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 journalArticlepeer-review

    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

    Keywords

    • Antipsychotics
    • Deep phenotyping
    • Genetics
    • Schizophrenia

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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