Neuroscience Bulletin

, Volume 35, Issue 6, pp 1102–1105 | Cite as

Interaction Between Variations in Dopamine D2 and Serotonin 2A Receptor is Associated with Short-Term Response to Antipsychotics in Schizophrenia

  • Liansheng Zhao
  • Huijuan Wang
  • Yamin Zhang
  • Jinxue Wei
  • Peiyan Ni
  • Hongyan Ren
  • Gang Li
  • Qiang Wang
  • Gavin P Reynolds
  • Weihua Yue
  • Wei Deng
  • Hao Yan
  • Liwen Tan
  • Qi Chen
  • Guigang Yang
  • Tianlan Lu
  • Lifang Wang
  • Fuquan Zhang
  • Jianli Yang
  • Keqing Li
  • Luxian Lv
  • Qingrong Tan
  • Yinfei Li
  • Hua Yu
  • Hongyan Zhang
  • Xin Ma
  • Fude Yang
  • Lingjiang Li
  • Chuanyue Wang
  • Huiyao Wang
  • Xiaojing Li
  • Wanjun Guo
  • Xun Hu
  • Yang Tian
  • Xiaohong Ma
  • Jeremy Coid
  • Dai Zhang
  • Chao ChenEmail author
  • Tao LiEmail author
  • Chinese Antipsychotics Pharmacogenomics Consortium
Letter to the Editor

Dear Editor,

Schizophrenia is a chronic and debilitating brain disorder, which has a strong genetic component with heritability ranging from 66% to 85% [1, 2]. Currently, antipsychotic drugs remain the most effective treatment for the psychotic symptoms of schizophrenia [3]. Because of the severe side-effects of first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs) have become more widely used in the treatment of schizophrenia. However, due to differing clinical, demographic, environmental, and genetic factors, the treatment response to SGAs shows considerable differences among patients. Most SGAs are antagonists of dopamine D2 (DRD2) and serotonin 2A (5-HT2A) receptors. It has been reported that DRD2 and 5-HT2A receptors play critical roles in antipsychotic effects. Several studies have shown that polymorphisms of the DRD2 and 5-HT2A receptor genes are associated with the antipsychotic response in schizophrenia. However, findings remain inconsistent and even...



This work was supported by the National Basic Research Development Program (2016YFC0904300), the National Natural Science Foundation of China (81630030 and 81461168029), and the 1.3.5 Project for Disciplines of Excellence of West China Hospital, Sichuan University (ZY2016103 and ZY2016203), China.

Conflict of interest

All authors claim that there are no conflicts of interest.

Supplementary material

12264_2019_432_MOESM1_ESM.pdf (181 kb)
Supplementary material 1 (PDF 182 kb)


