心境稳定剂单药或联合治疗对双相躁狂患者外周血单核细胞糖原合成酶激酶3活性的影响

摘要

Objective To explore the therapeutic effects of of different mood stabilizers single or combined atypical antipsychotics on glycogen synthase kinase 3 (GSK3) activity in the peripheral blood mononuclear cells (PBMCs) of patients with bipolar mania. Methods Thirty-six patients with bipolar I mania were enrolled for treatment with mood stabilizers single or combined atypical antipsychotics for eight weeks. Twenty mL of blood was collected from each patient by venipuncture at week 0, week 4 and week 8. The level of pSer21-GSK3α;pSer9-GSK3β, total GSK3α and GSK3β in PBMCs of patients were measured by Western blotting. Clinical symptoms were assessed with the Young mania ratings scale ( YMRS) and other clinical rating scales at the same time. Results The average scores of YMRS, and CGI-S significantly reduced at week 8 compared with those at week 0 (P<0. 001); meanwhile, the level of pSer21-GSK3α and pSer9-GSK3β increased at week 8; Compared with valproate group, the relative ratio of pSer-GSK3β/total-GSK3β was higher than that of lithium group ( P=0. 020 ) . There was a positive correlation between ratio of pSer9-GSK3β to toal-GSK3β at baseline and the average score of YMRS reduction from baseline to week 0 (P=0. 043). Excluding patients with manic episodes more than 3 times, there was a significant trend of increase (P=0. 020). The correlation was significant in lithium group. However, it did not appear in valproate group. Conclusion Mood stabilizers single or combined atypical antipsychotics could decrease glycogen synthase kinase 3 ( GSK3 ) activity in the peripheral blood mononuclear cells ( PBMCs) of patients with bipolar mania. Compared with valproate treatment, lithium single or combined treatment could significantly reduce the activity of GSK3 of patients with bipolar mania.%目的：探讨不同心境稳定剂单药或联合非典型抗精神病药物治疗对双相躁狂患者外周血单核细胞( peripheral blood mononuclear cells, PBMCs)糖原合成酶激酶3(glycogen synthase kinase 3, GSK3)活性的影响。方法纳入双相I型躁狂发作患者36例,给予碳酸锂或丙戊酸钠联合非典型抗精神病药物8周。分别于基线、4周和8周末采集患者外周静脉血20 mL,应用免疫印迹法检测患者PBMCs的GSK3α和GSK3β丝氨酸磷酸化水平( pSer-GSK3α, pSer-GSK3β)以及总GSK3水平( total-GSK3α和total-GSK3β)。采用杨氏躁狂量表( Young Mania Ratings Scale,YMRS)和临床症状严重度量表( Clinical Global Impression-Scale, CGI-S)等评估症状变化。结果治疗8周,各组患者的YMRS、CGI-S等评分均明显降低(P<0．001),与此同时,治疗后PBMCs的pSer-GSK3α、pSer-GSK3β较治疗前明显升高；不同心境稳定剂组间比较,pSer-GSK3β/total-GSK3β相对比值差异存在统计学意义(P=0．020),锂盐组变化明显(P=0．024)；相关分析显示,pSer9-GSK3β/total-GSK3β比值与4周末YMRS减分绝对值呈负相关(r=-0.413,P=0．043)。剔除反复躁狂发作(≥3次)患者,这一趋势更加显著(r=-0.543,P=0．020)。其中锂盐组呈现了相似的变化(r=-0.432,P=0．083),而丙戊酸钠组无。结论心境稳定剂单药或联合非典型抗精神病药物治疗可降低双相躁狂患者PBMCs的GSK3活性,碳酸锂单药或联合治疗相比丙戊酸钠,可以更显著降低双相躁狂患者的GSK3活性。