Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Patient's Perspective on Psychiatric Drugs: A Multicenter Survey-Based Study.

OBJECTIVE: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders. METHODS: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared. RESULTS: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups. CONCLUSION: This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient's preference for the drug may contribute to the improvement of drug compliance and outcomes.

Factors Affecting Fear of COVID-19 Infection in Healthcare Workers in COVID-19 Dedicated Teams: Focus on Professional Quality of Life.

This study examined factors related to high fear of coronavirus disease 2019 (COVID-19) infection in healthcare workers (HCWs) in COVID-19 dedicated teams. We assigned 371 HCWs to low, medium, and high COVID-19 infection fear groups, and investigated factors associated with COVID-19 infection fear. High COVID-19 infection fear was significantly associated with being a woman and poor professional quality of life. High COVID-19 infection fear group had higher burnout levels and secondary traumatic stress scores than the low and medium fear groups. These findings deepen our understanding of risk factors for and psychological outcomes of COVID-19 infection fear in HCWs.

Effect of Childhood Adversity and Positive Psychological Resources on Stress Response-Comparison Between Depressed and Nondepressed Young Adults.

Objective: The purpose of this study was to explore the relationship between stress response, childhood adversity, and positive psychological resources in young adults, to investigate the mediation effect of positive psychological resources, and to compare the moderated mediation effects between depressed and non-depressed groups. Methods: A total of 360 young adults (165 outpatients diagnosed with depression and 195 non-depressed participants) were recruited. Data were collected using the Adverse Childhood Events questionnaire, Positive Resources Test, and Stress Response Inventory. Models 4 and 14 of the PROCESS macro were used to test the mediating and moderated mediating effects. Results: In both groups, the stress response was negatively correlated with positive psychological resources and positively correlated with childhood adversity. Positive psychological resources mediated childhood adversity and depression. In the depression group, positive resources had a moderated mediation effect on the relationship between childhood adversity, positive psychological resources, and stress response. Conclusion: The findings suggest the importance of enhancing positive psychological resources, especially in patient groups, to help overcome childhood adversity and cope with stress more effectively.

Nucleophilic covalent ligand discovery for the cysteine redoxome.

With an eye toward expanding chemistries used for covalent ligand discovery, we elaborated an umpolung strategy that exploits the 'polarity reversal' of sulfur when cysteine is oxidized to sulfenic acid, a widespread post-translational modification, for selective bioconjugation with C-nucleophiles. Here we present a global map of a human sulfenome that is susceptible to covalent modification by members of a nucleophilic fragment library. More than 500 liganded sulfenic acids were identified on proteins across diverse functional classes, and, of these, more than 80% were not targeted by electrophilic fragment analogs. We further show that members of our nucleophilic fragment library can impair functional protein-protein interactions involved in nuclear oncoprotein transport and DNA damage repair. Our findings reveal a vast expanse of ligandable sulfenic acids in the human proteome and highlight the utility of nucleophilic small molecules in the fragment-based covalent ligand discovery pipeline, presaging further opportunities using non-traditional chemistries for targeting proteins.

Chaperone-directed ribosome repair after oxidative damage.

Because of the central role ribosomes play for protein translation and ribosome-mediated mRNA and protein quality control (RQC), the ribosome pool is surveyed and dysfunctional ribosomes degraded both during assembly, as well as the functional cycle. Oxidative stress downregulates translation and damages mRNAs and ribosomal proteins (RPs). Although damaged mRNAs are detected and degraded via RQC, how cells mitigate damage to RPs is not known. Here, we show that cysteines in Rps26 and Rpl10 are readily oxidized, rendering the proteins non-functional. Oxidized Rps26 and Rpl10 are released from ribosomes by their chaperones, Tsr2 and Sqt1, and the damaged ribosomes are subsequently repaired with newly made proteins. Ablation of this pathway impairs growth, which is exacerbated under oxidative stress. These findings reveal an unanticipated mechanism for chaperone-mediated ribosome repair, augment our understanding of ribosome quality control, and explain previous observations of protein exchange in ribosomes from dendrites, with broad implications for aging and health.

