基于弥散张量成像对精神分裂症药物治疗不同反应者的研究

曾嘉欣; 张文静; 付桂; 肖媛; 唐碧秋; 姚骊; 吕粟

doi:10.7507/1001-5515.201905062

基于弥散张量成像对精神分裂症药物治疗不同反应者的研究

doi: 10.7507/1001-5515.201905062

详细信息

通讯作者:
吕粟，Email：lusuwcums@tom.com

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出版历程
- 收稿日期: 2019-05-22
- 修回日期: 2020-02-18
- 发布日期: 2020-03-17

A preliminary study on schizophrenia of distinct antipsychotic response based on diffusion tensor imaging

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Corresponding author: LU Su, Email: lusuwcums@tom.com

摘要

摘要: 本文旨在探索首发未用药状态下，抗精神病药物治疗不同反应的精神分裂症患者白质参数是否存在不同模式的改变。采集 60 例首发未用药精神分裂症患者（药物治疗有效者 39 例，难治者 21 例）与 69 例年龄、性别匹配的健康对照的磁共振弥散张量成像（DTI）数据，运用 FSL 软件进行数据处理，提取反映白质微结构完整性的参数并进行确定性的纤维追踪，并基于纤维追踪的结果构建网络矩阵，通过方差分析比较三组间白质参数及白质连接网络拓扑属性的差异。结果发现相比于健康对照，药物治疗有效组白质异常主要表现在丘脑前辐射、胼胝体压部、扣带束和上纵束，而药物难治组白质异常主要分布在丘脑前辐射、扣带束、穹隆和脑桥交叉纤维束。药物难治组在丘脑前辐射表现出比药物治疗有效组更严重的白质异常。此外，三组被试之间白质连接网络拓扑属性差异无统计学意义。支持向量机（SVM）的结果显示两个患者亚组之间分类的准确度为 63.37%（P = 0.04）。该研究表明精神分裂症抗精神病药物治疗不同反应者存在不同模式的白质微结构完整性损伤，这对基线未用药状态下区分和治疗不同反应患者、改善患者预后具有指导作用。
- 精神分裂症 /
- 弥散张量成像 /
- 基于纤维束的空间统计分析 /
- 治疗结果
Abstract: The study aims to investigate whether there is difference in pre-treatment white matter parameters in treatment-resistant and treatment-responsive schizophrenia. Diffusion tensor imaging (DTI) was acquired from 60 first-episode drug-naïve schizophrenia (39 treatment-responsive and 21 treatment-resistant schizophrenia patients) and 69 age- and gender-matched healthy controls. Imaging data was preprocessed via FSL software, then diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted. Besides, structural network matrix was constructed based on deterministic fiber tracking. The differences of diffusion parameters and topology attributes between three groups were analyzed using analysis of variance (ANOVA). Compared with healthy controls, treatment-responsive schizophrenia showed altered white matter mainly in anterior thalamus radiation, splenium of corpus callosum, cingulum bundle as well as superior longitudinal fasciculus. While treatment-resistant schizophrenia patients showed white matter abnormalities in anterior thalamus radiation, cingulum bundle, fornix and pontine crossing tract relative to healthy controls. Treatment-resistant schizophrenia showed more severe white matter abnormalities in anterior thalamus radiation compared with treatment-responsive patients. There was no significant difference in white matter network topological attributes among the three groups. The performance of support vector machine (SVM) showed accuracy of 63.37% in separating the two patient subgroups (P = 0.04). In this study, we showed different patterns of white matter alterations in treatment-responsive and treatment-resistant schizophrenia compared with healthy controls before treatment, which may help guiding patient identification, targeted treatment and prognosis improvement at baseline drug-naïve state.
- schizophrenia /
- diffusion tensor imaging /
- tract-based spatial statistics /
- treatment outcome

