童年期虐待对青少年抑郁症全脑灰质体积的影响——基于体素的形态学分析

Effect of childhood maltreatment on whole-brain gray matter volume in adolescents with major depressive disorder：a study of voxel-based morphometry

摘要

目的 探讨童年期虐待（childhood maltreatment，CM）是否会增加青少年罹患重性抑郁症（major depressive disorder，MDD）的风险以及脑灰质体积（gray matter volume，GMV）改变在CM和青少年MDD关系中发挥的调控作用，寻找青少年MDD可能的神经影像学指标用以辅助早期诊断。 方法 收集2021年10月至2022年7月于重庆医科大学附属第一医院就诊的12~17岁青少年MDD患者47例（MDD组）和年龄、性别、受教育年限与之相匹配的健康对照28例（对照组）并进行3DT1加权结构像磁共振成像扫描，使用基于体素的形态学测量（voxel‑based morphometry，VBM）方法比较2组GMV的差异，组间比较采用独立样本t检验。采用spearman相关性分析来分析差异脑区GMV以及17项汉密尔顿抑郁量表（Hamilton Depression Scale，HAMD-17）评分与儿童期创伤量表（Childhood Trauma Questionnaire Short Form，CTQ-SF）评分的相关性。建立中介效应模型探索差异脑区GMV在CM和抑郁之间关系的调控作用，采用Bootstrap方法进行检验。通过使用受试者工作曲线（receiver operating characteristic curve，ROC）来分析有统计学差异脑区的灰质体积大小在MDD诊断中的价值。 结果 MDD组CTQ-SF总分和分维度评分显著高于对照组（P<0.05）。与对照组相比，MDD组左侧距状裂周围皮层（t=-5.61），右侧颞中回（t=-4.95），左侧背外侧额上回（t=-4.59），右侧中央旁小叶（t=-4.27）的GMV减少（P<0.05，基于体素的FDR校正，体素阈值为1 000），左侧距状裂周围皮层GMV减少对MDD诊断有一定准确性，曲线下面积为0.843，约登指数为0.587。差异脑区GMV与CTQ-SF总分，情感虐待（emotional abuse，EA）评分，躯体忽视（physical neglect，PN）评分或情感忽视（emotional neglect，EN）呈负相关（P<0.05），其中，PN与左侧距状裂周围皮层的相关性通过Bonferroni多重比较校正，P<0.002；CTQ-SF总分（r_s =0.611，P=0.000）。EA得分（r_s =0.617，P=0.000），EN得分（r_s =0.604，P=0.000）和PN得分（r_s =0.523，P=0.000）均与HAMD-17评分呈现显著正相关，均通过Bonferroni多重比较校正，P<0.008。中介分析发现左侧距状裂周围皮层，右侧颞中回，左侧背外侧额上，右侧中央旁小叶GMV显示了对CM和抑郁之间关系的间接效应；左侧距状裂周围皮层GMV显示了EN和抑郁之间关系的间接效应；左侧距状裂周围皮层，右侧颞中回GMV显示了PN和抑郁之间关系的间接效应。 结论 青少年MDD人群相较于健康人群遭受各个维度CM的情况更严重。左侧距状裂周围皮层、右侧颞中回、左侧背外侧额上回和右侧中央旁小叶GMV的减少在CM经历和青少年抑郁之间发挥了至关重要的调控作用，不同的CM类型可以通过不同脑区GMV改变影响抑郁的发病风险。

Abstract

Objective To investigate whether childhood maltreatment（CM） can increase the risk of major depressive disorder（MDD） in adolescents and the regulatory role of gray matter volume（GMV） change in the association between CM and MDD in adolescents，and to identify possible neuroimaging indicators for MDD in adolescents to assist in early diagnosis. Methods A total of 47 adolescents with MDD，aged 12-17 years，who attended The First Affiliated Hospital of Chongqing Medical University from October 2021 to July 2022 were enrolled as MDD group，and 28 healthy controls，matched for age，sex，and years of education，were enrolled as control group. All subjects underwent three-dimensional T1-weighted magnetic resonance imaging（MRI） scans，and the voxel-based morphometry（VBM） methods were used to compare GMV between the two groups. The independent samples t-test was used for comparison between the two groups. The Spearman correlation analysis was used to investigate the correlation of GMV of different brain regions and 17-item Hamilton Depression Rating Scale（HAMD-17） score with Childhood Trauma Questionnaire-Short Form（CTQ-SF） score. A mediating effect model was established to investigate the regulating effect of GMV of different brain regions in the association between CM and depression，and the Bootstrap method was used for testing. The receiver operating characteristic（ROC） curve was used to investigate the value of GMV of different brain regions in the diagnosis of MDD. Results Compared with the control group，the MDD group had significantly higher total score of CTQ-SF and scores of each dimension（P<0.05）. Compared with the control group，the MDD group had significant reductions in the GMV of the left calcarine cortex （t=-5.61），the right middle temporal gyrus（t=-4.95），the left dorsolateral superior frontal gyrus（t=-4.59），and the right paracentral lobe（t=-4.27），with a P value of <0.05 based on voxel-based FDR correction and a voxel threshold of 1000. The reduction in the GMV of the left calcarine cortex had a certain accuracy in the diagnosis of MDD，with an area under the ROC curve of 0.843 and a Yoden index of 0.587. The GMV of the above four brain regions was negatively correlated with the total score of CTQ-SF，emotional abuse（EA） score，physical neglect（PN） score，and emotional neglect（EN） score（P<0.05），and the correlation between PN score and GMV of the left calcarine cortex was corrected by Bonferroni multiple comparisons（P<0.002）. The total score of CTQ-SF（r_s =0.611，P=0.000），EA score（r_s =0.617，P=0.000），EN score（r_s =0.604，P=0.000），and PN score（r_s =0.523，P=0.000） were significantly positively correlated with HAMD-17 score，which were all corrected by Bonferroni multiple comparisons（P<0.008）. The mediation analysis showed that GMV of the left calcarine cortex，the right middle temporal gyrus，the left dorsolateral superior frontal gyrus，and the right paracentral lobe showed an indirect effect on the association between CM and depression；GMV of the left calcarine cortex showed an indirect effect on the association between EN and depression；GMV of the left calcarine cortex and the right middle temporal gyrus showed an indirect effect on the association between PN and depression. Conclusion Adolescents with MDD suffer more from all dimensions of CM than healthy individuals. Reductions in GMV of the left calcarine cortex，the right middle temporal gyrus，the left dorsolateral superior frontal gyrus，and the right paracentral lobe play a crucial regulatory role in the association between CM experience and depression in adolescents，and different types of CM can affect the risk of depression through changes in GMV of different brain regions.

关键词

青少年抑郁症 / 磁共振成像 / 灰质体积 / 童年期虐待

Key words

adolescent depression / magnetic resonance imaging / gray matter volume / childhood maltreatment

基金资助

国家自然科学基金资助项目(81971286)

重庆市科技创新与应用发展专项重点资助项目(CSTC2021-jscx-gksb-N0002)