1.Sex-specific Serum Biomarker Associations with Antidepressant Treatment Outcomes in Depressive Disorders
Jae-Min KIM ; Hee-Ju KANG ; Ju-Wan KIM ; Min JHON ; Min-Gon KIM ; Ju-Yeon LEE ; Sung-Wan KIM ; Il-Seon SHIN
Clinical Psychopharmacology and Neuroscience 2026;24(1):106-117
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.
2.Alterations of Cortical Thickness in High Suicidality Patients with Panic Disorder and Their Relationship with Symptomatology and Treatment Response
Ji-Yoon HAM ; Hyun-Ju KIM ; Yeong-Geon HWANG ; Tai-Kiu CHOI ; Ji-Eun KIM ; Sang-Hyuk LEE
Clinical Psychopharmacology and Neuroscience 2026;24(1):93-105
Objective:
Patients with panic disorder (PD) are approximately four times more likely to experience suicidal thoughts and attempts compared to healthy controls (HCs). Despite the elevated risk compared to HCs, the relationship between cortical thickness (CT) in PD and suicidality remains underexplored.
Methods:
We recruited 161 right-handed participants, including 82 PD patients and 79 HCs, and assessed them using a comprehensive battery of psychological scales, including the Scale for Suicidal Ideation (SSI), Early Trauma Inventory Self Report-Short Form, Neuroticism-Extraversion-Openness Personality Inventory-Neuroticism (NEO-N), State-Trait Anxiety Inventory-Trait Anxiety (STAI-T), Panic Disorder Severity Scale (PDSS), and Beck Depression Inventory.
Results:
In whole-brain vertex-wise group comparison, patients with PD demonstrated significantly lower CT values in the insula, lateral occipital sulcus, and precentral gyrus compared to HCs. Notably, paradoxical significant positive correlations were observed between SSI total scores and CT in the above-mentioned regions within the PD cohort.Pearson’s correlation analyses further indicated that CT in these regions may be linked to high levels of early trauma, trait anxiety (e.g., NEO-N, STAI-T), panic symptom severity (e.g., PDSS), and treatment response in patients with PD.
Conclusion
This study suggest that suicidality in PD may be associated with CT in specific EFN regions related to suicidal brain and that CT in these regions could play a critical role in anxiety symptomatology in PD.
3.Muscle Loss Driven by Extracellular Signal-Regulated Kinase Suppression via β-Adrenergic Activation in High-Normal Catecholamine Status
Jieun LEE ; Ju Yeon KWAK ; Ho Yeop LEE ; Ji Sun MOON ; Hyo Ju JANG ; Ha Thi NGA ; Thi Linh NGUYEN ; Alfin Mohammad ABDILLAH ; Junglyun KIM ; Sihwan KIM ; Yong Ryoul YANG ; Jeong Eun LEE ; Hyon-Seung YI
Endocrinology and Metabolism 2026;41(2):319-332
Background:
Catecholamines play a crucial role in muscle biogenesis, but their persistent elevation is linked to muscle wasting, which is poorly understood. This study aimed to investigate the association between catecholamine levels and age-related muscle loss.
Methods:
This retrospective study evaluated the plasma levels of two catecholamines, metanephrine and normetanephrine, and the clinical characteristics of 830 patients with adrenal incidentaloma on computed tomography (CT). Cross-sectional CT data at the L3 lumbar vertebrae were used to measure muscle areas. In vitro studies on C2C12 myotubes were conducted to examine β-adrenergic receptor signaling pathways and their role in myogenesis.
Results:
Men had significantly higher mean metanephrine levels of 0.17 nmol/L and normetanephrine levels of 0.63 nmol/L than women (P<0.05). Total abdominal muscle area was negatively correlated with catecholamine levels in both men and women, with the strongest negative correlation between normetanephrine levels and total abdominal muscle area in men (r=–0.31, P<0.001). Similarly, the strongest negative correlation between visceral fat area and metanephrine was observed in men (r=–0.25, P=0.004). Clenbuterol, a β-adrenergic receptor agonist, inhibited myogenesis, including myotube formation by extracellular signal-regulated kinase (ERK) suppression in C2C12 myoblasts. Conversely, β-blockers increased myogenesis via increasing ERK phosphorylation in C2C12 cells. These findings suggest that β-adrenergic modulation influences skeletal muscle differentiation, with ERK phosphorylation.
