Differential genetic associations and expression of PAPST1/SLC35B2 in bipolar disorder and schizophrenia

Akihito Uezato^{1

2}, Daisuke Jitoku², Dai Shimazu^{2

3}, Naoki Yamamoto^{2

4}, Akeo Kurumaji^{2

5}, Yoshimi Iwayama^{6

7}, Tomoko Toyota^{6

8}, Takeo Yoshikawa^{6

9}, Vahram Haroutunian¹⁰, Eduard Bentea¹¹, Jarek Meller¹², Courtney R Sullivan¹³, James H Meador-Woodruff¹⁴, Robert E McCullumsmith^{15

16}, Toru Nishikawa^{17

18}

Affiliations

¹ School of Health and Welfare, International University of Health and Welfare, Tochigi, Japan.
² Department of Psychiatry and Behavioral Sciences, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
³ Musashishinjo-Kokorono Clinic, Kanagawa, Japan.
⁴ Center for Basic Medical Research, and School of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan.
⁵ Shimousa-Nakayama Mental Clinic, Chiba, Japan.
⁶ Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan.
⁷ Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Hyogo, Japan.
⁸ Laboratory for Molecular Pathology of Psychiatric Disorders, RIKEN Center for Brain Science, Saitama, Japan.
⁹ Office of the Center Director, RIKEN Center for Brain Science, Saitama, Japan.
¹⁰ Department of Psychiatry and Neuroscience, The Icahn School of Medicine at Mount Sinai, Bronx, NY, USA.
¹¹ Neurosciences TA Biology, UCB BioPharma SPRL, Braine-l'Alleud, Belgium.
¹² Departments of Environmental Health, Electrical Engineering and Computing Systems and Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹³ Cyagen US Inc., Santa Clara, CA, USA.
¹⁴ Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Alabama, USA.
¹⁵ Department of Neuroscience, University of Toledo, Toledo, OH, USA.
¹⁶ Promedica, Toledo, OH, USA.
¹⁷ Department of Psychiatry and Behavioral Sciences, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. torunishi@med.showa-u.ac.jp.
¹⁸ Department of Pharmacology, Faculty of Medicine, and Pharmacological Research Center, Showa University, 1-5-8, Shinagawa-ku, Tokyo, 142-8555, Japan. torunishi@med.showa-u.ac.jp.

PMID: 35501530
DOI: 10.1007/s00702-022-02503-7

Differential genetic associations and expression of PAPST1/SLC35B2 in bipolar disorder and schizophrenia

Akihito Uezato et al. J Neural Transm (Vienna). 2022 Jul.

. 2022 Jul;129(7):913-924.

doi: 10.1007/s00702-022-02503-7. Epub 2022 May 2.

Authors

Affiliations

¹ School of Health and Welfare, International University of Health and Welfare, Tochigi, Japan.
² Department of Psychiatry and Behavioral Sciences, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
³ Musashishinjo-Kokorono Clinic, Kanagawa, Japan.
⁴ Center for Basic Medical Research, and School of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan.
⁵ Shimousa-Nakayama Mental Clinic, Chiba, Japan.
⁶ Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama, Japan.
⁷ Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Hyogo, Japan.
⁸ Laboratory for Molecular Pathology of Psychiatric Disorders, RIKEN Center for Brain Science, Saitama, Japan.
⁹ Office of the Center Director, RIKEN Center for Brain Science, Saitama, Japan.
¹⁰ Department of Psychiatry and Neuroscience, The Icahn School of Medicine at Mount Sinai, Bronx, NY, USA.
¹¹ Neurosciences TA Biology, UCB BioPharma SPRL, Braine-l'Alleud, Belgium.
¹² Departments of Environmental Health, Electrical Engineering and Computing Systems and Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹³ Cyagen US Inc., Santa Clara, CA, USA.
¹⁴ Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Alabama, USA.
¹⁵ Department of Neuroscience, University of Toledo, Toledo, OH, USA.
¹⁶ Promedica, Toledo, OH, USA.
¹⁷ Department of Psychiatry and Behavioral Sciences, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. torunishi@med.showa-u.ac.jp.
¹⁸ Department of Pharmacology, Faculty of Medicine, and Pharmacological Research Center, Showa University, 1-5-8, Shinagawa-ku, Tokyo, 142-8555, Japan. torunishi@med.showa-u.ac.jp.

