A novel balanced chromosomal translocation found in subjects with schizophrenia and schizotypal personality disorder: Altered l-serine level associated with disruption of PSAT1 gene expression
Open accessAbstract
l-Serine is required for the synthesis of glycine and d-serine, both of which are NMDA receptor co-agonists. Although roles for d-serine and glycine have been suggested in schizophrenia, little is known about the role of the l-serine synthesizing cascade in schizophrenia or related psychiatric conditions. Here we report a patient with schizophrenia carrying a balanced chromosomal translocation with the breakpoints localized to 3q13.12 and 9q21.2. We examined this proband and her son with schizotypal personality disorder for chromosomal abnormalities, molecular expression profiles, and serum amino acids. Marked decrease of l-serine and glutamate was observed in the sera of the patient and her son, compared with those in normal controls. Interestingly, expression of PSAT1 gene, which is located next to the breakpoint and encodes one of the enzymes in the l-serine synthesizing cascade, was reduced in both patient and her son. Direct effect of impaired PSAT1 gene expression on decreased serum l-serine level was strongly implicated by rat astrocyte experiments. In summary, we propose an idea that PSAT1 may be implicated in altered serine metabolism and schizophrenia spectrum conditions.
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PSAT1 disruption has been linked to schizophrenia.
“whose disruption has been linked to schizophrenia39.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [39]
PSAT1 has been associated with schizophrenia.
“PSAT1, a gene that has been associated with schizophrenia39.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [39]
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Cites
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
(1998) · PubMed · Cited by 10,216 · see citing works
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
The mini international neuropsychiatric interview
Lecrubier, Y., Sheehan, D. V., Hergueta, T., & Weiller, E. (1998) · European Psychiatry · doi:10.1016/s0924-9338(99)80239-9 · Cited by 5,882 · see citing works
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · see citing works
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · see citing works
Wellcome Trust Case Control Consortium, Ferreira, M. A. R., O'Donovan, M. C., Meng, Y. A., Jones, I. R., Ruderfer, D. M., Jones, L., Fan, J., Kirov, G., Perlis, R. H., et al. (2008) · Nature Genetics · doi:10.1038/ng.209 · Cited by 1,237 · see citing works
Self-citationBaum, A. E., Akula, N., Cabanero, M., Cardona, I., Corona, W., Klemens, B., Schulze, T. G., Cichon, S., Rietschel, M., Nöthen, M. M., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002012 · Cited by 700 · see citing works
D-Alanine Added to Antipsychotics for the Treatment of Schizophrenia
Tsai, G. E., Yang, P., Chang, Y., & Chong, M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.032 · Cited by 676 · see citing works
Postpartum mood disorders: diagnosis and treatment guidelines.
Nonacs, R. M., & Cohen, L. S. (1998) · PubMed · Cited by 588 · see citing works
Chumakov, I., Blumenfeld, M., Guerassimenko, O., Cavarec, L., Palicio, M., Abderrahim, H., Bougueleret, L., Barry, C., Tanaka, H., Rosa, P. L., et al. (2002) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.182412499 · Cited by 541 · see citing works
Elia, J., Gai, X., Xie, H. M., Perin, J. C., Geiger, E., Glessner, J. T., D'arcy, M., deBerardinis, R., Frackelton, E., Kim, C., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.57 · Cited by 529 · see citing works
Glutamate as a therapeutic target in psychiatric disorders
Javitt, D. C. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001551 · Cited by 524 · see citing works
Reliability and validity of Japanese version of the Mini‐International Neuropsychiatric Interview
Otsubo, T., Tanaka, K., Koda, R., Shinoda, J., SANO, N., Tanaka, S., AOYAMA, H., Mimura, M., & Kamijima, K. (2005) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2005.01408.x · Cited by 508 · see citing works
Decreased Serum Levels of D-Serine in Patients With Schizophrenia
Hashimoto, K., Fukushima, T., Shimizu, E., Komatsu, N., Watanabe, H., 篠田, 直., Nakazato, M., Kumakiri, C., Okada, S.-I., Hasegawa, H., et al. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.6.572 · Cited by 489 · see citing works