Conclusion
Catecholamine levels are associated with age, sex, muscle mass, and fat mass. Monitoring catecholamine levels, particularly in older men and in individuals with reduced muscle mass, may help manage age-related muscle loss and lead to individualized treatment strategies.
4.Evaluation of gestational age by pregnancy outcomes and distribution of pregnancy-related codes in Korean claims data
Woo-Jung KIM ; Yunha NOH ; Yongtai CHO ; Eun-Young CHOI ; HyunJoo LIM ; Hyesung LEE ; Ju-Young SHIN
Epidemiology and Health 2026;48(1):e2026007-
OBJECTIVES:
This study aimed to evaluate a fixed-duration algorithm for gestational age (GA) estimation according to pregnancy outcomes and to describe the GA distribution of pregnancy-related codes in Korea.
METHODS:
We included 351,055 pregnancy episodes (2019–2022) from linked data between the National Health Insurance Service and the Korea Immunization Registry Information System (KIRIS). GA from claims data was estimated by subtracting fixed durations from the delivery date (algorithm-based GA), and GA derived from KIRIS was defined as the gold standard. Accuracy was evaluated as the proportion of episodes in which the difference between the estimated GA and the reference standard fell within ±2 weeks. We described the distributions of the GA at which each prenatal test, pregnancy complication, and diagnostic code was recorded.
RESULTS:
Algorithm-based GA estimation showed high accuracy for live births (92.2% within ±2 weeks) but markedly lower accuracy for non-live birth outcomes, including stillbirth (3.3%), termination (7.2%), spontaneous abortion (45.2%), and ectopic pregnancy (20.0%). In additional analyses aimed at identifying potential indicators for improving GA estimation, most events occurred within clinically expected timeframes, although some individual codes exhibited poor temporal alignment.
CONCLUSIONS
Algorithm-based GA estimation using claims data performed well for live births but demonstrated limited accuracy for non-live birth outcomes. Incorporating information from prenatal tests and pregnancy complications may enhance GA estimation.
5.The association between the consumption of raw Kudoa septempunctata–infected farmed Paralichthys olivaceus and gastrointestinal symptoms
Jihye AN ; En-Joo JUNG ; Soon-Ok LEE ; Jong-Hoon CHOI ; JungHee KIM ; Sung-Jong HONG ; Sung-Hee HONG ; Jung-Won JU ; Hyungjun KIM ; Kwang-Pil KO
Epidemiology and Health 2026;48(1):e2026003-
OBJECTIVES:
Kudoa septempunctata has been identified as the causative agent of food poisoning following the consumption of raw farmed Paralichthys olivaceus. However, cohort studies providing robust evidence for an association between K. septempunctata and gastrointestinal symptoms remain limited. This prospective cohort study investigated the association between the consumption of K. septempunctata–infected farmed P. olivaceus and the occurrence of gastrointestinal symptoms.
METHODS:
Individuals who purchased raw farmed P. olivaceus between 2020 and 2021 were selected as the study population. Study data included 2 rounds of questionnaire surveys administered before and after consumption, 2 muscle specimens obtained from each purchased fish, and human biological specimens collected from individuals who developed gastrointestinal symptoms within 24 hours after consumption. Data were analyzed using the chi-square test and t-test, and the association between consumption of K. septempunctata–infected farmed P. olivaceus and gastrointestinal symptoms was evaluated using relative risk estimates between exposure groups.
RESULTS:
The relative risk of gastrointestinal symptoms associated with exposure to K. septempunctata–infected P. olivaceus ranged from 71.2 (95% confidence interval [CI], 27.0 to 178.6) to 124.5 (95% CI, 43.5 to 355.0) across the 2 case definitions. A strong and statistically significant association was observed between exposure to K. septempunctata–infected P. olivaceus and the development of acute gastrointestinal symptoms.
CONCLUSIONS
These findings indicate both an association and a causal relationship between consumption of K. septempunctata–infected farmed P. olivaceus and the onset of gastrointestinal symptoms.
