Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia
BackgroundMost genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1334335/full |
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| author | Masanobu Kogure Nobuhisa Kanahara Atsuhiro Miyazawa Atsuhiro Miyazawa Yuki Shiko Ikuo Otsuka Koichi Matsuyama Koichi Matsuyama Masayuki Takase Makoto Kimura Makoto Kimura Hiroshi Kimura Hiroshi Kimura Hiroshi Kimura Kiyomitsu Ota Kiyomitsu Ota Keita Idemoto Keita Idemoto Masaki Tamura Masaki Tamura Yasunori Oda Taisuke Yoshida Satoshi Okazaki Fumiaki Yamasaki Yusuke Nakata Yoshinori Watanabe Tomihisa Niitsu Akitoyo Hishimoto Masaomi Iyo |
| author_facet | Masanobu Kogure Nobuhisa Kanahara Atsuhiro Miyazawa Atsuhiro Miyazawa Yuki Shiko Ikuo Otsuka Koichi Matsuyama Koichi Matsuyama Masayuki Takase Makoto Kimura Makoto Kimura Hiroshi Kimura Hiroshi Kimura Hiroshi Kimura Kiyomitsu Ota Kiyomitsu Ota Keita Idemoto Keita Idemoto Masaki Tamura Masaki Tamura Yasunori Oda Taisuke Yoshida Satoshi Okazaki Fumiaki Yamasaki Yusuke Nakata Yoshinori Watanabe Tomihisa Niitsu Akitoyo Hishimoto Masaomi Iyo |
| author_sort | Masanobu Kogure |
| collection | DOAJ |
| description | BackgroundMost genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who respond well to antipsychotic medication have a higher dopamine (DA) state in brain synaptic clefts whereas patients with TRS do not show enhanced DA synthesis/release pathways.Patients and methodsTo examine the contribution (if any) of genetics to TRS, we conducted a genetic association analysis of DA-related genes in schizophrenia patients (TRS, n = 435; non-TRS, n = 539) and healthy controls (HC: n = 489).ResultsThe distributions of the genotypes of rs3756450 and the 40-bp variable number tandem repeat on SLC6A3 differed between the TRS and non-TRS groups. Regarding rs3756450, the TRS group showed a significantly higher ratio of the A allele, whereas the non-TRS group predominantly had the G allele. The analysis of the combination of COMT and SLC6A3 yielded a significantly higher ratio of the putative low-DA type (i.e., high COMT activity + high SLC6A3 activity) in the TRS group compared to the two other groups. Patients with the low-DA type accounted for the minority of the non-TRS group and exhibited milder psychopathology.ConclusionThe overall results suggest that (i) SLC6A3 could be involved in responsiveness to antipsychotic medication and (ii) genetic variants modulating brain DA levels may be related to the classification of TRS and non-TRS. |
| first_indexed | 2024-03-07T21:18:29Z |
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| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-03-07T21:18:29Z |
| publishDate | 2024-02-01 |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-000c164e19fa4d76bf1decb0a70580542024-02-27T16:05:36ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402024-02-011410.3389/fpsyt.2023.13343351334335Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophreniaMasanobu Kogure0Nobuhisa Kanahara1Atsuhiro Miyazawa2Atsuhiro Miyazawa3Yuki Shiko4Ikuo Otsuka5Koichi Matsuyama6Koichi Matsuyama7Masayuki Takase8Makoto Kimura9Makoto Kimura10Hiroshi Kimura11Hiroshi Kimura12Hiroshi Kimura13Kiyomitsu Ota14Kiyomitsu Ota15Keita Idemoto16Keita Idemoto17Masaki Tamura18Masaki Tamura19Yasunori Oda20Taisuke Yoshida21Satoshi Okazaki22Fumiaki Yamasaki23Yusuke Nakata24Yoshinori Watanabe25Tomihisa Niitsu26Akitoyo Hishimoto27Masaomi Iyo28Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDivision of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDoujin-kai Kisarazu Hospital, Kisarazu, JapanBiostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, JapanDepartment of Psychiatry, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDouwa-kai Chiba Hospital, Funabashi, JapanShoushin-kai Mobara Mental Hospital, Mobara, JapanChiba Psychiatric Medical Center, Chiba, JapanDepartment of Psychiatry, Kameda Medical Center, Kamogawa, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan0Gakuji-kai Kimura Hospital, Chiba, Japan1Department of Psychiatry, School of Medicine, International University of Health and Welfare, Narita, JapanDoujin-kai Kisarazu Hospital, Kisarazu, Japan2Choshi-kokoro Clinic, Choshi, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDoujin-kai Kisarazu Hospital, Kisarazu, JapanDoujin-kai Kisarazu Hospital, Kisarazu, Japan3Department of Cognitive Behavioral Psychology, Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDoujin-kai Kisarazu Hospital, Kisarazu, JapanDepartment of Psychiatry, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan4Himorogi Psychiatric Institute, Tokyo, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Psychiatry, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Psychiatry, Chiba University Graduate School of Medicine, Chiba, JapanBackgroundMost genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who respond well to antipsychotic medication have a higher dopamine (DA) state in brain synaptic clefts whereas patients with TRS do not show enhanced DA synthesis/release pathways.Patients and methodsTo examine the contribution (if any) of genetics to TRS, we conducted a genetic association analysis of DA-related genes in schizophrenia patients (TRS, n = 435; non-TRS, n = 539) and healthy controls (HC: n = 489).ResultsThe distributions of the genotypes of rs3756450 and the 40-bp variable number tandem repeat on SLC6A3 differed between the TRS and non-TRS groups. Regarding rs3756450, the TRS group showed a significantly higher ratio of the A allele, whereas the non-TRS group predominantly had the G allele. The analysis of the combination of COMT and SLC6A3 yielded a significantly higher ratio of the putative low-DA type (i.e., high COMT activity + high SLC6A3 activity) in the TRS group compared to the two other groups. Patients with the low-DA type accounted for the minority of the non-TRS group and exhibited milder psychopathology.ConclusionThe overall results suggest that (i) SLC6A3 could be involved in responsiveness to antipsychotic medication and (ii) genetic variants modulating brain DA levels may be related to the classification of TRS and non-TRS.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1334335/fullantipsychoticdopaminepsychosissingle nucleotide polymorphismvariable number of tandem repeats |
| spellingShingle | Masanobu Kogure Nobuhisa Kanahara Atsuhiro Miyazawa Atsuhiro Miyazawa Yuki Shiko Ikuo Otsuka Koichi Matsuyama Koichi Matsuyama Masayuki Takase Makoto Kimura Makoto Kimura Hiroshi Kimura Hiroshi Kimura Hiroshi Kimura Kiyomitsu Ota Kiyomitsu Ota Keita Idemoto Keita Idemoto Masaki Tamura Masaki Tamura Yasunori Oda Taisuke Yoshida Satoshi Okazaki Fumiaki Yamasaki Yusuke Nakata Yoshinori Watanabe Tomihisa Niitsu Akitoyo Hishimoto Masaomi Iyo Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia Frontiers in Psychiatry antipsychotic dopamine psychosis single nucleotide polymorphism variable number of tandem repeats |
| title | Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia |
| title_full | Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia |
| title_fullStr | Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia |
| title_full_unstemmed | Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia |
| title_short | Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia |
| title_sort | association of slc6a3 variants with treatment resistant schizophrenia a genetic association study of dopamine related genes in schizophrenia |
| topic | antipsychotic dopamine psychosis single nucleotide polymorphism variable number of tandem repeats |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1334335/full |
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