the type of blushing that would benefit from surgery and minimize compensatory hyperhidrosis by applying diffuse sympathicotomy (DS). This study was a retrospective review of 62 patients who underwent R2 endoscopic thoracic sympathicotomy (ETS) and preemptive DS for facial blushing. Facial blushing was classified as autonomic-mediated blushing (thermoregulatory, emotional) and vasodilator-mediated blushing (constant) based on the history and precipitating factors for blushing. DS was performed at lower-thoracic levels in the form of limited DS (right R5/7/9/11, left R5/6/8/10) or extended DS (bilateral R5-11). Resolution of blushing (described as "almost disappeared") was achieved in 48% of patients with a median follow-up of 19.6 months. There was a significant difference in resolution among 3 types of blushing (emotional: 55%, thermoregulatory: 28%, constant: 15%, P = .03). Multivariate analysis confirmed thermoregulatory and constant type blushing as a potential independent predictor of blushing resolution. Even though there was no difference between the DS procedures with respect to compensatory hyperhidrosis, intolerable compensatory hyperhidrosis (Hyperhidrosis Disease Severity Scale = 4) occurred in only 11% of patients. DS redistributed sweating area, being predominantly on the chest and mid-back (89%), also seen on the abdomen-waist-groin-buttocks-thighs (63%). Overall, 77% of patients experienced satisfactory results. Emotional blushing proved to be an established indication of ETS where good long-term results can be expected. Expansion of surgical indication to thermoregulatory or constant type blushing needs to be validated in future studies. Additionally, compensatory hyperhidrosis, another hurdle for ETS, can be minimized by preemptive DS, resulting in redistribution and decrease of sweating.

Comparative effectiveness of antipsychotic monotherapy and polypharmacy in schizophrenia patients with clozapine treatment: A nationwide, health insurance data-based study.

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia (TRS). However, it remains uncertain whether antipsychotic augmentation to clozapine has the superior effectiveness over clozapine alone and the effect size of clozapine compared to other antipsychotic drugs in TRS. Therefore, we examined the comparative effectiveness of antipsychotic monotherapy and polypharmacy on the risk of psychiatric admission and treatment discontinuation in TRS. Data were collected from the Health Insurance Review Agency database between January 2010 and December 2019 in South Korea. Among prevalent patients with schizophrenia, we defined 22,327 patients with TRS as those who had been prescribed with clozapine at least once during the entire observation period. Stratified Cox proportional hazards regressions were performed using data on all antipsychotic prescriptions of patients with TRS to investigate the risk of psychiatric hospitalization and treatment discontinuation associated with antipsychotic treatment. In individual comparisons, clozapine monotherapy was the most effective for the risk of psychiatric hospitalization compared to no use (hazard ratio [HR] = 0.23, 95% confidence interval [CI] = 0.22-0.25). In group comparisons, clozapine with long-acting injectable (LAI) second-generation antipsychotics (SGA) was superior to clozapine monotherapy for the risk of psychiatric hospitalization (HR = 0.60, 95%CI = 0.41-0.88). Clozapine monotherapy was associated with the lowest risk of treatment discontinuation in the individual and group comparisons. This retrospective observational population-based study reports that clozapine with LAI SGA is more effective in lowering the risk of psychiatric hospitalization in antipsychotic group comparison with the reference of clozapine monotherapy.

Risk of treatment discontinuation and psychiatric hospitalization associated with early dose reduction of antipsychotic treatment in first-episode schizophrenia: A nationwide, health insurance data-based study.