6.Acute Heart Failure Across the Ejection Fraction Spectrum: Phenotypes, Management, and Outcomes From Nationwide KorHF III Registry
Huijin LEE ; Eung Ju KIM ; Seong Woo HAN ; Seong-Mi PARK ; Hyung-Seop KIM ; Myung-Chan CHO ; Hyo-Suk AHN ; Mi-Seung SHIN ; Seok-Jae HWANG ; Jin-Ok JEONG ; Dong Heon YANG ; Junho HYUN ; Jin Oh CHOI ; Hae-Young LEE ; Byung-Su YOO ; Seok-Min KANG ; Dong-Ju CHOI ; Hyun-Jai CHO ;
International Journal of Heart Failure 2026;8(1):43-55
Background and Objectives:
Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort.
Methods:
The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs).
Results:
Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective.
Conclusions
Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.
7.Development of Korean Standardized Heart Failure Registry: Experience From Integration of KorAHF and KorHF III
Eui-Soon KIM ; Huijin LEE ; Jong-Chan YOUN ; Byung-Su YOO ; Hae-Young LEE ; Ju-Hee LEE ; Dong-Hyuk CHO ; Mi-Hyang JUNG ; Hye Sun LEE ; Hyun-Jai CHO
International Journal of Heart Failure 2026;8(1):1-11
Heart failure (HF) prevalence and associated socio-economic costs have risen rapidly in Korea, creating urgent demand for a national, standardized prospective registry to support quality monitoring, outcome comparison, and real-world evidence. Standardized data definitions are essential for valid comparisons across studies and healthcare settings. We created a unified national HF cohort by integrating the two largest Korean registries, KorAHF (2011–2014;n=5,625) and KorHF III (2018–2023; n=7,351), yielding 12,976 hospitalized HF patients. Because heterogeneous variable definitions impeded direct comparisons, we implemented a harmonization pipeline across demographic, clinical, imaging, biomarker, therapeutic, and outcome domains, aligned with international standards and reinforced by systematic data quality checks.A multidisciplinary panel then conducted a structured decision process to produce the Korean HF Standard Dataset, a tiered and interoperable variable set spanning six domains: demographics, presentation at admission, in-hospital events and comorbidities, discharge status, outpatient follow-up, and readmission events. This integrated platform and standardized variables enable precise identification of HF patient phenotypes and prognostic factors, establishing an evidence-based foundation for disease management. This supports an analysis of temporal changes in treatment patterns and outcomes, generates data to inform future clinical practice guidelines, and provides a practical basis for planning large, continuous, prospective HF registries. Furthermore, it also facilitates pragmatic, registry-based randomized clinical trials and unmet-needs assessments that can guide national health policy. Establishing a foundation for future linkage with national health databases, this platform will allow for enhanced accuracy, comparability, and representativeness, powering quality improvement initiatives and population-level monitoring of Korea’s growing HF burden.
8.Awareness, Diagnostic Approaches, and Management of Heart Failure in Korea: A Nationwide Survey Comparing Primary Care Physicians and Cardiology Specialists
Sunki LEE ; Min Gyu KONG ; Mi-Hyang JUNG ; Hack-Lyoung KIM ; Jae Hyuk CHOI ; Jin Oh NA ; Yang Hyun CHO ; Dong-Ju CHOI ; Eung Ju KIM
International Journal of Heart Failure 2026;8(1):76-88
Background and Objectives:
Heart failure (HF) imposes a significant global burden, yet awareness and implementation of guideline-directed management remain suboptimal. This study evaluated HF awareness, diagnostic patterns, and therapeutic strategies among physicians in Korea.
Methods:
A nationwide online survey was conducted from July to August 2019, targeting primary care physicians (PCPs; n=8,000) and hospital-based cardiology specialists (n=1,339) across Korea. The questionnaire comprised 23 items covering baseline characteristics, perceptions of HF prognosis, diagnostic approaches, and treatment practices.
