Refining antipsychotic treatment strategies in schizophrenia: discovery of genetic biomarkers for enhanced drug response prediction

被引：0

作者：

Chen, Luan ^{[1
]}

Huai, Cong ^{[1
]}

Song, Chuanfu ^{[2
]}

Wu, Shaochang ^{[3
]}

Xu, Yong ^{[4
,5
]}

Yi, Zhenghui ^{[6
]}

Tang, Jinsong ^{[7
]}

Fan, Lingzi ^{[8
]}

Wu, Xuming ^{[9
]}

Ge, Zhenhua ^{[9
]}

Liu, Chuanxin ^{[10
]}

Jiang, Deguo ^{[11
]}

Weng, Saizheng ^{[12
]}

Wang, Guoqiang ^{[13
]}

Zhang, Xinfeng ^{[14
]}

Zhao, Xudong ^{[15
]}

Shen, Lu ^{[1
,16
]}

Zhang, Na ^{[1
,17
]}

Wu, Hao ^{[1
]}

Wang, Yongzhi ^{[1
]}

Guo, Zhenglin ^{[18
]}

Zhang, Suli ^{[1
]}

Jiang, Bixuan ^{[1
]}

Zhou, Wei ^{[1
,19
,20
]}

Ma, Jingsong ^{[1
]}

Li, Mo ^{[1
]}

Chu, Yunpeng ^{[1
]}

Zhou, Chenxi ^{[1
]}

Lv, Qinyu ^{[6
]}

Xu, Qingqing ^{[6
]}

Zhu, Wenli ^{[2
]}

Zhang, Yan ^{[3
]}

Lian, Weibin ^{[3
]}

Liu, Sha ^{[4
]}

Li, Xinrong ^{[4
]}

Gao, Songyin ^{[8
]}

Liu, Aihong ^{[8
]}

He, Lei ^{[8
]}

Yang, Zhenzhen ^{[10
]}

Dai, Bojian ^{[11
]}

Ye, Jiaen ^{[11
]}

Lin, Ruiqian ^{[12
]}

Lu, Yana ^{[13
]}

Yan, Qi ^{[9
]}

Hu, Yalan ^{[9
]}

Xing, Qinghe ^{[21
,22
]}

Huang, Hailiang ^{[18
,23
,24
]}

Qin, Shengying ^{[1
,17
]}

机构：

[1] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China

[2] Fourth Peoples Hosp Wuhu, Wuhu, Peoples R China

[3] Second Peoples Hosp Lishui, Lishui, Peoples R China

[4] First Hosp Shanxi Med Univ, Shanxi Key Lab Artificial Intelligence Assisted Di, Taiyuan, Peoples R China

[5] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Clin Psychol, Shenzhen, Guangdong, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai, Peoples R China

[7] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Psychiat, Hangzhou, Peoples R China

[8] Zhengzhou Univ, Zhumadian Peoples Hosp 2, Brain Hosp Affiliated, Zhumadian, Peoples R China

[9] Nantong Fourth Peoples Hosp, Nantong, Jiangsu, Peoples R China

[10] Jining Med Univ, Sch Mental Hlth, Dept Psychiat, Jining, Peoples R China

[11] Wenzhou Seventh Peoples Hosp, Wenzhou, Peoples R China

[12] Fujian Med Univ, Dept Psychiat, Fuzhou, Peoples R China

[13] Nanjing Med Univ, Dept Psychiat, Wuxi, Peoples R China

[14] Jingzhou Mental Hlth Ctr, Jingzhou, Peoples R China

[15] Tongji Univ, Sch Med, Shanghai Pudong New Area Mental Hlth Ctr, Shanghai, Peoples R China

[16] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[17] Sichuan Univ Chengdu, Chengdu 610065, Sichuan, Peoples R China

[18] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[19] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Childrens Environm Hlth, Minist Educ, Shanghai, Peoples R China

[20] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Dev & Behav Paediat & Child Primary Care, Shanghai, Peoples R China

[21] Fudan Univ, Inst Pediat, Shanghai 200032, Peoples R China

[22] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[23] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[24] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

来源：

MOLECULAR PSYCHIATRY | 2024年

关键词：

2ND-GENERATION ANTIPSYCHOTICS; TRANSCRIPTION; ASSOCIATION; MEDICATION; DISORDER; BIPOLAR; SETS;

D O I：

10.1038/s41380-024-02841-w

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Schizophrenia (SCZ) is a severe mental disorder affecting around 1% of individuals worldwide. The variability in response to antipsychotic drugs (APDs) among SCZ patients presents a significant challenge for clinicians in determining the most effective medication. In this study, we investigated the biological markers and established a predictive model for APD response based on a large-scale genome-wide association study using 3269 Chinese schizophrenia patients. Each participant underwent an 8-week treatment regimen with one of five mono-APDs: olanzapine, risperidone, aripiprazole, quetiapine, or amisulpride. By dividing the response into ordinal groups of "high", "medium", and "low", we mitigated the bias of unclear treatment outcome and identified three novel significantly associated genetic loci in or near CDH12, WDR11, and ELAVL2. Additionally, we developed predictive models of response to each specific APDs, with accuracies ranging from 79.5% to 98.0%. In sum, we established an effective method to predict schizophrenia patients' response to APDs across three categories, integrating novel biomarkers to guide personalized medicine strategies.

引用

页数：10

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