https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/559 Fri, 26 Dec 2025 13:21:05 GMT 2025-12-26T13:21:05Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78778 Title: Resting-state functional connectivity of the fronto-limbic and default mode network as neural correlates of antidepressant response in major depressive disorder Authors: Kang, Youbin; Jung, Jeyoung; Han, Kyu-Man; Auer, Dorothee P.; Ham, Byung-Joo Abstract: Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, yet antidepressant response remains highly variable, with many patients failing to achieve remission. Resting-state functional connectivity (RSFC) studies have linked MDD to large-scale brain network dysregulation, but methodological inconsistencies and limited focus on treatment response have hindered clinical translation. Methods: We conducted a resting-state fMRI study as part of an 8-week antidepressant trial on 86 patients with MDD and 93 healthy controls (HCs). Utilizing a seed-to-voxel approach based on prior studies of neural networks implicated in antidepressant response, we examined RSFC patterns associated with treatment outcomes. Additionally, we explored their relationships with cognitive function and depressive severity to elucidate neural mechanisms underlying treatment response. Results: Compared to the non-responder group, antidepressant responders exhibited significantly higher ROI-to-ROI FC between the posterior cingulate cortex (PCC) and subgenual anterior cingulate cortex (sgACC), with follow-up seed-to-voxel maps showing higher PCC couplings with the prefrontal cortex, thalamus, and amygdala. In responders, FC between the left amygdala and supramarginal gyrus, and between the ventromedial prefrontal cortex (VMPFC) and lateral occipital cortex, was negatively correlated with cognitive scores. Conversely, in the non-responder group, FC between the left subgenual anterior cingulate cortex (sgACC) and lateral occipital cortex was negatively correlated with digit span but positively with other tasks. FCs involving the amygdala, thalamus, and VMPFC were correlated with depression scale scores. Conclusions: Enhanced connectivity within networks related to emotion regulation, cognitive control, and attention in responders suggests neural mechanisms supporting improved emotional and cognitive flexibility. Sun, 01 Feb 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78778 2026-02-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78320 Title: Childhood trauma and frontal-limbic network abnormalities in major depressive disorder: Resting-state functional connectivity and brain network analysis Authors: Shin, Daun; Jung, Minjee; Park, Jihoon; Kang, Youbin; Ham, Byung-Joo; Auer, Dorothee; Jung, JeYoung; Han, Kyu-Man Abstract: BACKGROUND: Childhood trauma impacts brain development, increasing vulnerability to Major Depressive Disorder (MDD). The frontal-limbic network, essential for emotion regulation and stress response, is frequently implicated in MDD pathophysiology. This study examined whether childhood trauma is associated with alterations in resting-state functional connectivity (FC) within brain networks involved in emotion regulation in individuals with MDD and healthy controls (HCs). METHODS: A cross-sectional study was conducted with 76 patients with MDD and 97 HCs (aged 19-64 years). Resting-state FC was assessed among 24 predefined regions of interest (ROIs) within brain networks associated within the fronto-limbic circuit. Childhood trauma was quantified using the Childhood Trauma Questionnaire (CTQ). ROI-to-ROI FC and global/regional brain network properties were evaluated. RESULTS: The MDD group demonstrated significant reductions in frontal-limbic FC (e.g., left dorsolateral prefrontal cortex [dlPFC]-left hippocampus, left dlPFC-right pregenual anterior cingulate cortex [ACC], right pregenual ACC-right subgenual ACC). Brain network properties analysis revealed a negative correlation between global efficiency and emotional neglect severity, as well as positive correlations between local efficiency/clustering efficiency and total CTQ scores. Specifically, in the MDD group, the clustering coefficient in the ventromedial prefrontal cortex (vmPFC) was positively associated with emotional neglect, whereas in the HC group, total CTQ scores were positively correlated with the nodal degree of the right subgenual ACC. CONCLUSIONS: Childhood trauma is associated with significant alterations in resting-state FC and brain network properties within the frontal-limbic network in individuals with MDD. These findings highlight a potential neural pathway through which early adversity contributes to MDD pathophysiology. Copyright © 2025 Elsevier B.V. All rights reserved. Thu, 01 Jan 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78320 2026-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77988 Title: Identification of chemical scaffolds for targeting ubiquitin-specific protease 11 (USP11) through high-throughput virtual screening Authors: Lee, Hobin; Hurh, Sunghoon; Kang, Soomin; Yoon, Jihwan; Hwang, Jong-Ik; Logan, Derek T.; Kim, Hong-Rae Abstract: USP11 is a promising therapeutic target implicated in Alzheimer's disease and various cancers; however, no specific inhibitors are currently available, with the only known inhibitor being mitoxantrone, which primarily targets topoisomerase II. To identify novel chemical starting points, we conducted high-throughput virtual screening using a USP11 homology model. Screening over 600,000 compounds yielded five structurally distinct hits with significant inhibitory activity. Biochemical validation highlighted two promising scaffolds: benzoxadiazole derivatives and pyrrolo-phenylamidine analogues, both demonstrating structure-dependent inhibition and tractable SAR profiles. Docking studies further characterised their binding modes, supporting their potential for optimisation. Hydroxyphenyl hydrazone analogues raised PAINS-related concerns, while compounds such as squalamine were deprioritized due to weak binding affinity and structural complexity. Overall, this study provides valuable scaffolds and mechanistic insights that can inform future development of potent, selective USP11 inhibitors. Mon, 01 Dec 2025 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77988 2025-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78781 Title: Exploring neurokinin-1 receptor antagonism for depression with structurally differentiated inhibitors Authors: Yoo, Hyeijung; Boo, Kyung-Jun; Nguyen, Lan Phuong; Hwang, Jong-Ik; Lee, Cheol Soon; Yang, Soo Hyun; Jeon, Se Jin; Kim, Hong-Rae; Kim, Hyun Abstract: The neurokinin-1 receptor (NK1R) has been investigated as a potential target for major depressive disorder owing to its role in stress regulation and neuroinflammation. However, clinical trials of NK1R antagonists have yielded inconsistent results, leaving it unclear whether these outcomes reflect limitations of NK1R as a therapeutic target or shortcomings inherent to the clinical candidates tested. The majority of previously developed NK1R antagonists contain a 3,5-bis-trifluoromethylphenyl moiety, which enhances receptor binding but may also influence drug metabolism, pharmacokinetics or receptor interactions, potentially affecting therapeutic efficacy. Whether structurally distinct NK1R antagonists exhibit different antidepressant potential remains an open question. Here we used computational approaches to identify NK1R antagonists lacking the 3,5-bis-trifluoromethylphenyl group and evaluated their effects in preclinical models of depression. Several compounds exhibited NK1R antagonistic activity and reduced depressive-like behaviors, with compound #15 demonstrating the most pronounced effects. Molecular docking and molecular dynamics simulations revealed a distinct binding mode for compound #15, characterized by a hydrogen bond interaction with Asn109 and pi-pi stacking with His197, suggesting structural differences that may influence NK1R modulation. These findings support the potential of structurally diverse NK1R antagonists to modulate behavior and neuroinflammatory responses in preclinical models. While the relevance of these structural differences to clinical outcomes remains to be determined, our results provide a preliminary framework for further investigation of chemically novel NK1R antagonists in the context of major depressive disorder. Sat, 01 Nov 2025 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78781 2025-11-01T00:00:00Z