Results:
A total of 543 physicians responded (209 PCPs and 334 cardiology specialists). While the majority correctly defined HF, a substantial proportion underestimated the lifetime risk and poor prognosis. Cardiology specialists were more likely than PCPs to use objective diagnostic tools, including echocardiography (97% vs. 61%, p<0.001) and natriuretic peptide testing (90% vs. 57%, p<0.001). Among PCPs, 29% reported diagnosing HF based on symptoms and physical findings without objective testing, and 27% reported referring patients to general hospitals for diagnostic evaluation. Prescription rates for guideline-directed medical therapies, including renin-angiotensin system blockers and beta-blockers, were consistently higher among cardiology specialists.PCPs more frequently cited advanced age as a barrier to prescribing evidence-based medications.
Conclusions
Physicians’ awareness and clinical practices regarding HF in Korea remain suboptimal. Given the growing burden, high mortality, and substantial costs of HF, early detection, appropriate diagnostic evaluation, and timely referral are essential. Targeted education and system-level strategies to improve guideline implementation, particularly in primary care settings, are warranted.
9.Risk Factors and Clinical Characteristics of Graves’ Ophthalmopathy: a Retrospective Multicenter Study in Korea
Yoon Young CHO ; Hyunju PARK ; Jung HEO ; Jiyeon AHN ; Min Kyung LEE ; Jae Hyuk LEE ; Ju-Yuen LEE ; Yun Jin KIM ; Seo Young SOHN
International Journal of Thyroidology 2026;19(1):85-94
Background and Objectives:
Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disorder that can adversely affect quality of life in patients with Graves’ disease (GD). The objective of this study was to characterize the clinical features of patients with GO and to identify risk factors associated with its development and the need for anti-inflammatory treatment.
Materials and Methods:
In this multicenter, retrospective observational study, 818 patients with GD were identified via electronic medical record review. Clinical characteristics were assessed, and logistic regression analyses were performed to identify risk factors for GO development and the need for anti-inflammatory treatment.
Results:
Among the 818 patients with GD, 135 (16.5%) developed GO, and 60 (7.3%) of these patients received anti-inflammatory treatment. GO was diagnosed at the time of GD diagnosis in 54.8% of cases, and proptosis and eyelid/orbital swelling were the common presenting features. In multivariable analysis, female sex (odds ratio [OR]: 1.75, confidence interval [CI]: 1.02-3.03), goiter (OR: 1.71, CI: 1.08-2.71), and smoking (ex-smokers: OR, 2.18; 95% CI: 1.02-4.65; current smokers: OR, 3.11; CI, 1.78-5.44) were independently associated with GO development, whereas diabetes (OR: 0.35, CI: 0.14-0.89) was inversely associated. Higher total cholesterol (OR: 1.31, CI: 1.01-1.04) and elevated thyrotropin-binding inhibitory immunoglobulin levels (OR: 1.07, CI: 1.02-1.11) were also significantly associated with the need for anti-inflammatory treatment.
Conclusion
This study delineated the clinical features of GO and identified risk factors for its development and the need for anti-inflammatory treatment in patients with GD, providing valuable information for the management of GO in Korean patients.
10.Fatty Acid-Sensing G Protein-Coupled Receptors in Skeletal Metabolism
Hyun-Ju KIM ; Dong-Kyo LEE ; Xiangguo CHE ; Sihoon LEE ; Je-Yong CHOI
Journal of Bone Metabolism 2026;33(1):1-17
G protein-coupled receptors (GPCRs), commonly known as seven-transmembrane domain receptors, represent one of the largest and most functionally diverse families of membrane receptors. These receptors mediate cellular responses to external signals, thereby influencing various physiological processes. Recent studies have increasingly highlighted the importance of GPCRs in skeletal health, particularly in regulating bone metabolism and the pathogenesis of bone diseases, such as osteoporosis and osteoarthritis. Among GPCRs, a specific subset that responds to fatty acids, including GPR40, GPR120, GPR41, GPR43, GPR84, and GPR119, has received significant attention for its role in skeletal homeostasis. Acting as lipid sensors, these receptors detect changes in fatty acid availability and transduce signals that modulate the differentiation, function, and survival of key bone cell populations, including osteoclasts, osteoblasts, and chondrocytes. This review provides a comprehensive overview of the current understanding of fatty acid-sensing GPCRs in skeletal metabolism, highlighting their potential as novel therapeutic targets for metabolic bone diseases.

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