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 language | English |
|---|---|
| Pages (from-to) | 62-74 |
| Number of pages | 13 |
| Journal | Journal of Molecular Neuroscience |
| Volume | 64 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2018 Jan 1 |
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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 journal › Article
}
TY - JOUR
T1 - Genetic Variants Within Molecular Targets of Antipsychotic Treatment
T2 - Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features
AU - Calabrò, Marco
AU - Porcelli, Stefano
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
AU - Pae, Chi Un
AU - Serretti, Alessandro
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Antipsychotics
KW - Deep phenotyping
KW - Genetics
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85034658714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034658714&partnerID=8YFLogxK
U2 - 10.1007/s12031-017-1002-1
DO - 10.1007/s12031-017-1002-1
M3 - Article
C2 - 29164477
AN - SCOPUS:85034658714
VL - 64
SP - 62
EP - 74
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 1
ER -