中国神经精神疾病杂志2024,Vol.50Issue(9) :540-545.DOI:10.3969/j.issn.1002-0152.2024.09.004

抗精神病药物所致体质量增加患者灰质体积变化的神经影像-转录分析

Molecular basis underlying gray matter volume changes in patients with AIWG:a transcriptome-neuroimaging study

张素贞 蒯新平 高天昊 李旋 卓恺明 项琼 刘登堂
中国神经精神疾病杂志2024,Vol.50Issue(9) :540-545.DOI:10.3969/j.issn.1002-0152.2024.09.004

抗精神病药物所致体质量增加患者灰质体积变化的神经影像-转录分析

Molecular basis underlying gray matter volume changes in patients with AIWG:a transcriptome-neuroimaging study

张素贞 1蒯新平 1高天昊 1李旋 1卓恺明 1项琼 1刘登堂2
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作者信息

  • 1. 上海交通大学医学院附属精神卫生中心(上海 200030)
  • 2. 上海交通大学医学院附属精神卫生中心(上海 200030);复旦大学附属华山医院
  • 折叠

摘要

目的 探索抗精神病药物所致体质量增加的患者脑灰质体积变化及神经机制.方法 收集2019年10月至2021年12月上海市精神卫生中心收治的首发未用药精神分裂症患者129例,根据抗精神病药物治疗8周后体质量变化分为体质量增加组(weight gain,WG)(体质量较基线增加≥7%)和体质量稳定组(weight stable,WS)(体质量较基线变化<3%).在治疗前后评估患者体质量并采集大脑MRI结构像.应用艾伦人脑图谱进行灰质体积改变与基因表达水平的空间相关分析,并进行基因注释分析.结果 纳入33例体质量增加患者和27例体质量稳定患者.与基线比较,WG组治疗后右侧海马、左侧基底节、右侧顶下小叶等脑区灰质体积减小,双侧丘脑灰质体积增加(P<0.05);WS组治疗后双侧眶回、双侧额下回和双侧海马等脑区灰质体积较基线减小(P<0.05),未发现灰质体积增加的脑区.神经影像-转录分析显示354个与WG组灰质体积改变相关的基因,这些基因特异性富集在库欣综合征、神经炎症和谷氨酸信号等通路,特异性表达在表达孤咖啡肽前体的神经元.结论 抗精神病药物所致体质量增加患者丘脑灰质体积增加,且与库欣综合征、表达孤咖啡肽前体的神经元等有关,这为抗精神病药所致体质量增加神经机制提供了新的线索.

Abstract

Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.

关键词

精神分裂症/抗精神病药物/体质量增加/灰质体积/丘脑/艾伦人脑图谱/基因表达

Key words

Schizophrenia/Antipsychotic/Weight gain/Gray matter volume/Thalamus/AHBA/Gene expres-sion

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基金项目

国家自然科学基金面上项目(82371504)

上海交通大学医工交叉研究基金(YG2024QNA55)

出版年

2024
中国神经精神疾病杂志
中山大学

中国神经精神疾病杂志

CSTPCDCSCD北大核心
影响因子:1.38
ISSN:1002-0152
参考文献量36
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