  1. 1.
    Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe’Er I, et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009, 460: 753–757.CrossRefGoogle Scholar
  2. 2.
    Luan ZL, Cui XH, Xu H, Lu HY, Li YY, Lu TL, et al. Association of MSI2 gene polymorphism with age-at-onset of schizophrenia in a Chinese population. Neurosci Bull 2017, 33: 731–733.CrossRefGoogle Scholar
  3. 3.
    Takekita Y, Fabbri C, Kato M, Nonen S, Sakai S, Sunada N, et al. HTR1A gene polymorphisms and 5-HT1A receptor partial agonist antipsychotics efficacy in schizophrenia. J Clin Psychopharmacol 2015, 35: 220–227.CrossRefGoogle Scholar
  4. 4.
    Neville MJ, Johnstone EC, Walton RT. Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat 2004, 23: 540–545.CrossRefGoogle Scholar
  5. 5.
    Pohjalainen T, Rinne J, Någren K, Lehikoinen P, Anttila K, Syvälahti E, et al. The A1 allele of the human D 2 dopamine receptor gene predicts low D 2 receptor availability in healthy volunteers. Mol Psychiatry 1998, 3: 256–260.CrossRefGoogle Scholar
  6. 6.
    Zhang JP, Lencz T, Malhotra AK. D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis. Am J Psychiatry 2010, 167: 763–772.CrossRefGoogle Scholar
  7. 7.
    Gamazon ER, Segrè AV, van de Bunt M, Wen X, Xi HS, Hormozdiari F, et al. Using an atlas of gene regulation across 44 human tissues to inform complex disease-and trait-associated variation. Nat Genet 2018, 50: 956–967.CrossRefGoogle Scholar
  8. 8.
    Need AC, Keefe RS, Ge D, Grossman I, Dickson S, McEvoy JP, et al. Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. Eur J Hum Genet 2009, 17: 946–957.CrossRefGoogle Scholar
  9. 9.
    Ji X, Takahashi N, Saito S, Ishihara R, Maeno N, Inada T, et al. Relationship between three serotonin receptor subtypes (HTR3A, HTR2A and HTR4) and treatment-resistant schizophrenia in the Japanese population. Neurosci Lett 2008, 435: 95–98.CrossRefGoogle Scholar
  10. 10.
    Mcmahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, et al. Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 2006, 78: 804–814.CrossRefGoogle Scholar
  11. 11.
    Lin JY, Jiang MY, Kan ZM, Chu Y. Influence of 5-HTR2A genetic polymorphisms on the efficacy of antidepressants in the treatment of major depressive disorder: A meta-analysis. J Affect Disord 2014, 168: 430–438.CrossRefGoogle Scholar
  12. 12.
    Staeker J, Leucht S, Laika B, Steimer W. Polymorphisms in serotonergic pathways influence the outcome of antidepressant therapy in psychiatric inpatients. Genet Test Mol Biomarkers 2014, 18: 20–31.CrossRefGoogle Scholar
  13. 13.
    Laika B, Leucht S, Heres S, Schneider H, Steimer W. Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome. Pharmacogenomics J 2010, 10: 20–29.CrossRefGoogle Scholar
  14. 14.
    Noro M, Antonijevic I, Forray C, Kasper S, Kocabas NA, Lecrubier Y, et al. 5HT1A and 5HT2A receptor genes in treatment response phenotypes in major depressive disorder. Int Clin Psychopharmacol 2010, 25: 228–231.CrossRefGoogle Scholar
  15. 15.
    Pitychoutis PM, Belmer A, Moutkine I, Adrien J, Maroteaux LJN. Mice lacking the serotonin Htr 2B receptor gene present an antipsychotic-sensitive schizophrenic-like phenotype. Neuropsychopharmacology 2015, 40: 2764–2773.CrossRefGoogle Scholar
  16. 16.
    Selvaraj S, Arnone D, Cappai A, Howes OJN, Reviews B. Alterations in the serotonin system in schizophrenia: a systematic review and meta-analysis of postmortem and molecular imaging studies. Neurosci Biobehav Rev 2014, 45: 233–245.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  1. 1.Psychiatric Laboratory and Mental Health Center, the State Key Laboratory of BiotherapyWest China Hospital of Sichuan UniversityChengduChina
  2. 2.West China Brain Research CenterWest China Hospital of Sichuan UniversityChengduChina
  3. 3.The National Engineering Research Center for Miniaturized Detection Systems, College of Life ScienceNorthwest UniversityXi’anChina
  4. 4.Shaanxi Lifegen Co., LtdXi’anChina
  5. 5.Biomolecular Science Research CentreSheffield Hallam UniversitySheffieldUK
  6. 6.Peking University Sixth Hospital (Institute of Mental Health)BeijingChina
  7. 7.National Clinical Research Center for Mental Disorders and Key Laboratory of Mental HealthMinistry of Health (Peking University)BeijingChina
  8. 8.Second Xiangya HospitalCentral South UniversityChangshaChina
  9. 9.Beijing Anding Hospital, Beijing Institute for Brain DisordersCapital Medical UniversityBeijingChina
  10. 10.Beijing HuiLongGuan HospitalBeijingChina
  11. 11.Wuxi Mental Health CenterNanjing Medical UniversityWuxiChina
  12. 12.Institute of Mental HealthTianjin Anding HospitalTianjinChina
  13. 13.Tianjin Medical University General HospitalTianjin Medical UniversityTianjinChina
  14. 14.Hebei Mental Health CenterBaodingChina
  15. 15.Second Affiliated Hospital of Xinxiang Medical UniversityXinxiangChina
  16. 16.Department of Psychiatry, Xijing HospitalFourth Military Medical UniversityXi’anChina
  17. 17.Huaxi BiobankWest China Hospital of Sichuan UniversityChengduChina

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