Xie Yuanjun, Guan Muzhen, Zhang Tian, Ma Chaozong, Li Chenxi, Wang Lingling, Lin Xinxin, Li Yijun, Wang Zhongheng, Zhujing Ma, Wang Huaning, Fang Peng
Military Medical Psychology School, Air Force Medical University, Xi'an, China.
Deparment of Mental Health, Xi'an Medical College, Xi'an, China.
Transl Psychiatry. 2025 Jul 10;15(1):237. doi: 10.1038/s41398-025-03459-4.
Auditory verbal hallucinations (AVH) represent a substantial therapeutic challenge in schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in reducing AVH, yet the underlying neurobiological mechanisms remain incompletely understood. This study investigated the genetic and molecular processes associated with functional connectivity density (FCD) changes induced by 1 Hz rTMS in schizophrenia patients with AVH. The results revealed that the active stimulation group exhibited significant improvement in positive symptoms and AVH severity compared to the sham control group. Specifically, rTMS increased FCD within the frontoparietal network while decreasing FCD in the language network. Notably, baseline FCD values in these networks were predictive of the extent of symptom amelioration. Gene enrichment analysis indicated that rTMS-induced FCD changes were linked to molecular pathways critical for cellular homeostasis and neuronal function. Among the identified hub genes, GAL emerged as a key regulator of these alternations. Furthermore, neurotransmitter systems were implicated, with alterations in mu-opioid (MU) receptor density mediating the effects of GAL on FCD modifications. These findings highlight a multifaceted interplay among genetic, molecular, and connectivity-based mechanisms underlying the therapeutic efficacy of rTMS in treating AVH.
听觉言语幻觉（AVH）是精神分裂症治疗中的一项重大挑战。低频重复经颅磁刺激（rTMS）已显示出减轻AVH的潜力，但其潜在的神经生物学机制仍未完全明确。本研究调查了1赫兹rTMS对伴有AVH的精神分裂症患者功能连接密度（FCD）变化所引发的遗传和分子过程。结果显示，与假刺激对照组相比，主动刺激组的阳性症状和AVH严重程度有显著改善。具体而言，rTMS增加了额顶网络内的FCD，同时降低了语言网络中的FCD。值得注意的是，这些网络中的基线FCD值可预测症状改善程度。基因富集分析表明，rTMS诱导的FCD变化与细胞内稳态和神经元功能的关键分子途径相关。在已识别的枢纽基因中，GAL成为这些变化的关键调节因子。此外，神经递质系统也参与其中，μ-阿片（MU）受体密度的改变介导了GAL对FCD修饰的影响。这些发现突出了rTMS治疗AVH疗效背后基于遗传、分子和连接性机制的多方面相互作用。
