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脑源性神经营养因子基因rs10835210多态性与童年期虐待对中国男性甲基苯丙胺使用障碍患者认知功能的交互作用

Interactive effect of BDNF rs10835210 polymorphism and childhood maltreatment on cognitive functioning in Chinese male patients with methamphetamine use disorder.

作者信息

Jiang Linjun, Wang Dongmei, Tian Yang, Chen Jiajing, Qu Mengqian, Chen Han, Huang Ren, Jia Lianglun, Fu Fabing, Tang Shanshan, Wang Xiaotao, Zhang Xiang-Yang

机构信息

State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Chaoyang District, Beijing, 100101, China.

Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2025 Jun 28. doi: 10.1007/s00406-025-02038-4.

Abstract

BACKGROUND

Patients with methamphetamine use disorder (MUD) are known to experience cognitive dysfunction. Our previous study was the first to demonstrate the negative impact of childhood maltreatment (CM) on cognitive function in MUD patients. Extensive research has highlighted the crucial role of brain-derived neurotrophic factor (BDNF) gene polymorphisms in cognitive function. However, whether genetic variations in BDNF interact with environmental factors such as CM to influence cognition remains unclear. Therefore, this study aimed to investigate the potential interaction between BDNF gene polymorphism and CM in affecting cognitive function among MUD patients.

METHODS

We recruited 558 MUD patients and 459 healthy controls, assessed cognitive function using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) and CM using the Chinese version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) in all participants, and genotyped all patients and 158 healthy controls for the BDNF rs10835210 polymorphism.

RESULTS

CM negatively affected cognitive performance in both MUD patients and healthy controls, especially in visuospatial/constructional abilities (HC: FDR p < 0.001), attention (HC: FDR p = 0.008; MUD: FDR p < 0.001), and RBANS total score (HC: FDR p < 0.001; MUD: FDR p = 0.006). Furthermore, a significant interaction between CM and the BDNF rs10835210 polymorphism on attention (FDR p = 0.006) was observed in MUD patients, but not in healthy controls. Post hoc analyses revealed that among carriers of the BDNF rs10835210 A allele, MUD patients with CM had lower RBANS attention scores (FDR p < 0.001) than those without CM. In contrast, no significant simple main effect of CM on RBANS attention was found among MUD patients carrying BDNF rs10835210 CC genotype.

CONCLUSIONS

Our findings suggest that CM impairs multiple aspects of cognitive function in MUD patients. Moreover, the BDNF gene rs10835210 polymorphism mediates the effect of CM on cognitive function in this population.

摘要

背景

已知甲基苯丙胺使用障碍(MUD)患者存在认知功能障碍。我们之前的研究首次证明了童年虐待(CM)对MUD患者认知功能的负面影响。广泛的研究强调了脑源性神经营养因子(BDNF)基因多态性在认知功能中的关键作用。然而,BDNF基因变异是否与CM等环境因素相互作用以影响认知仍不清楚。因此,本研究旨在探讨BDNF基因多态性与CM在影响MUD患者认知功能方面的潜在相互作用。

方法

我们招募了558例MUD患者和459名健康对照,使用重复神经心理状态评估量表(RBANS)评估所有参与者的认知功能,使用中文版儿童创伤问卷简表(CTQ-SF)评估CM,并对所有患者和158名健康对照进行BDNF rs10835210多态性基因分型。

结果

CM对MUD患者和健康对照的认知表现均有负面影响,尤其是在视觉空间/构建能力(健康对照:FDR p < 0.001)、注意力(健康对照:FDR p = 0.008;MUD患者:FDR p < 0.001)和RBANS总分(健康对照:FDR p < 0.001;MUD患者:FDR p = 0.006)方面。此外,在MUD患者中观察到CM与BDNF rs10835210多态性在注意力方面存在显著交互作用(FDR p = 0.006),而在健康对照中未观察到。事后分析显示,在BDNF rs10835210 A等位基因携带者中,有CM的MUD患者的RBANS注意力得分(FDR p < 0.001)低于无CM的患者。相比之下,在携带BDNF rs基因型的MUD患者中,未发现CM对RBANS注意力有显著的简单主效应。

结论

我们的研究结果表明,CM损害了MUD患者认知功能的多个方面。此外,BDNF基因rs10835210多态性介导了CM对该人群认知功能的影响。

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