双相障碍Ⅱ型抑郁发作患者脑功能网络连接与炎性细胞因子的相关性

The correlation between brain functional network connectivity and inflammatory cytokines in patients with bipolar disorder II depressive episodes

目的研究双相障碍Ⅱ型抑郁发作患者的默认网络和边缘系统功能连接、炎性细胞因子表达水平及二者的相关性。方法纳入33例双相障碍Ⅱ型抑郁发作患者和46名健康对照进行静息态磁共振扫描检查,图像预处理后采用独立成分分析方法从影像数据中提取默认网络和边缘系统,比较患者组和对照组的静息态脑网络间功能连接差异。检测患者组和对照组的血清炎性细胞因子白介素-6(interleukin,IL-6)、IL-8、IL-10、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和趋化因子C-C配体4(C-C motif chemokine ligand 4,CCL4)水平,探讨差异脑区的功能连接与炎性细胞因子表达水平之间的相关性。SPSS 17.0软件进行数据统计分析,两样本比较采用t检验或Mann-Whitney U检验,采用Spearman进行相关性检验。结果患者组默认网络的右侧内侧前额叶(团块体素大小=7体素,团块水平PGRF<0.05,MNI坐标:x=6,y=54,z=9,t=-3.765)、左侧额上回(团块体素大小=10体素,团块水平P_(GRF)<0.05,MNI坐标:x=-21,y=54,z=15,t=-4.139)功能连接减弱,边缘系统的左侧小脑Ⅳ、Ⅴ小叶(团块体素大小=21体素,团块水平P_(GRF)<0.05,MNI坐标:x=-15,y=-24,z=-30,t=4.468)和小脑后叶扁桃体(团块体素大小=8体素,团块水平P_(GRF)<0.05,MNI坐标:x=-15,y=-51,z=-45,t=4.138)功能连接增强。患者组血清炎性细胞因子IL-10[7.39(6.33,9.32)pg/mL,6.54(5.84,7.39)pg/mL,Z=-2.937,P=0.003]、CCL4[39.31(25.77,68.70)pg/mL,31.30(20.32,40.89)pg/mL,Z=-2.209,P=0.027]表达水平高于对照组。患者组小脑Ⅳ、Ⅴ小叶功能连接与血清IL-10水平呈正相关(r=0.432,P=0.031);小脑后叶扁桃体功能连接与血清IL-10水平呈正相关(r=0.429,P=0.032),与血清CCL4水平呈正相关(r=0.402,P=0.046)。结论静息态下双相障碍Ⅱ型抑郁发作患者默认网络和边缘系统功能连接异常,血清炎性细胞因子表达水平升高且可能与边缘系统功能连接存在相关。

Objective To investigate the functional connectivity of default mode network(DMN)and limbic system,the expression level of inflammatory cytokine and their correlation in bipolar disorder typeⅡ(BDⅡ)patients with depressive episodes.Methods Thirty-three BDⅡpatients with depressive episodes and forty-six healthy controls were recruited to complete the resting-state functional magnetic resonance imaging(rs-fMRI).After image preprocessing,the DMN and limbic system were extracted from the image data by independent component analysis(ICA),so as to compare the differences of functional connectivity of resting brain network between the patients and the controls.Serum levels of inflammatory cytokines interleukin-6(IL-6),interleukin-8(IL-8),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and C-C motif chemokine ligand 4(CCL4)in patients and healthy controls were detected.The correlation between functional connectivity of different brain regions and inflammatory cytokines was analyzed.SPSS 17.0 software was used for data statistical analysis.The two samples were compared using t-test or Mann-Whitney U-test,and Spearman was used for correlation testing.Result sIn BDⅡpatients,the functional connectivity of the right medial prefrontal cortex(cluster-size=7 voxel,cluster-level PGRF<0.05,MNI:x=6,y=54,z=9,t=-3.765)and the left superior frontal gyrus(cluster-size=10 voxel,cluster-level P_(GRF)<0.05,MNI:x=-21,y=54,z=15,t=-4.139)in DMN decreased,while the left cerebellumⅣandⅤlobules of limbic system(cluster-size=21 voxel,cluster-level P_(GRF)<0.05,MNI:x=-15,y=-24,z=-30,t=4.468)and cerebellar tonsil of left cerebellum posterior lobe(cluster-size=8 voxel,cluster-level P_(GRF)<0.05,MNI:x=-15,y=-51,z=-45,t=4.138)in the limbic system increased.Compared with the healthy controls,the serum levels of IL-10(7.39(6.33,9.32)pg/mL vs 6.54(5.84,7.39)pg/mL,Z=-2.937,P=0.003)and CCL4(39.31(25.77,68.70)pg/mL vs 31.30(20.32,40.89)pg/mL,Z=-2.209,P=0.027)were higher in BDⅡpatients.The functional connectivity of the left cerebellumⅣandⅤlobules was positively correlated with the serum levels of IL-10(r=0.432,P=0.031)and that of the cerebellar tonsil of left cerebellum posterior lobe was positively correlated with the serum levels of IL-10(r=0.429,P=0.032)and CCL4(r=0.402,P=0.046).Conclusion The functional connectivity of DMN and limbic system in BDⅡpatients with depressive episode is abnormal in resting-state fMRI.The expression level of inflammatory cytokines in patients'serum increases,and has correlation with the functional connection of limbic system.