皮质下灰质体积与氯胺酮抗抑郁作用的关系

Subcortical volumes and ketamine’s antidepressant efficacy in major depressive disorder

目的探讨氯胺酮治疗前皮质下灰质体积与氯胺酮抗抑郁作用的关系。方法纳入难治性或伴自杀意念的抑郁症患者45例,进行2周共6次氯胺酮静脉注射(0.5 mg/kg,3次/周)。采用蒙哥马利抑郁量表(Montgomery-Åsberg Depression Rating Scale,MADRS)及贝克自杀意念量表第一部分(Beck Scale for Suicide Ideation-part one,SSI-Ⅰ)评估抑郁症状及自杀意念。患者治疗前进行3.0T MRI扫描,采集得到的3DT1数据采用Freesurfer软件进行自动化处理,计算皮质下灰质结构(海马、杏仁核、丘脑、尾状核、壳核、苍白球)体积,并与45名健康对照者(对照组)皮质下灰质体积进行比较。采用线性回归分析治疗前皮质下灰质体积与氯胺酮治疗后MADRS分数改变值及SSI-Ⅰ改变值的关系(改变值=治疗前分数-治疗后分数)。结果与对照组相比,抑郁症组双侧海马体积减小[左侧:(2993±276)mm3比(2785±263)mm3,F=12.928,P=0.001;右侧:(3117±254)mm3比(2949±270)mm3,F=8.217,P=0.005]。难治性患者治疗前右侧丘脑体积与6次氯胺酮治疗后MADRS分数改变值呈正相关(B=0.009,t=3.434,P=0.002)。结论难治性抑郁症患者治疗前右侧丘脑体积越大,氯胺酮抗抑郁效果越好;治疗前丘脑体积可能是氯胺酮抗抑郁作用的预测指标。

Objective To examine the relationship between subcortical volumes and ketamine’s antidepressant effects.Methods Forty-five depressive patients with treatment resistance or suicide ideation were involved and received six infusions of ketamine for two weeks(0.5 mg/kg,thrice-weekly).Depressive symptoms were assessed by Montgomery-Åsberg Depression Rating Scale(MADRS)and suicide ideation was assessed by Beck Scale for Suicide Ideation-part one(SSI-Ⅰ).Subcortical volumes underwent 3.0T-weighted MRI.The Freesurfer software was used to process the T1 images,which used a set of automated sequences to analyze subcortical volumes.Forty-five healthy controls were collected and their subcortical volumes were compared with the patients’volumes.Linear regression analysis was used to determine the association between pre-treatment subcortical volumes and change in MADRS score as well as SSI scores after ketamine treatment(change=pre-treatment scores minus post-treatment scores).Results In comparison to the healthy controls,depressive patients had decreased bilateral hippocampal volumes(Left:(2993±276)mm3vs.(2785±263)mm3,F=12.928,P=0.001;Right:(3117±254)mm3vs.(2949±270)mm3,F=8.217,P=0.005).Pre-treatment volumes of right thalamus were positively correlated with change in MADRS scores after six infusions in patients with treatment resistance(B=0.009,t=3.434,P=0.002).Conclusion Six ketamine infusions exerted enhanced antidepressant effects in treatment-resistant depression patients with relatively larger thalamus.Volume of thalamus could be used as a biomarker of six ketamine’s antidepressants treatment outcome.