抑郁症患者纹状体多巴胺D2受体结合力与功能连接的相关性

Correlation between cerebral striatal dopamine D2 receptors non-displaceable binding potential and functional connectivity in patients with major depressive disorder

目的:应用11C-Raclopride PET/CT及rs-fMRI,探讨静息状态下首发抑郁症患者脑纹状体多巴胺D2受体结合力(non-displaceable binding potential,BPND)改变与功能连接(functional connectivity,FC)改变之间的关系,并分析其与临床症状是否具有相关性。方法:选择38例首发抑郁症患者(抑郁症组)及年龄、性别、受教育年数与其相匹配的健康志愿者40名(对照组)。所有受试者均在入组前进行汉密尔顿抑郁量表(24项版本)评分,入组后均在静息状态下接受脑11C-雷氯必利(11C-Raclopride)PET/CT和rs-fMRI检查。采用MIAKAT软件及DPARSF软件分别分析受试者脑纹状体多巴胺D2受体BPND及纹状体与全脑FC,应用SPSS 20.0软件及Rest 1.8软件进行配对样本t检验、两独立样本t检验探讨抑郁症患者脑纹状体多巴胺D2受体BPND及纹状体与全脑FC改变,并应用Pearson相关分析探讨两种改变之间的相关性及其与汉密尔顿抑郁量表评分的相关性。结果:与对照组相比,抑郁症组左右两侧纹状体(尾状核及壳核)D2受体BPND均减低(左侧尾状核:1.16±0.37,1.48±0.39;右侧尾状核:1.21±0.31,1.62±0.48;左侧壳核:1.73±0.47,2.21±0.66;右侧壳核:1.79±0.46,2.17±0.65;t=-3.66,-4.42,-3.68,-2.91,均P<0.001)。与对照组相比,抑郁症组左侧尾状核与左侧内侧前额叶(4.38±1.31,2.35±0.48)、左侧额中回(3.36±1.11,1.64±0.56)及左侧额上回(3.14±0.78,1.64±0.53)FC均增高(t=9.16,8.74,9.95,均P<0.05);抑郁症组左侧壳核与左侧内侧前额叶FC增高(4.10±1.42,2.42±0.64,t=6.82,P<0.05),左侧壳核与左侧前扣带回FC减低(1.60±0.55,2.68±0.84,t=-6.76,P<0.05);抑郁症组右侧尾状核与右侧内侧前额叶FC增高(4.32±1.30,2.33±0.63,t=8.51,P<0.05),右侧尾状核与右侧杏仁核FC减低(1.67±0.57,3.46±0.64,t=-8.27,P<0.05);抑郁症组右侧壳核与右侧内侧前额叶FC增高(3.77±1.25,2.31±0.63,t=6.49,P<0.05)。抑郁症组左侧尾状核BPND同左侧尾状核与左侧内侧前额叶FC值间为负相关(r=-0.66,P<0.001);抑郁症组左侧壳核BPND同左侧壳核与左侧内侧前额叶FC值间为负相关(r=-0.50,P=0.001);抑郁症组右侧尾状核BPND同右侧尾状核与右侧内侧前额叶FC值间为负相关(r=-0.67,P<0.001);抑郁症组右侧壳核BPND同右侧壳核与右侧内侧前额叶FC值间为负相关(r=-0.47,P=0.003)。抑郁症组左侧尾状核与左侧内侧前额叶FC同汉密尔顿抑郁量表总分、焦虑躯体化呈正相关(r=0.55,0.68,均P<0.001);抑郁症组左侧壳核与左侧内侧前额叶FC同认知障碍、迟缓呈正相关(r=0.37,0.40,P=0.021,0.01);抑郁症组右侧尾状核与右侧内侧前额叶FC同汉密尔顿抑郁量表总分、焦虑躯体化呈正相关(r=0.52,0.67,均P<0.001);抑郁症组右侧壳核与右侧内侧前额叶FC同认知障碍呈正相关(r=0.50,P=0.002)。结论:首发抑郁症患者纹状体区多巴胺D2受体结合力异常与其多巴胺奖赏环路相关脑区神经元活动协同性异常存在相关性,且与抑郁症临床症状相关,可能参与了抑郁症的发病机制。

Objective:To study the correlation between changes of cerebral striatal dopamine D 2 receptors non-displaceable binding potential(BPND),functional connectivity(FC)and clinical symptoms in patients with first-episode major depressive disorder(MDD),by 11C-Raclopride PET/CT and resting state fMRI(rs-fMRI).Methods:Thirty-eight first-episode depression patients(MDD group)and forty healthy volunteers(control group)matched with age,gender and years of education were selected.All subjects were scored with Hamilton depression scale(24 versions)before enrollment.All the subjects underwent cerebral 11C-Raclopride PET/CT and rs-fMRI in resting state.MIAKAT and DPARSF were used to analyze BPND of cerebral striatal dopamine D2 receptors and FC of striatum and the whole brain in subjects,respectively.Changes of striatal dopamine D2 receptors BPND and striatum and the whole brain FC of MDD were analyzed,and correlations among BPND,FC and Hamilton depression rating scale were calculated by Rest 1.8 and SPSS 20.0.Results:Compared with the control group,BPND of bilateral caudate nucleus and putamen dopamine D2 receptors in the MDD group were decreased(left caudate nucleus:1.16±0.37 vs 1.48±0.39,right caudate nucleus:1.21±0.31 vs 1.62±0.48,left putamen:1.73±0.47 vs 2.21±0.66,right putamen:1.79±0.46 vs 2.17±0.65,t=3.66,-4.42,-3.68,-2.91,all P<0.001).Besides,FC of left caudate nucleus and left medial prefrontal lobes(4.38±1.31,2.35±0.48),left caudate nucleus and left middle frontal gyrus(3.36±1.11,1.64±0.56),left caudate nucleus and left superior frontal gyrus(3.14±0.78,1.64±0.53),left putamen and left medial prefrontal lobes(4.10±1.42,2.42±0.64,t=6.82,P<0.05),right caudate nucleus and right medial prefrontal lobes(4.32±1.30,2.33±0.63,t=8.51,P<0.05),right putamen and right medial prefrontal lobes(3.77±1.25,2.31±0.63,t=6.49,P<0.05)in the MDD group were increased.FC of left putamen and left anterior cingulate(1.60±0.55,2.68±0.84,t=-6.76,P<0.05),right caudate nucleus and right amygdala(1.67±0.57,3.46±0.64,t=-8.27,P<0.05)in the MDD group were decreased.Furthermore,there were significant negative correlations between D2 receptors BPND of bilateral striatum and FC of the same lateral striatum and medial prefrontal lobes(r=-0.66,-0.50,-0.67,-0.47,all P<0.05).In MDD group,FC in left caudate nucleus and left medial prefrontal lobe were positively correlated with total score of Hamilton depression scale and anxiety somatization(r=0.55,0.68,P<0.001).FC in left putamen and left medial prefrontal cortex were positively correlated with cognitive impairment and retardation(r=0.37,0.40,P=0.021,0.001).FC of right caudate nucleus and right medial prefrontal lobe were positively correlated with Hamilton depression scale total score and anxiety somatization(r=0.52,0.67,all P<0.001).FC in right putamen and right medial prefrontal cortex was positively correlated with cognitive impairment(r=0.50,P=0.002).Conclusion:The abnormal BPND of cerebral striatal dopamine D2 receptor of patients with first-episode depression is related to the abnormal activity of dopamine reward circuit related neurons in patients with MDD,which was related to clinical symptoms of depression.It may be involved in the pathogenesis of depression.