加味酸枣仁汤与艾司唑仑对慢性失眠障碍患者默认网络有效连接的趋同性调节

Convergent modulation of default mode network effective connectivity by modified Suanzaoren Decoction and estazolam in patients with chronic insomnia disorder

中文关键词:  加味酸枣仁汤  艾司唑仑  慢性失眠障碍  默认网络  有效连接  格兰杰因果分析

英文关键词:Modified Suanzaoren Decoction  Estazolam  Chronic insomnia disorder  Default mode network  Effective connectivity  Granger causality analysis

中文摘要:

      背景 加味酸枣仁汤与艾司唑仑均为临床治疗慢性失眠障碍（CID）的有效手段。默认网络（DMN）功能紊乱被认为是CID的关键病理生理机制之一，然而，加味酸枣仁汤和艾司唑仑是否通过相似的神经机制调节DMN功能，目前尚不清楚。目的 探讨加味酸枣仁汤与艾司唑仑对阴虚火旺型CID患者DMN核心节点与全脑及自身双向有效连接（EC）重塑特征的一致性，为揭示两种药物治疗CID的共同神经机制提供影像学证据。方法 连续纳入2020年10月—2023年9月于内蒙古自治区精神卫生中心门诊就诊的、符合《国际睡眠障碍分类（第3版）》（ICSD-3）诊断标准的CID患者82例，依据患者治疗意愿，分为加味酸枣仁汤组（n=52）和艾司唑仑组（n=30），均干预6周，最终完成随访者66例，其中加味酸枣仁汤组41例、艾司唑仑组25例。CID患者在治疗前后均行静息态功能磁共振成像扫描，选取DMN核心节点内侧前额叶皮层（mPFC）、双侧顶下小叶（IPL）及楔前叶（PCUN）作为种子点。采用格兰杰因果分析（GCA）探究各种子点与DMN内其他节点及全脑其他脑区的双向EC。于治疗前后检测肝肾功能指标以评价用药安全性。结果 基线期，加味酸枣仁汤组左侧IPL至左侧额中回（眶部）/直回的EC高于艾司唑仑组，差异有统计学意义（t=5.24，Z=4.84，体素水平P<0.001，集群水平P<0.05，GRF校正）；两组其余DMN核心节点与全脑各脑区EC比较，差异均无统计学意义（P均>0.05）。组内治疗前后比较显示：两组左侧IPL至辅助运动区（SMA）的EC（加味酸枣仁汤组：t=-6.28，Z=5.208；艾司唑仑组：t=-5.58，Z=4.425）、PCUN至左侧IPL的EC均较治疗前减弱（加味酸枣仁汤组：t=-5.85，Z=4.943；艾司唑仑组：t=-5.75，Z=4.515）；SMA至左侧IPL的EC（加味酸枣仁汤组：t=5.89，Z=4.968；艾司唑仑组：t=6.15，Z=4.720）、左侧IPL至PCUN的EC均较治疗前增强（加味酸枣仁汤组：t=5.29，Z=4.579；艾司唑仑组：t=4.55，Z=3.826）（体素水平P均<0.001，集群水平P<0.05，GRF校正）。两组组内治疗前后肝肾功能指标比较，差异均无统计学意义（P均>0.05）。结论 加味酸枣仁汤与艾司唑仑治疗后，阴虚火旺型CID患者DMN左侧IPL与SMA、PCUN之间的EC均呈现方向一致的重塑。

英文摘要:

      Background Both modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder （CID）. Default mode network （DMN） dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However， it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity.Objective To investigate the convergent remodeling characteristics of bidirectional effective connectivity （EC） of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam， so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID.Methods Eighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder， third edition （ICSD-3） were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference， patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group （n=52） or the estazolam group （n=30）. Ultimately， 66 patients completed follow-up assessments （modified Suanzaoren Decoction group， n=41； estazolam group， n=25）. All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex （mPFC）， bilateral inferior parietal lobule （IPL）， and precuneus （PCUN） were selected as seed regions. Granger causality analysis （GCA） was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments.Results At baseline， significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus （t=5.24， Z=4.84， voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）， with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions （P>0.05）. Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically， EC from the left IPL to the supplementary motor area （SMA） decreased after treatment （modified Suanzaoren Decoction group： t=-6.28， Z=5.208； estazolam group： t=-5.58， Z=4.425）. Conversely， EC from the SMA to the left IPL increased （modified Suanzaoren Decoction group： t=5.89， Z=4.968； estazolam group： t=6.15， Z=4.720）. Furthermore， both groups demonstrated reduced EC from the PCUN to the left IPL （modified Suanzaoren Decoction group： t=-5.85， Z=4.94； estazolam group： t=-5.75， Z=4.515）， and elevated EC from the left IPL to the PCUN （modified Suanzaoren Decoction group： t=5.29， Z=4.579； estazolam group： t=4.55， Z=3.826） （voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）. No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group （P>0.05）.Conclusion In CID patients with Yin-deficiency and fire-hyperactivity syndrome， both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. ［Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region （number， 2019MS08099）； ClinicalTrials.gov number， NCT06452953］