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图 1 三组受试者组间白质参数的差异　

a. 药物治疗有效组患者相对于健康对照组降低的 FA；b. 药物难治组患者相对于健康对照降低的 FA；c. 药物治疗有效组患者相对于药物难治组患者增加的 FA；d. 药物治疗有效组相对于健康对照组增高的 RD。红-黄色标记为 FA（图 a，b，c），蓝-绿标记为 RD（图 d），彩色条显示组间差异的相应纤维体素经过 FWE 校正以后的 1－P 值

Figure 1. White matter parameter differences between the three groups

a. reduced FA in treatment-responsive patients relative to healthy controls; b. reduced FA in treatment-resistant patients relative to healthy controls; c. increased FA in treatment-responsive patients relative to treatment-resistant patients; d. increased RD in treatment-responsive patients relative to healthy controls. Red-yellow labels indicate FA (Fig a, b and c), blue-green labels indicate RD (Fig d), and color-bar indicates 1-P value after FWE correction of fiber voxels between group comparison

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图 2 精神分裂症患者白质异常与临床表现的相关性

Figure 2. Correlation between white matter abnormalities and clinical assessment in schizophrenia

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表 1 人口学及临床资料

Table 1. Demographical and clinical information

项目	治疗有效者（ $ \bar x$ ± s，n = 39）	药物难治者（ $ \bar x$ ± s，n = 21）	健康对照（ $ \bar x$ ± s，n = 69）	F（t）或 χ² 值	P 值
年龄/岁	24.21 ± 7.67	24.33 ± 9.36	24.52 ± 8.37	0.02	0.98^a
性别（男/女）	14/25	11/10	29/40	1.53	0.47^b
教育年限/年	13.08 ± 2.69	11.76 ± 2.72	12.98 ± 2.17	2.41	0.09^a
基线 GAF	29.77 ± 10.34	26.00 ± 7.18	—	1.49	0.14^c
基线 PANSS 总分	98.82 ± 16.63	99.29 ± 17.34	—	−0.10	0.92^c
基线 PANSS 阳性症状评分	25.79 ± 6.63	23.38 ± 6.14	—	1.41	0.17^c
基线 PANSS 阴性症状评分	17.64 ± 7.02	20.38 ± 7.55	—	−1.37	0.18^c
基线 PANSS 一般症状评分	47.38 ± 7.55	48.14 ± 9.57	—	−0.31	0.76^c
随访 PANSS 总分	42.42 ± 9.43	70.21 ± 18.73	—	−7.61	<0.01^c
随访 PANSS 阳性症状评分	8.41 ± 2.78	15.89 ± 7.01	—	−5.83	<0.01^c
随访 PANSS 阴性症状评分	11.41 ± 4.24	16.84 ± 5.08	—	−4.29	<0.01^c
随访 PANSS 一般症状评分	22.23 ± 4.99	36.74 ± 10.79	—	−7.04	<0.01^c
a：方差分析 P 值；b：χ² 检验 P 值；c：双样本 t 检验 P 值

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表 2 不同被试组网络和节点拓扑属性曲线下面积（ $\overline {{x}} \;{b\text{±}}\; {{s}}$ ）比较

Table 2. Area under curve ( $\overline {{x}} \;{b\text{±}}\; {{s}}$ ) comparisons of network and nodal topological properties between groups

指标	治疗有效者	药物难治者	正常对照	F 值	P 值
σ	0.079 ± 0.009	0.079 ± 0.009	0.079 ± 0.011	0.014	0.986
γ	0.083 ± 0.010	0.083 ± 0.010	0.083 ± 0.012	0.012	0.988
λ	0.042 ± 0.000	0.042 ± 0.000	0.042 ± 0.001	0.118	0.888
Cp	0.157 ± 0.001	0.156 ± 0.001	0.155 ± 0.002	0.288	0.750
Lp	0.814 ± 0.001	0.820 ± 0.001	0.816 ± 0.001	2.150	0.121
节点效率	0.020 ± 0.000	0.020 ± 0.000	0.020 ± 0.000	2.215	0.113
节点介数	2.275 ± 0.073	2.252 ± 0.086	2.255 ± 0.095	0.800	0.451
节点度	0.463 ± 0.000	0.463 ± 0.000	0.463 ± 0.000	0.413	0.663

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