AIM: We investigated the impact of early dose reduction of antipsychotic treatment on the risk of treatment discontinuation and psychiatric hospitalization in patients with first-episode schizophrenia (FES). METHODS: The Health Insurance Review Agency database in South Korea was used to include 16 153 patients with FES. At 6 months from their diagnosis, the patients were categorized by the magnitude of dose reduction (no reduction, 0%-50%, and >50%). With a reference of no reduction, the risk of treatment discontinuation and psychiatric hospitalization associated with dose reduction in the 1-year follow-up period after the first 6 months was examined with a Cox proportional hazard ratio model stratified by the mean daily olanzapine-equivalent dose in the first 3 months (<10, 10 to 20, >20 mg/day). RESULTS: A >50% dose reduction was associated with an increased risk of treatment discontinuation in all subgroups (<10 mg/day: hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.24-1.67 [P <0.01]; 10-20 mg/day: HR =1.60, 95% CI =1.37-1.86 [P <0.01]; and >20 mg/day: HR =1.62, 95% CI =1.37-1.91 [P <0.01]). In the subgroup taking <10 mg/day, an association of 0%-50% dose reduction with an increased risk of treatment discontinuation was observed (HR =1.20, 95% CI =1.09-1.31; P <0.01). A > 50% dose reduction was associated with increased risk of psychiatric hospitalization only in the subgroup taking <10 mg/day (HR =1.48, 95% CI =1.21-1.80; P <0.01). CONCLUSIONS: Our results suggest that an above certain dose of antipsychotic drugs is required to prevent psychiatric hospitalization, and extensive dose reduction of antipsychotic drugs could result in a higher risk of treatment discontinuation.

Diagnostic conversion from unipolar to bipolar affective disorder-A population-based study.

OBJECTIVES: It is essential to clinically distinguish bipolar affective disorder from unipolar affective disorders. However, patients previously diagnosed with unipolar affective disorder are sometimes later diagnosed with bipolar affective disorder, known as diagnostic conversion. Here we investigated diagnostic conversion using data from a nationwide population-based register. METHODS: We obtained claims data from 2007 to 2020 in Korea's Health Insurance Review Agency database and identified a cohort of patients who were diagnosed with unipolar depression in 2009 without prior psychiatric diseases within the previous 2 years. We studied the rate of diagnostic conversion and risk factors, especially antidepressants. RESULTS: About 6.5% of patients underwent diagnostic conversion during the observation period. Younger age at disease onset and usage of antidepressants increased the relative risk for diagnostic conversion. Patients using serotonin-norepinephrine reuptake inhibitors (SNRI) showed more than twice the risk compared to no usage of antidepressant. LIMITATION: First, this study was based on the population-based register data. Thus, we defined the patient cohort diagnosed with unipolar depression with strict inclusion criteria. Second, the exposure time differed between different antidepressants. Third, we estimated the relative risk for diagnostic conversion compared to no use of antidepressants. Moreover, we could not rule out the potential influence of antidepressant polypharmacy. CONCLUSION: We confirmed diagnostic conversion in some patients and identified younger age or usage of antidepressants, especially SNRI, as risk factors. Because unipolar and bipolar affective disorders show different disease courses or prognoses and have different treatment strategies, clinicians should be mindful of diagnostic conversion.

Fever as a Side Effect after Electroconvulsive Therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most important and safe nonpharmacological treatment for psychiatric disorders. Some patients experience unexplained fever after ECT, but only a few studies have reported on this. METHOD: We investigated fever after ECT by retrospectively reviewing the medical records of patients. Patients treated at the ECT unit of the Department of Psychiatry at Asan Medical Center, Seoul, South Korea, between 30 June 2004 and 30 June 2019, were included. Differences in variables were compared between groups with or without fever after ECT sessions. RESULT: There were 28 patients (8.8%) in the fever group. Forty-three ECT sessions (1.5%) resulted in fever after treatment. The female-to-male ratio was higher in the fever group than in the control group, and the mean number of total ECT sessions was also higher in the fever group than in the control group, but there were no other differences between the 2 groups. CONCLUSION: Comparing fever and control sessions, fever sessions relatively preceded control sessions and had a longer seizure duration. Postictal delirium occurred more often in the fever sessions than in control sessions. Fever sessions had a higher white blood cell count and lower concomitant quetiapine dosage than control sessions. Because 8.8% of patients who received ECT experienced fever after treatment more than once, fever after ECT is considered to be a common side effect.

Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model.

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.