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:

      【【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，两者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治疗阴虚火旺型CID患者后，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，为揭示两种疗法治疗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52例（配方颗粒2次/日，早、晚餐后30分钟温水服用），艾司唑仑组30例（1 mg/晚，每晚睡前30分钟口服），均干预6周，最终完成随访者66例（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，双侧顶下小叶，楔前叶作为种子点，采用格兰杰因果分析（GCA）探究上述种子点与DMN内其他节点及全脑其他脑区的双向EC，并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，加味酸枣仁汤组左顶下小叶至左侧额中回（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矫正）；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：两组左顶下小叶至辅助运动区的EC（加味酸枣仁汤组：t=-6.28，Z=5.21；艾司唑仑组：t=-5.58，Z=4.42）、楔前叶至左顶下小叶的EC均较治疗前减弱（加味酸枣仁汤组：t=-5.85，Z=4.94；艾司唑仑组:t=-5.75，Z=4.52）；辅助运动区至左顶下小叶的EC（加味酸枣仁汤组：t=5.89，Z=4.97；艾司唑仑组：t=6.15，Z=4.72）、左顶下小叶至楔前叶的EC均较治疗前增强（加味酸枣仁汤组：t=5.29，Z=4.58；艾司唑仑组：t=4.55，Z=3.83）（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阴虚火旺型CID患者后，两组患者DMN左侧顶下小叶与辅助运动区、楔前叶之间的EC均呈现方向一致的重塑。

英文摘要:

      【Abstract】 Background Modified Suanzaoren Decoction and estazolam are both effective treatments for chronic insomnia disorder (CID). Default mode network (DMN) dysfunction is considered one of the key pathophysiological mechanisms underlying CID. However, whether these two treatments modulate DMN function through similar neural mechanisms remains unclear. Objective To investigate the convergent patterns of bidirectional effective connectivity (EC) remodeling between DMN core nodes and the whole brain following modified Suanzaoren Decoction versus estazolam treatment in CID patients with Yin-deficiency and fire-excess syndrome, and to provide imaging evidence for a shared neural mechanism of the two therapies in treating CID. Methods Eighty-two CID patients diagnosed according to the International Classification of Sleep Disorders, third edition (ICSD-3) were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center between October 2020 and September 2023. Based on treatment preference, patients were assigned to the modified Suanzaoren Decoction group (n=52; formula granules twice daily, taken with warm water 30 minutes after breakfast and dinner) or the estazolam group (n=30; 1 mg/night, taken orally 30 minutes before bedtime) for a 6-week intervention. Sixty-six patients completed follow-up (modified Suanzaoren Decoction group, n=41; estazolam group, n=25). All CID patients underwent resting-state functional magnetic resonance imaging before and after treatment. The DMN core nodes—medial prefrontal cortex, bilateral inferior parietal lobules, and precuneus—were selected as seed regions. Granger causality analysis was employed to investigate bidirectional EC between the seed regions and other nodes within the DMN as well as other brain regions across the whole brain. Liver and renal function indices were assessed before and after treatment to evaluate medication safety. Results At baseline, a significant between-group difference was observed in EC from the left inferior parietal lobule to the left middle frontal gyrus (orbital part)/gyrus rectus (t=5.24, Z=4.84; voxel-level P<0.001, cluster-level P<0.05, GRF-corrected), with higher EC in the modified Suanzaoren Decoction group than in the estazolam group. No significant between-group differences were found for EC between other DMN core nodes and whole-brain regions (P>0.05). Within-group pre- versus post-treatment comparisons revealed that in both groups, EC from the left inferior parietal lobule to the supplementary motor area decreased after treatment (modified Suanzaoren Decoction group: t=?6.28, Z=5.21; estazolam group: t=?5.58, Z=4.42), while EC from the supplementary motor area to the left inferior parietal lobule increased (modified Suanzaoren Decoction group: t=5.89, Z=4.97; estazolam group: t=6.15, Z=4.72). Furthermore, EC from the precuneus to the left inferior parietal lobule decreased (modified Suanzaoren Decoction group: t=?5.85, Z=4.94; estazolam group: t=?5.75, Z=4.52), and EC from the left inferior parietal lobule to the precuneus increased in both groups (modified Suanzaoren Decoction group: t=5.29, Z=4.58; estazolam group: t=4.55, Z=3.83) (all voxel-level P<0.001, cluster-level P<0.05, GRF-corrected). No significant pre- versus post-treatment differences were observed in liver or renal function indices in either group (P>0.05). Conclusion Following modified Suanzaoren Decoction and estazolam treatment in CID patients with Yin-deficiency and fire-excess syndrome, the EC between the left inferior parietal lobule of the DMN and both the supplementary motor area and the precuneus exhibited directionally convergent remodeling in both groups.