Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features

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, Carlotta Cristalli, Vilma Mantovani, Chi Un Pae, Alessandro Serretti

Research output: Contribution to journalArticle

Abstract

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.

Original languageEnglish
Pages (from-to)62-74
Number of pages13
JournalJournal of Molecular Neuroscience
Volume64
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Antipsychotic Agents
Schizophrenia
Age of Onset
Genes
Therapeutics
Mental Disorders
Suicide
Single Nucleotide Polymorphism

Keywords

  • Antipsychotics
  • Deep phenotyping
  • Genetics
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Genetic Variants Within Molecular Targets of Antipsychotic Treatment : Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features. / Calabrò, Marco; Porcelli, Stefano; Crisafulli, Concetta; Wang, Sheng Min; Lee, Soo Jung; Han, Changsu; Patkar, Ashwin A.; Masand, Prakash S.; Albani, Diego; Raimondi, Ilaria; Forloni, Gianluigi; Bin, Sofia; Cristalli, Carlotta; Mantovani, Vilma; Pae, Chi Un; Serretti, Alessandro.

In: Journal of Molecular Neuroscience, Vol. 64, No. 1, 01.01.2018, p. 62-74.

Research output: Contribution to journalArticle

Calabrò, M, Porcelli, S, Crisafulli, C, Wang, SM, Lee, SJ, Han, C, Patkar, AA, Masand, PS, Albani, D, Raimondi, I, Forloni, G, Bin, S, Cristalli, C, Mantovani, V, Pae, CU & Serretti, A 2018, 'Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features', Journal of Molecular Neuroscience, vol. 64, no. 1, pp. 62-74. https://doi.org/10.1007/s12031-017-1002-1
Calabrò, Marco ; Porcelli, Stefano ; Crisafulli, Concetta ; Wang, Sheng Min ; Lee, Soo Jung ; Han, Changsu ; Patkar, Ashwin A. ; Masand, Prakash S. ; Albani, Diego ; Raimondi, Ilaria ; Forloni, Gianluigi ; Bin, Sofia ; Cristalli, Carlotta ; Mantovani, Vilma ; Pae, Chi Un ; Serretti, Alessandro. / Genetic Variants Within Molecular Targets of Antipsychotic Treatment : Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features. In: Journal of Molecular Neuroscience. 2018 ; Vol. 64, No. 1. pp. 62-74.
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AU - Crisafulli, Concetta

AU - Wang, Sheng Min

AU - Lee, Soo Jung

AU - Han, Changsu

AU - Patkar, Ashwin A.

AU - Masand, Prakash S.

AU - Albani, Diego

AU - Raimondi, Ilaria

AU - Forloni, Gianluigi

AU - Bin, Sofia

AU - Cristalli, Carlotta

AU - Mantovani, Vilma

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AU - Serretti, Alessandro

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