Objectives: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment.
Methods: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki).
Results: Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment.
Conclusions: There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
目的: 伴快感缺失的抑郁症(major depressive disorder，MDD)患者预后较差。然而，MDD的病因和影像学基础尚不明确。目前，针对MDD的脑影像学研究并未深入探讨相关网络节点属性与MDD快感缺失的关系。因此，本研究旨在探讨重度快感缺失抑郁症(MDD patients with severe anhedonia，MDD-SA)患者与轻度快感缺失抑郁症(MDD patients with mild anhedonia，MDD-MA)患者在抗抑郁药物治疗前后脑功能节点特征的差异。方法: 招募90例MDD急性发作期的患者。采用24项汉密尔顿抑郁量表(24-Item Hamilton Depression Scale，HAMD-24)和斯奈斯-汉密尔顿快感量表(Snaith-Hamilton Pleasure Scale，SHAPS)于基线期和治疗第6个月末时分别评估MDD患者抑郁和快感缺失的严重程度。将SHAPS评分最高的25%的MDD患者纳入MDD-SA组(n=19)，将评分最低的25%的MDD患者纳入MDD-MA组(n=18)。MDD患者均接受抗抑郁药物治疗，并于基线期和治疗第6个月末时采集其脑功能影像数据。应用图论(graph theory)的方法分析MDD-SA和MDD-MA患者脑功能节点属性的差异，分析的指标包括节点效率(efficiency，ei)和度(degree，ki)。结果: 重复测量双因素协方差分析(repeated measures 2-factor ANCOVA)显示，MDD患者左侧额上回(left superior frontal gyrus，LSFG)的ei值(P=0.003)和ki值(P=0.008)以及左侧内侧眶额回(left medial orbital-frontal gyrus，LMOFG)的ei值(P=0.004)和ki值(P=0.008)具有显著的组间(快感缺失)主效应。与MDD-MA组相比，MDD-SA组基线时LSFG的ei值(P=0.015)和ki值(P=0.021)显著性增高，LMOFG的ei值(P=0.015)和ki值 (P=0.037)显著性增高。基线时，SHAPS评分越高，LSFG的ei值(P=0.019)和ki值(P=0.026)越高，LMOFG的ei值也越高(P=0.040)；治疗第6个月末时，SHAPS评分越高，LSFG的ei值越高(P=0.049)。多元线性回归结果显示性别与基线期LSFG的ei值和ki值有关(r=-0.014，P=0.004；r=-1.153，P=0.001)，发病年龄与治疗第6个月末时LSFG的ki值(r= -0.420，P=0.034)有关。基线时的SHAPS评分与治疗第6个月末时的HAMD-24评分呈正相关(r=0.387，P=0.022)。结论: MDD-SA和MDD-MA患者在脑功能节点属性上存在显著差异，其中存在显著差异脑区的节点属性(如LSFG较高的ei值)与快感缺失的严重程度呈正相关。这些有差异的节点属性有望成为MDD患者预后的生物学指标。MDD-SA患者LSFG较高的ei和ki值说明MDD-SA患者的LSFG与网络中其他节点的连接增强，这种增强可能是一种代偿性机制或者保护性机制。这种机制可能是MDD快感缺失的病理学机制的重要组成部分。此外，MDD-SA患者的预后较差，提示较重的快感缺失可能预测MDD患者较差的预后。性别和发病年龄对LSFG的基线期以及治疗第6个月末时的节点属性值均有影响。.
目的: 伴快感缺失的抑郁症(major depressive disorder，MDD)患者预后较差。然而，MDD的病因和影像学基础尚不明确。目前，针对MDD的脑影像学研究并未深入探讨相关网络节点属性与MDD快感缺失的关系。因此，本研究旨在探讨重度快感缺失抑郁症(MDD patients with severe anhedonia，MDD-SA)患者与轻度快感缺失抑郁症(MDD patients with mild anhedonia，MDD-MA)患者在抗抑郁药物治疗前后脑功能节点特征的差异。
方法: 招募90例MDD急性发作期的患者。采用24项汉密尔顿抑郁量表(24-Item Hamilton Depression Scale，HAMD-24)和斯奈斯-汉密尔顿快感量表(Snaith-Hamilton Pleasure Scale，SHAPS)于基线期和治疗第6个月末时分别评估MDD患者抑郁和快感缺失的严重程度。将SHAPS评分最高的25%的MDD患者纳入MDD-SA组(n=19)，将评分最低的25%的MDD患者纳入MDD-MA组(n=18)。MDD患者均接受抗抑郁药物治疗，并于基线期和治疗第6个月末时采集其脑功能影像数据。应用图论(graph theory)的方法分析MDD-SA和MDD-MA患者脑功能节点属性的差异，分析的指标包括节点效率(efficiency，ei)和度(degree，ki)。
结果: 重复测量双因素协方差分析(repeated measures 2-factor ANCOVA)显示，MDD患者左侧额上回(left superior frontal gyrus，LSFG)的ei值(P=0.003)和ki值(P=0.008)以及左侧内侧眶额回(left medial orbital-frontal gyrus，LMOFG)的ei值(P=0.004)和ki值(P=0.008)具有显著的组间(快感缺失)主效应。与MDD-MA组相比，MDD-SA组基线时LSFG的ei值(P=0.015)和ki值(P=0.021)显著性增高，LMOFG的ei值(P=0.015)和ki值 (P=0.037)显著性增高。基线时，SHAPS评分越高，LSFG的ei值(P=0.019)和ki值(P=0.026)越高，LMOFG的ei值也越高(P=0.040)；治疗第6个月末时，SHAPS评分越高，LSFG的ei值越高(P=0.049)。多元线性回归结果显示性别与基线期LSFG的ei值和ki值有关(r=-0.014，P=0.004；r=-1.153，P=0.001)，发病年龄与治疗第6个月末时LSFG的ki值(r= -0.420，P=0.034)有关。基线时的SHAPS评分与治疗第6个月末时的HAMD-24评分呈正相关(r=0.387，P=0.022)。
结论: MDD-SA和MDD-MA患者在脑功能节点属性上存在显著差异，其中存在显著差异脑区的节点属性(如LSFG较高的ei值)与快感缺失的严重程度呈正相关。这些有差异的节点属性有望成为MDD患者预后的生物学指标。MDD-SA患者LSFG较高的ei和ki值说明MDD-SA患者的LSFG与网络中其他节点的连接增强，这种增强可能是一种代偿性机制或者保护性机制。这种机制可能是MDD快感缺失的病理学机制的重要组成部分。此外，MDD-SA患者的预后较差，提示较重的快感缺失可能预测MDD患者较差的预后。性别和发病年龄对LSFG的基线期以及治疗第6个月末时的节点属性值均有影响。
Keywords: anhedonia; functional magnetic resonance imaging; major depressive disorder; nodal network.