Self-citationOkamoto, N., Hori, S., Akazawa, C., Hayashi, Y., Shigemoto, R., Mizuno, N., & Nakanishi, S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42247-2 · Cited by 462 · see citing works
Heresco‐Levy, U., Javitt, D. C., Ebstein, R. P., Vass, Á., Lichtenberg, P., Bar, G., Catinari, S., & Ermilov, M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.12.037 · Cited by 386 · see citing works
A CSF and postmortem brain study of d-serine metabolic parameters in schizophrenia
Bendikov, I., Nadri, C., Amar, S., Panizzutti, R., DEMIRANDA, J., Wolosker, H., & Agam, G. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.10.010 · Cited by 323 · see citing works
Schumacher, J. H., Jamra, R. A., Freudenberg, J., Becker, T., Ohlraun, S., Otte, A., Tullius, M., Kovalenko, S., Bogaert, A. V. D., Maier, W., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001421 · Cited by 312 · see citing works
Hovatta, I., Varilo, T., Suvisaari, J., Terwilliger, J. D., Ollikainen, V., Arajärvi, R., Juvonen, H., Kokko-Sahin, M.-L., Väisänen, L., Mannila, H., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302567 · Cited by 281 · see citing works
Sarcosine or D-Serine Add-on Treatment for Acute Exacerbation of Schizophrenia
Lane, H., Chang, Y., Liu, Y., Chiu, C., & Tsai, G. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1196 · Cited by 271 · see citing works
High dose D-serine in the treatment of schizophrenia
Kantrowitz, J. T., Malhotra, A. K., Cornblatt, B. A., Silipo, G. S., Balla, A., Suckow, R. F., D’Souza, C., Saksa, J. R., Woods, S. W., & Javitt, D. C. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2010.05.012 · Cited by 253 · see citing works
High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia
Heresco-Levy, U., Ermilov, M., Lichtenberg, P., Bar, G., & Javitt, D. C. (2004) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00707-8 · Cited by 222 · see citing works
Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression
Huang, J., Perlis, R. H., Lee, P. H., Rush, A. J., Fava, M., Sachs, G. S., Lieberman, J., Hamilton, S. P., Sullivan, P., Sklar, P., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09091335 · Cited by 213 · see citing works
3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis.
Jaeken, J., Detheux, M., Maldergem, L. V., Foulon, M., Carchon, H. A., & SCHAFTINGEN, E. V. (1996) · Archives of Disease in Childhood · doi:10.1136/adc.74.6.542 · Cited by 180 · see citing works
Lane, H., Huang, C.-L., Wu, P.-L., Liu, Y., Chang, Y., Lin, P., Chen, P., & Tsai, G. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.005 · Cited by 179 · see citing works
Buchanan, R. W., Freedman, R., Javitt, D. C., Abi‐Dargham, A., & Lieberman, J. A. (2007) · Schizophrenia Bulletin · doi:10.1093/schbul/sbm083 · Cited by 169 · see citing works
Singleton deletions throughout the genome increase risk of bipolar disorder
Zhang, D., Cheng, L., Qian, Y., Alliey-Rodriguez, N., Kelsoe, J. R., Greenwood, T., Nievergelt, C., Barrett, T. B., McKinney, R., Schork, N., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.144 · Cited by 148 · see citing works
Yamada, K., Ohnishi, T., Hashimoto, K., Ohba, H., Iwayama‐Shigeno, Y., Toyoshima, M., Okuno, A., Takao, H., Toyota, T., Minabe, Y., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.018 · Cited by 147 · see citing works
Self-citationDisruption of the neuronal PAS3 gene in a family affected with schizophrenia
Kamnasaran, D., Muir, W. J., Ferguson-Smith, M. A., & Cox, D. W. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.5.325 · Cited by 146 · see citing works
Self-citationSerine racemase binds to PICK1: potential relevance to schizophrenia
Fujii, K., Maeda, K., Hikida, T., Mustafa, A., Balkissoon, R., Xia, J., Yamada, T., Ozeki, Y., Kawahara, R., Okawa, M., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001776 · Cited by 137 · see citing works
Self-citationHeresco‐Levy, U., & Javitt, D. C. (2003) · Schizophrenia Research · doi:10.1016/s0920-9964(03)00129-4 · Cited by 120 · see citing works
Phosphoserine Aminotransferase Deficiency: A Novel Disorder of the Serine Biosynthesis Pathway
Hart, C., Race, V., Achouri, Y., Wiame, E., Sharrard, M. J., Olpin, S. E., Watkinson, J., Bonham, J. R., Jaeken, J., Matthijs, G., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/517888 · Cited by 120 · see citing works
Labrie, V., & Roder, J. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.08.002 · Cited by 116 · see citing works
A Genetic Variant of the Serine Racemase Gene Is Associated with Schizophrenia