The Change of Suicidal Ideation Over a 12-Week Naturalistic Treatment of Depression: Comparison Between Young People and Older Adults.

OBJECTIVE: We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants. METHODS: A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13-24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups. RESULTS: At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group. CONCLUSION: These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

Sex Differences in COVID-19 Infection Fear in a Community Sample of Korean Adults Using Quantile Regression.

This study aims to explore the impact of distributional changes in coronavirus disease 2019 (COVID-19) infection fear with sex differences. A quota sampling strategy was followed and 483 Korean adults were surveyed in a community sample. Self-report questionnaires were used to assess COVID-19 infection fear, depressive symptoms, and general characteristics. Quantile regression was used to explore the regression relationship of COVID-19 infection fear and an individual's sex. There was a significant difference in COVID-19 infection fear (P = 0.001) and depression (P = 0.008) between the sexes - male and female. The differences between sexes at the 20th and 30th percentiles were significant (ß = 2.04, P = 0.006; ß = 1.5, P = 0.004, respectively). The results demonstrate that sex significantly predicts COVID-19 infection fear and women had significantly greater fear than men in the mild-level of COVID-19 infection fear.

Aryloxypropanolamine targets amyloid aggregates and reverses Alzheimer-like phenotypes in Alzheimer mouse models.

BACKGROUND: Aggregated amyloid-ß (Aß) is considered a pathogenic initiator of Alzheimer's disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aß is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aß aggregates. METHODS: The dissociative activity of aryloxypropanolamine derivatives against Aß aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. RESULTS: Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against ß-sheet-rich Aß aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular ß-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aß. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aß and tau. CONCLUSIONS: Collectively, our results evince the potential of chemical-driven dissociation of Aß aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

COVID-19-Related Functional Impairment in a Community Sample of Korean Adults: Associations With Depression, COVID-19 Infection Fear, and Resilience.

OBJECTIVE: We aimed to determine the effects of depression, COVID-19 infection fear, and resilience on COVID-19-related functional impairment. METHODS: We obtained data from 476 community-dwelling adults aged 20-69 years living in Jeju, South Korea, and evaluated the relationships between COVID-19-related functional impairment (work/school, social, and home life) and sociodemographic and healthrelated characteristics, COVID-19-related life changes (financial difficulties since the pandemic, employment change, interpersonal conflict), and clinical characteristics, including depression, COVID-19 infection fear, and resilience. RESULTS: Functional impairment in the home life domain was associated with marital status and monthly income. Greater work/school, social, and home life functional impairment was significantly associated with all COVID-19-related life changes. Regression analysis indicated that resilience modulated the positive associations of COVID-19-related functional impairment with symptoms of depression and COVID-19 infection fear when relevant factors were controlled for. CONCLUSION: Our results suggest the importance of clinical characteristics, including depression, COVID-19 infection fear, and resilience for understanding functional impairment related to COVID-19. These results have important implications for interventions aimed at reducing depression and COVID-19 infection fear, and enhancing resilience.

[Do parenting stress, work-family conflict, and resilience affect retention intention in Korean nurses returning to work after parental leave?: a cross-sectional study]. / 육아휴직 후 복직 간호사의 ì–‘ìœ¡ìŠ¤íŠ¸ë ˆìŠ¤, 일-ê°€ì • 갈등, ìžì•„íƒ„ë ¥ì„±ì´ 재직의도에 미치는 영향.

Purpose: This study investigated whether parenting stress, work-family conflict, resilience affect retention intent in Korean nurses returning to work after parental leave. Methods: The participants in this study were 111 nurses recruited from 10 hospitals in Korea, who were working after formal parental leave from their hospitals. Collected data were analyzed using descriptive statistics, the t-test, analysis of variance, the Mann-Whitney U-test, Pearson correlation coefficients, and hierarchical regression. Results: Retention intention (33.80±7.78), parenting stress (101.70±17.57), and resilience (85.02±12.75) were at greater than moderate levels and a midpoint level of work-family conflict (29.63±7.00) was noted in this sample of mostly women nurses in their 30s. The factors affecting retention intent were parental leave duration, the number of times that participants had taken parental leave, health condition, work-family conflict, and resilience. The total explanatory power of these variables was 36.7%. Retention intent had a negative correlation with parenting stress and work-family conflict. Conversely, retention intent was positively correlated with resilience. Conclusion: This study supports the need for flexible adjustment of returning nurses' working hours and family-friendly policies to promote balance between work and family. It is also necessary to develop and apply measures that boost resilience and support health improvement for nurses returning to work.As nurses are often assigned to new areas of work upon return, training programs to aid their adjustment may also be helpful.

