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Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms: Effects on Antipsychotic Response and Schizophrenia Psychopathology in a Naturalistic Treatment Setting in Two Independent Korean and Italian Samples

Abstract

Introduction

Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. Genetic factors play an important role in both SCZ liability and its treatment outcome. In the present paper, we investigated the effects of several single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved with antipsychotics (APs) mechanisms of action.

Methods

Two independent samples were investigated in the present study. Totals of 176 SCZ subjects and 326 controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian ancestry were recruited and genotyped. SCZ risk and other parameters were also investigated.

Results

Concerning APs response, only a nominal association with HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis, rs9801117 C–rs12668837 C–rs4621754 A haplotype within ESYT2 and NCAPG2 genes was associated with APs response in the same sample. As for secondary outcomes, rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in the Italian sample. In the haplotype analysis, rs2788478 G–rs2657375 T–rs1039621 A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)–rs6459896 A (NCAPG2) haplotypes were associated with SCZ in the same sample. No association was found in the Korean sample. Finally, our exploratory data suggest a possible modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs response to specific symptom clusters.

Conclusion

Our results did not support a primary role for the genes investigated in the APs response. On the other hand, our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ liability. Finally, our exploratory findings may deserve further investigations in specific studies.

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Acknowledgements

This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant Number: HI12C0003). No funding was received for the publication of this article. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

Marco Calabrò, Stefano Porcelli, Concetta Crisafulli, Sheng-Min Wang, Soo-Jung Lee, Changsu Han, Ashwin A. Patkar, Prakash S. Masand, Diego Albani, Ilaria Raimondi, Gianluigi Forloni, Sofia Bin, Alessandro Mattiaccio, Vilma Mantovani, Tae-Youn Jun, Chi-Un Pae, and Alessandro Serretti have nothing to disclose.

Compliance with Ethics Guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. All the patients were informed in detail about the aims and the procedures of the study and they signed an informed consent prior inclusion into the study. The protocol and the informed consent were approved by the local ethical committee (approval number HC10TISI0031).

Data Availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Chi-Un Pae.

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Calabrò, M., Porcelli, S., Crisafulli, C. et al. Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms: Effects on Antipsychotic Response and Schizophrenia Psychopathology in a Naturalistic Treatment Setting in Two Independent Korean and Italian Samples. Adv Ther 34, 1482–1497 (2017). https://doi.org/10.1007/s12325-017-0555-2

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  • DOI: https://doi.org/10.1007/s12325-017-0555-2

Keywords

  • ARC
  • Antipsychotic
  • BDNF
  • ESYT2
  • HOMER1
  • Psychiatry
  • Response
  • Schizophrenia
  • TXNRD2
  • WDR60