Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:To explore the characteristics of hippocampal subfield volume changes in bipolar disorder (BD) patients with childhood trauma and investigate the correlation between these volume changes and the severity of depressive symptoms.Methods:A total of 112 BD patients in the depressive phase and 62 healthy controls (HC) were recruited from April 2019 to April 2024. All participants were assessed using 17-item Hamilton depression scale (HAMD-17), Hamilton anxiety scale (HAMA), and the childhood trauma questionnaire (CTQ). Based on CTQ scores, BD patients were divided into two groups: the BD with childhood trauma group (BD-CT group, n=51) and the BD without childhood trauma group (BD-nCT group, n=61). T1-weighted magnetic resonance imaging (MRI) scans of the brain were collected for all participants, and hippocampal subfield volumes were segmented using FreeSurfer software.SPSS 26.0 software and Rv 4.1.1 software were used for data analysis.Generalized linear models were used to compare volume differences among three groups. Partial correlation analysis was performed to examine the relationship between the hippocampal subfield volumes showing significant differences and HAMD scores. Results:Significant differences were observed among the three groups in the left CA3(221.49(185.83, 243.02), 194.02(163.53, 226.19), 227.39(200.65, 247.47)), left CA4(261.68(240.89, 285.45), 236.86(210.76, 264.78), 269.75(244.90, 286.03)), left granule cell layer of the dentate gyrus (GC-ML-DG)(307.84(283.35, 328.85), 277.92(249.51, 308.25), 315.39(285.18, 330.25)), and left molecular layer(586.72(549.38, 635.25), 548.16(500.34, 605.24), 602.15(557.63, 637.13)) (Wald χ2=12.81-17.60, all P<0.05). The BD-CT group had significantly smaller volumes in the left CA3, left CA4, left GC-ML-DG, and left molecular layer compared to the BD-nCT group (all P<0.05). The BD-CT group also showed significantly smaller volumes in the left CA3, left CA4, and left GC-ML-DG compared to the HC group (all P<0.05). The volumes of left CA3 ( r=-0.33), left CA4 ( r=-0.31), left GC-ML-DG ( r=-0.31), and left molecular layer ( r=-0.28) regions were negatively correlated with HAMD scores (all P<0.05, Bonferroni correction). Conclusion:BD patients with childhood trauma exhibit reduced volumes in the left hippocampus subfields, including left CA3, left CA4, left GC-ML-DG and left molecular layer.These volume reductions are negatively correlated with the severity of depression.

Objective:To explore the characteristics of hippocampal subfield volume changes in bipolar disorder (BD) patients with childhood trauma and investigate the correlation between these volume changes and the severity of depressive symptoms.Methods:A total of 112 BD patients in the depressive phase and 62 healthy controls (HC) were recruited from April 2019 to April 2024. All participants were assessed using 17-item Hamilton depression scale (HAMD-17), Hamilton anxiety scale (HAMA), and the childhood trauma questionnaire (CTQ). Based on CTQ scores, BD patients were divided into two groups: the BD with childhood trauma group (BD-CT group, n=51) and the BD without childhood trauma group (BD-nCT group, n=61). T1-weighted magnetic resonance imaging (MRI) scans of the brain were collected for all participants, and hippocampal subfield volumes were segmented using FreeSurfer software.SPSS 26.0 software and Rv 4.1.1 software were used for data analysis.Generalized linear models were used to compare volume differences among three groups. Partial correlation analysis was performed to examine the relationship between the hippocampal subfield volumes showing significant differences and HAMD scores. Results:Significant differences were observed among the three groups in the left CA3(221.49(185.83, 243.02), 194.02(163.53, 226.19), 227.39(200.65, 247.47)), left CA4(261.68(240.89, 285.45), 236.86(210.76, 264.78), 269.75(244.90, 286.03)), left granule cell layer of the dentate gyrus (GC-ML-DG)(307.84(283.35, 328.85), 277.92(249.51, 308.25), 315.39(285.18, 330.25)), and left molecular layer(586.72(549.38, 635.25), 548.16(500.34, 605.24), 602.15(557.63, 637.13)) (Wald χ2=12.81-17.60, all P<0.05). The BD-CT group had significantly smaller volumes in the left CA3, left CA4, left GC-ML-DG, and left molecular layer compared to the BD-nCT group (all P<0.05). The BD-CT group also showed significantly smaller volumes in the left CA3, left CA4, and left GC-ML-DG compared to the HC group (all P<0.05). The volumes of left CA3 ( r=-0.33), left CA4 ( r=-0.31), left GC-ML-DG ( r=-0.31), and left molecular layer ( r=-0.28) regions were negatively correlated with HAMD scores (all P<0.05, Bonferroni correction). Conclusion:BD patients with childhood trauma exhibit reduced volumes in the left hippocampus subfields, including left CA3, left CA4, left GC-ML-DG and left molecular layer.These volume reductions are negatively correlated with the severity of depression.

OBJECTIVETo downregulate the expression of pituitary tumor transforming gene 1 (PTTG1) in osteosarcoma (OS) cells by siRNA technology and to investigate related biological impact on cell proliferation, cell cycle and cell invasion of OS.

METHODSThree OS cell lines and osteoblast hFOB1.19 cell line were used in this study. Control siRNA and PTTG1 siRNA were employed to transfect OS U2OS cells, and PTTG1 protein level was detected by Western blot after the transfection. Effects of PTTG1 siRNA on cell proliferation, cell cycle and cell invasion were investigated by CCK-8, flow cytometry and Boyden chamber, respectively. Finally, activity of Akt and its downstream target gene expression were analyzed by Western blot in U2OS cells upon various treatments.

RESULTSExpression of PTTG1 protein in 3 OS cells (MG-63, SaOS-2 and U2OS) was significantly higher than that in osteoblast hFOB1.19, among which U2OS cells displayed the highest level. PTTG1 siRNA markedly downregulated the expression of PTTG1 protein in U2OS cells, leading to obvious inhibition of cell proliferation, altered cell cycle distribution and reduced ability of invasion of U2OS cells. Moreover, downregulation of PTTG1 reduced the expression of p-Akt (S473 and T308), MMP-2 and MMP-9 proteins, along with enhanced expression of p21 and E-cadherin proteins.

CONCLUSIONSPTTG1 may be tightly linked to the development of OS and therefore may serve as a novel target for precision therapy of OS.

Bone Neoplasms ; metabolism ; pathology ; Cadherins ; metabolism ; Cell Cycle ; drug effects ; physiology ; Cell Movement ; Cell Proliferation ; drug effects ; physiology ; Down-Regulation ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; Osteosarcoma ; metabolism ; pathology ; RNA, Small Interfering ; pharmacology ; Securin ; genetics ; metabolism ; Transfection