Development of Korean Version of PTSD Checklist for DSM-5 (K-PCL-5) and the Short Form (K-PCL-5-S).

OBJECTIVE: This study presents the reliability and validity of the Korean version of the post-traumatic stress disorder (PTSD) checklist for the Diagnostic and Statistical Manual for Mental Disorders-fifth edition (DSM-5) (K-PCL-5) and the short form (K-PCL-5-S). METHODS: Seventy-one subjects with PTSD, 74 subjects with mood or anxiety disorders, and 99 healthy controls were enrolled. The Korean version of the Structured Clinical Interview for DSM-5-research version was used to confirm the presence of PTSD. The Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Impact of Event Scale-Revised (IES-R), and Spielberger State Trait Anxiety Inventory (STAI) were used to evaluate the concurrent validity of the K-PCL-5 and K-PCL-5-S. RESULTS: It presented good internal consistency (Cronbach's α=0.93) and test-retest reliability (r=0.90). The K-PCL-5 and K-PCL-5-S were highly correlated with the BDI-II, BAI, IES-R, STAI-S, and STAI-T. The suggested cutoff score for PTSD was 33 for the K-PCL-5 with a sensitivity of 88.51 and specificity of 89.09, and 6 for the K-PCL-5-S with a sensitivity of 91.95 and specificity of 89.09. The data were best explained with a one-factor model. CONCLUSION: These results demonstrated the good reliability and validity of the K-PCL-5 and K-PCL-5-S, and their suitability as simple tools for PTSD assessment.

Reaction-based fluorogenic probes for detecting protein cysteine oxidation in living cells.

'Turn-on' fluorescence probes for detecting H2O2 in cells are established, but equivalent tools to monitor the products of its reaction with protein cysteines have not been reported. Here we describe fluorogenic probes for detecting sulfenic acid, a redox modification inextricably linked to H2O2 signaling and oxidative stress. The reagents exhibit excellent cell permeability, rapid reactivity, and high selectivity with minimal cytotoxicity. We develop a high-throughput assay for measuring S-sulfenation in cells and use it to screen a curated kinase inhibitor library. We reveal a positive association between S-sulfenation and inhibition of TK, AGC, and CMGC kinase group members including GSK3, a promising target for neurological disorders. Proteomic mapping of GSK3 inhibitor-treated cells shows that S-sulfenation sites localize to the regulatory cysteines of antioxidant enzymes. Our studies highlight the ability of kinase inhibitors to modulate the cysteine sulfenome and should find broad application in the rapidly growing field of redox medicine.

The Moderating Effects of Accurate Expectations of Lethality in the Relationships between Suicide Intent and Medical Lethality on Suicide Attempts.

OBJECTIVE: The purpose of this study was to explore the accuracy of expectation of medical lethality and to identify characteristics related to high medical lethality in suicide attempters. METHODS: A total of 370 suicide attempters (173 men, 197 women) who visited the emergency department at one university hospital were interviewed. RESULTS: Using the Lethality Scale, 103 (27.8%), 114 (30.8%), and 153 (41.4%) suicide attempters were assigned to the low, medium, and high medical lethality groups, respectively. The medium and high medical lethality groups were older, and reported poorer socioenvironmental conditions, compared with the low lethality group. Higher levels of suicide intent were associated with more lethal attempts but only for those attempters who had accurate expectations of the medical lethality of their attempts. CONCLUSION: The accuracy of expectations about the likelihood of dying was found to moderate the relationships between suicide intent and medical lethality.

Relationship between Handgrip Strength and Low-grade Inflammation in Older Adults with Depression.

