Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patien...Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patients show only partial or no response to initial or even multiple antidepressant medications and are usually called treatment-resistant depression （TRD） patients. The present work was to measure the features of sensory gating （SG） P50 in TRD patients with the intent of understanding the characteristics of this disease. Methods In 50 TRD patients, 39 non-treatment-resistant depression （NTRD） patients and 51 healthy controls （HC）, auditory evoked potential P50 was measured using the conditioning/testing paradigm presented with auditory double clicks stimuli, and 36 TRD patients had repeated measurements after an 8-week venlafaxine treatment course. Results All the depressive disorder patients, including the TRD and NTRD groups, showed an increased testing stimulus wave （$2-P50） amplitude compared to controls （P 〈0.01 and P 〈0.05）, but there was no significant difference between the TRD and NTRD groups （P 〉0.05）. There were significant differences in the ratio of testing stimulus （S2） and conditioning stimulus （S1） （S2/S1） and in the value of 100 × （1-S2/S1） among the three groups. Compared to the baseline, TRD patients had no significant changes of features and different expression of P50 after acute treatment （P 〉0.05）. Meanwhile, a statistically significant positive correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for Depression （HAMD-17） （P 〈0.01）, and a significantly negative correlation of S1-S2, 100 × （1-S2/S1） with the scores of HAMD-17 （P 〈0.01） were observed in the TRD patients＇ baseline measurement, but there was no correlation after venlafaxine treatment （P 〉0.05）. Conclusions Both the TRD and NTRD patients had obvious SG deficits, with a more severe deficit in TRD patients. Although, with a correlated relationship to the severity of depressive symptoms, SG P50 deficit might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio, S1-S2 and 100 × （1-S2/S1）, was recommended for electrophysiological measurement in TRD patients.展开更多
文摘目的·采用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)探索抑郁症相关的差异基因模块及其枢纽基因,并对差异基因模块进行生物功能注释。方法·在之前对8例抑郁症患者及8名健康对照者(对照组)的外周血mRNA微阵列分析实验的基础上,应用t检验筛选抑郁症患者与对照组的差异表达基因,通过R软件WGCNA包进行分析;当关联系数阈值设定为0.9时,参数β=14,以此构建基因数据集的共表达网络。应用混合动态树切割方法切割网络产生基因模块。采用Pearson相关性检验评估基因模块和抑郁症之间的相关性,分别选取与抑郁症正相关性和负相关性最强的基因模块,并选择模块内连接性最强的前3个基因作为枢纽基因。最后利用GO功能富集分析和KEGG通路分析对2个模块进行功能注释。结果·从16个样品中获得4125个差异表达基因,从中识别出9个基因模块,选择蓝色(blue)模块(R=-0.91,P=0.000)和青色(cyan)模块(R=0.76,P=0.000)进行后续研究。Blue模块的枢纽基因为JAM2(junctional adhesion molecule 2)、SCRN2(secernin 2)和IGHV7-81(immunoglobulin heavy variable 7-81);cyan模块的枢纽基因为SCFD2(Sec1 family domain containing 2)、NR5A2(nuclear receptor subfamily 5 group A member 2)和KCNMA1(potassium calcium-activated channel subfamily M alpha 1)。生物功能注释发现,cyan模块的基因主要富集在胚胎发育、细胞生长、免疫及炎症等生物学过程,blue模块基因则主要在物质加工转运及感染等方面富集。结论·得到2个外周血mRNA基因模块和6个枢纽基因(JAM2、SCRN2、IGHV7-81、SCFD2、NR5A2和KCNMA1),可能与抑郁症显著相关;这2个基因模块可能在胚胎发育、免疫和炎症反应、物质加工转运等方面发挥作用。
文摘Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patients show only partial or no response to initial or even multiple antidepressant medications and are usually called treatment-resistant depression （TRD） patients. The present work was to measure the features of sensory gating （SG） P50 in TRD patients with the intent of understanding the characteristics of this disease. Methods In 50 TRD patients, 39 non-treatment-resistant depression （NTRD） patients and 51 healthy controls （HC）, auditory evoked potential P50 was measured using the conditioning/testing paradigm presented with auditory double clicks stimuli, and 36 TRD patients had repeated measurements after an 8-week venlafaxine treatment course. Results All the depressive disorder patients, including the TRD and NTRD groups, showed an increased testing stimulus wave （$2-P50） amplitude compared to controls （P 〈0.01 and P 〈0.05）, but there was no significant difference between the TRD and NTRD groups （P 〉0.05）. There were significant differences in the ratio of testing stimulus （S2） and conditioning stimulus （S1） （S2/S1） and in the value of 100 × （1-S2/S1） among the three groups. Compared to the baseline, TRD patients had no significant changes of features and different expression of P50 after acute treatment （P 〉0.05）. Meanwhile, a statistically significant positive correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for Depression （HAMD-17） （P 〈0.01）, and a significantly negative correlation of S1-S2, 100 × （1-S2/S1） with the scores of HAMD-17 （P 〈0.01） were observed in the TRD patients＇ baseline measurement, but there was no correlation after venlafaxine treatment （P 〉0.05）. Conclusions Both the TRD and NTRD patients had obvious SG deficits, with a more severe deficit in TRD patients. Although, with a correlated relationship to the severity of depressive symptoms, SG P50 deficit might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio, S1-S2 and 100 × （1-S2/S1）, was recommended for electrophysiological measurement in TRD patients.