PMID: 35501530
DOI: 10.1007/s00702-022-02503-7

Abstract

Lithium's inhibitory effect on enzymes involved in sulfation process, such as inhibition of 3'(2')-phosphoadenosine 5'-phosphate (PAP) phosphatase, is a possible mechanism of its therapeutic effect for bipolar disorder (BD). 3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is translocated from cytosol to Golgi lumen by PAPS transporter 1 (PAPST1/SLC35B2), where it acts as a sulfa donor. Since SLC35B2 was previously recognized as a molecule that facilitates the release of D-serine, a co-agonist of N-methyl-D-aspartate type glutamate receptor, altered function of SLC35B2 might be associated with the pathophysiology of BD and schizophrenia (SCZ). We performed genetic association analyses of the SLC35B2 gene using Japanese cohorts with 366 BD cases and 370 controls and 2012 SCZ cases and 2170 controls. We then investigated expression of SLC35B2 mRNA in postmortem brains by QPCR using a Caucasian cohort with 33 BD and 34 SCZ cases and 34 controls and by in situ hybridization using a Caucasian cohort with 37 SCZ and 29 controls. We found significant associations between three SNPs (rs575034, rs1875324, and rs3832441) and BD, and significantly reduced SLC35B2 mRNA expression in postmortem dorsolateral prefrontal cortex (DLPFC) of BD. Moreover, we observed normalized SLC35B2 mRNA expression in BD subgroups who were medicated with lithium. While there was a significant association of SLC35B2 with SCZ (SNP rs2233437), its expression was not changed in SCZ. These findings indicate that SLC35B2 might be differentially involved in the pathophysiology of BD and SCZ by influencing the sulfation process and/or glutamate system in the central nervous system.

Keywords: Bipolar disorder; Brain mRNA expression; Genetic association; Lithium; PAPST1/SLC35B2; Schizophrenia.

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References

1. Bamne M, Wood J, Chowdari K, Watson AM, Celik C, Mansour H, Klei L, Gur RC, Bradford LD, Calkins ME, Santos AB, Edwards N, Kwentus J, McEvoy JP, Allen TB, Savage RM, Nasrallah HA, Gur RE, Perry RT, Go RC, Devlin B, Yolken R, Nimgaonkar VL (2012) Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure. Schizophr Bull 38(6):1149–1154. https://doi.org/10.1093/schbul/sbs087 - DOI - PubMed - PMC
1. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265. https://doi.org/10.1093/bioinformatics/bth457 - DOI - PubMed
1. Bauer D, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE (2010) Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia. Schizophr Res 117(1):92–98. https://doi.org/10.1016/j.schres.2009.07.025 - DOI - PubMed
1. Benedetti F, Poletti S, Locatelli C, Mazza E, Lorenzi C, Vitali A, Riberto M, Brioschi S, Vai B, Bollettini I, Melloni E, Aggio V, Falini A, De Bartolomeis A, Colombo C (2018) A homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: a multimodal genetic imaging study. Prog Neuropsychopharmacol Biol Psychiatry 81:88–95. https://doi.org/10.1016/j.pnpbp.2017.10.011 - DOI - PubMed
1. Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH (2007) Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 32(9):1888–1902. https://doi.org/10.1038/sj.npp.1301312 - DOI - PubMed

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Differential genetic associations and expression of PAPST1/SLC35B2 in bipolar disorder and schizophrenia

Affiliations

Differential genetic associations and expression of PAPST1/SLC35B2 in bipolar disorder and schizophrenia

Authors

Affiliations

Abstract

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LinkOut - more resources

Full Text Sources

Medical

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Research Materials