OBJECTIVE: The relationship among physical functional decline, low-grade inflammation, and depression remains unclear. The aim of this study was to examine the association between hand grip strength (HGS) and high-sensitivity C-reactive protein (hs-CRP) in a large sample with depression. METHODS: This study used data obtained from a representative Korean sample of 9,402 people who participated in the seventh Korean National Health and Nutrition Examination Survey. Physical function was assessed using a digital grip strength dynamometer. Depression was identified using a cutoff of 5 on the Patient Health Questionnaire-9 (PHQ-9), and high hs-CPR level was defined as ≥ 3.0 mg/L. RESULTS: In older adults (≥ 60 years) with depression, 43.8% of those with high hs-CRP levels had low HGS, compared to 21.8% of those with hs-CRP levels < 3.0 mg/L (p = 0.002). Multivariate analysis revealed that, after adjustments for potentially confounding factors, high hs-CRP was independently associated with lower HGS (B = -2.25; 95% confidence interval = -4.49 to -0.02) in older adults with depression, but not in younger or middle-aged adults with depression. CONCLUSION: These findings suggest a significant correlation between physical functional decline and low-grade inflammation in older adults with depression.

Association between discrepancy in objective and subjective cognitive abilities and treatment response in patients with major depressive disorder: A CAN-BIND-1 study report.

BACKGROUND: Major Depressive Disorder (MDD) is characterized by objective and subjective cognitive deficits. Discrepancies between objective and subjective cognitive performance can reflect under- to over-estimations of cognitive abilities, and these discrepancies are referred to as cognitive self-appraisals. Despite evidence that low self-appraisals are associated with depression, the modifiability of self-appraisals and their association with treatment outcome remains unclear. The current study examined whether self-appraisals change following antidepressant treatment. Furthermore, we investigated the association of self-appraisals with treatment outcome. METHODS: As part of the CAN-BIND-1 clinical trial, 154 patients with MDD completed measures of objective and subjective cognitive abilities, depressive symptoms, and functional outcomes (work productivity, psychosocial functioning, and quality of life) at baseline and post-escitalopram treatment. Self-appraisals were calculated based on discrepancies between objective and subjective cognitive abilities, with higher scores indicating overestimation of cognitive abilities. RESULTS: Baseline self-appraisals were not predictive of treatment outcomes. However, self-appraisals increased from pre- to post-treatment. Moreover, pre-post treatment increases in self-appraisals were associated with positive treatment response and remission, decreases in depressive symptoms, and improvements in work productivity, psychosocial functioning, and quality of life. LIMITATIONS: The pre-post intervention design precluded examining the temporal precedence of change in self-appraisals versus depressive symptoms and functional outcomes. CONCLUSIONS: Findings are the first to demonstrate that self-appraisals are treatment-sensitive and are associated with treatment outcomes and recovery from MDD. Cognitive self-appraisals may represent a key marker of treatment response and a valuable target for assessment and intervention, as well as a potential mechanism underlying risk and recovery.

Factors Associated With Health-Related Quality of Life Among Older People Exposed to the Jeju 4·3 Incident.

OBJECTIVE: We explored factors associated with health-related quality of life (HRQOL), including socio-demographic and clinical characteristics, in among older people exposed to the Jeju 4·3 incident, and aimed to determine the effects of depression, posttraumatic stress disorder (PTSD) and perceived social support on HRQOL. METHODS: We obtained data from 110 survivors and 1,011 immediate family members of the victims of the Jeju April 3 incident (mean age, 75.1 years), and evaluated the relationships of HRQOL with sociodemographic and clinical characteristics including posttraumatic and depressive symptoms, and perceived social support. RESULTS: Poorer physical health, psychological health, social relationships, and environment HRQOL domain scores were strongly associated with older age, being a woman, poor socioeconomic status, and symptoms of depression and PTSD. The regression analyses indicated that, when relevant factors were controlled for, perceived social support moderated the negative association between HRQOL and psychiatric symptoms. CONCLUSION: Our results suggest the importance of sociodemographic characteristics, in addition to psychiatric symptoms, for understanding HRQOL in older people exposed to the Jeju 4·3 incident. These results have important implications for interventions aiming to improve the HRQOL of the victims of the Jeju 4·3 incident.