Objective: This study examined whether baseline levels of 14 serum biomarkers predicted antidepressant remission differently by sex at 12 weeks and 12 months. Methods: In a prospective cohort, 1,086 outpatients with depressive disorders received stepwise antidepressant treatment following a naturalistic protocol. Baseline serum samples were analyzed for biomarkers from six systems: immune (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-4, interleukin-10), metabolic (leptin, ghrelin, total cholesterol), neurotrophic (brain-derived neurotrophic factor), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine). Remission, defined as a Hamilton Depression Rating Scale scores ≤ 7, was assessed at 12 weeks and 12 months. Logistic regression models with biomarker-by-sex interaction and stratified analyses were used, adjusting for clinical covariates. Results: Higher baseline serotonin predicted 12-week remission in males but not in females. At 12 months, lower leptin and higher folate predicted remission only in males, while lower cortisol predicted remission only in females. These showed significant biomarker-sex interactions. No sex-specific interactions were found for immune markers. Conclusion Baseline serum biomarkers across biological systems showed sex-specific associations with treatment outcomes. Neurotransmitter, metabolic, endocrine, and nutritional markers may offer predictive value for sex-tailored, biomarker-informed treatment strategies in depression.

The COVID-19 pandemic has adversely affected the mental health of the global population. This study aimed to assess the acute and persistent symptoms of depression, as well as factors related to their manifestation, through a longitudinal study design. A total of 1,492 community-dwelling adults from an online public panel across three regions were evaluated at baseline, with 908 adults (60.9%) followed up after six months. Depression symptoms were evaluated using Patient Health Questionnaire-9 (PHQ-9). Participants also completed self-administered questionnaires on sociodemographic information, psychosocial experiences related to COVID-19, the UCLA Loneliness Scale, and the Korean version of the Gratitude Questionnaire (K-GQ-6).The prevalence of acute and persistent depression symptoms was 8.4% and 12.0%, respectively. Multivariate logistic regression analysis identified changes in predictors of depression over time, with younger age and self-isolation experience found to be associated with acute depression. Factors such as underlying mental illness, eating and sleeping disturbances, loneliness, and COVID-19-related stress emerged as significant risk factors for persistent depression. A disposition toward gratitude was identified as a protective factor for persistent depressive symptoms. These findings suggest that during any long-term pandemic crisis such as COVID-19, timely support and attention are essential for vulnerable populations, including young people and individuals with mental health conditions, to prevent depression. Specifically, promoting daily routines such as regular eating and sleeping patterns, and managing COVID-19-related stress may be critical in preventing persistent depression. Additionally, psychological support that reduces loneliness and fosters gratitude may help mitigate depression risk.

Objectives: This study aimed to investigate the impact of behavioral and psychological symptoms (BPS), assessed by the neuropsychiatric inventory (NPI) total score, on instrumental activities of daily living (IADL) performance in patients with mild cognitive impairment. Methods: Ninety-two patients diagnosed with mild cognitive impairment who visited a university hospital dementia clinic were recruited. Assessments included the Korean version-Mini Mental State Examination, NPI, Korean-IADL (KIADL), and Short Form of Geriatric Depression Scale-Korean version. Correlation and hierarchical multiple regression analyses were performed to analyze the relationship between BPS and IADL. Results: The mean age of participants was 74.61±5.86 years. K-IADL scores significantly correlated with age (r=0.347, p<0.001) and NPI total score (r=0.265, p<0.05). Hierarchical regression analysis showed that the addition of the NPI total score significantly increased the explained variance of functional decline (R 2 =0.197, F=5.332, p<0.001), with age (β=0.354, p<0.001) and NPI total score (β=0.248, p<0.05) identified as independent predictors in patients with mild cognitive impairment. Conclusions The overall severity of BPS exerts a detrimental effect on IADL function in mild cognitive impairment patients, independent of age and cognitive status. These results underscore the clinical importance of evaluating the cumulative burden of BPS to predict functional prognosis and implement early interventions.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Objective: Stigma influences perceptions of mental illness and novel diseases like coronavirus disease-2019 (COVID-19), often impeding healthcare access despite advancements in medical treatment. This study compares the stigma associated with COVID-19 and mental illness to identify factors that could help reduce stigma. Methods: An online survey was conducted in May 2023 among 1,500 participants aged 19 to 65 in South Korea, using a panel from Embrain, an online survey service. The survey assessed stigma and distress related to COVID-19 and mental illness using a validated questionnaire. It collected demographic and clinical data, evaluated COVID-19-related stigma, fear, and knowledge, and measured prejudice and attitudes toward psychiatric treatment. Personality traits were assessed using the Big Five Inventory (BFI)-10. Factors significantly associated with stigma scores were entered into linear regression analysis. Results: COVID-19-related stigma scores were significantly negatively correlated with knowledge of COVID-19 and positively correlated with fear of infection and age. Individuals with a history of COVID-19 infection had significantly lower scores on COVID-19-related stigma. Similarly, mental illness stigma was negatively correlated with knowledge of psychiatric treatment and positively correlated with age, as well as conscientiousness and neuroticism in the BFI. Personal experience with individuals with mental illness was associated with significantly lower stigma scores. Conclusion This study suggests that the mechanism-making stigma was similar in cases of traditional mental illness and a novel infectious disease. Both cognitive and experiential factors influence stigma. Educating the public about the disease and enabling interactions with affected individuals emerge as effective strategies for stigma reduction.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD). Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5.Logistic regression analyses were conducted. Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education. Conclusion The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation. Methods: This study analyzed data from the 2014 and 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes, using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS. Results: Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients=0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS. Conclusion Nutritional intake was found to not be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.