Morita, Y., Ujike, H., Tanaka, Y., Otani, K., Kishimoto, M., Morio, A., Kotaka, T., Okahisa, Y., Matsushita, M., Morikawa, A., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.025 · Cited by 112 · see citing works
Hashimoto, K., Engberg, G., Shimizu, E., Nordin, C., Lindström, L., & Iyo, M. (2005) · BMC Psychiatry · doi:10.1186/1471-244x-5-6 · Cited by 106 · see citing works
Self-citationGlycine Transport Inhibitors and the Treatment of Schizophrenia
Javitt, D. C. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.017 · Cited by 100 · see citing works
de Koning, T. D., & Klomp, L. (2004) · Current Opinion in Neurology · doi:10.1097/00019052-200404000-00019 · Cited by 99 · see citing works
Cascella, N. G., Macciardi, F. M., Cavallini, M. C., & Smeraldi, E. (1994) · Journal of Neural Transmission · doi:10.1007/bf01276429 · Cited by 92 · see citing works
Fukushima, T., Kawai, J., Imai, K., & Toyo’oka, T. (2004) · Biomedical Chromatography · doi:10.1002/bmc.394 · Cited by 91 · see citing works
Pickard, B. S., Malloy, M. P., Porteous, D. J., Blackwood, D. H. R., & Muir, W. J. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30204 · Cited by 89 · see citing works
Self-citationde Koning, T. J., Durán, M., DORLAND, L., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440219 · Cited by 85 · see citing works
McInnis, M. G., Dick, D. M., Willour, V. L., et al. (2003) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.08.001 · Cited by 85 · see citing works
Cis-ruption mechanisms: disruption of cis-regulatory control as a cause of human genetic disease
Kleinjan, D., & Coutinho, P. (2009) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elp022 · Cited by 83 · see citing works
Phosphoserine phosphatase deficiency in a patient with Williams syndrome.
Jaeken, J., Detheux, M., Fryns, J. P., Collet, J., Alliet, P. L., & SCHAFTINGEN, E. V. (1997) · Journal of Medical Genetics · doi:10.1136/jmg.34.7.594 · Cited by 76 · see citing works
Saxe, J. P., Wu, H., Kelly, T. K., Phelps, M. E., Sun, Y. E., Kornblum, H. I., & Huang, J. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.07.016 · Cited by 66 · see citing works
What have the genomics ever done for the psychoses?
Gill, M., Donohoe, G. J., & Corvin, A. P. (2009) · Psychological Medicine · doi:10.1017/s0033291709991139 · Cited by 51 · see citing works
Mutations responsible for 3-phosphoserine phosphatase deficiency
Veiga‐da‐Cunha, M., Collet, J., Prieur, B., et al. (2003) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201083 · Cited by 41 · see citing works
3-phosphoglycerate dehydrogenase deficiency in a patient with West syndrome
Pineda, M., Vilaseca, M., Artuch, R., et al. (2000) · Developmental Medicine & Child Neurology · doi:10.1017/s0012162200001171 · Cited by 38 · see citing works
Nakano, I., Dougherty, J. D., Kim, K., Klement, I., Geschwind, D. H., & Kornblum, H. I. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0046 · Cited by 35 · see citing works
Genome-Wide SNP Array Analysis in Patients with Features of Sotos Syndrome
Visser, R., Gijsbers, A. C. J., Ruivenkamp, C. A. L., Karperien, M., Reeser, H. M., Breuning, M. H., Kant, S. G., & Wit, J. M. (2010) · Hormone Research in Paediatrics · doi:10.1159/000284391 · Cited by 25 · see citing works
l-Serine-O-phosphate in the central nervous system
Antflick, J. E., Vetiska, S., Baizer, J. S., Yao, Y., Baker, G. B., & Hampson, D. R. (2009) · Brain Research · doi:10.1016/j.brainres.2009.08.087 · Cited by 13 · see citing works
Chromosomal abnormalities and psychosis
Muir, W. J., Pickard, B. S., & Blackwood, D. (2006) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.106.023895 · Cited by 11 · see citing works
Self-citationCortical Development and Glutamatergic Dysregulation in Schizophrenia
Sawa, A. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.016 · Cited by 10 · see citing works
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- Authors
- Ozeki, Y., Pickard, B. S., Kano, S.-I., Malloy, M. P., Zeledon, M., Sun, D. Q., Fujii, K., Wakui, K., Shirayama, Y., Fukushima, Y., Kunugi, H., Hashimoto, K., Muir, W. J., Blackwood, D. H., & Sawa, A.
- Affiliations
- National Center of Neurology and Psychiatry (JP)
- Johns Hopkins University (US)
- Western General Hospital (GB)
- Dokkyo Medical University (JP)
- Shinshu University (JP)
- Teikyo University Chiba Medical Center (JP)
- Chiba University (JP)
- Royal Edinburgh Hospital (GB)
- Corresponding author
- Sawa, Akira
- ORCID
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 69
- Issue
- 2
- Pages
- 154-160
- ISSN
- 0168-0102 (ISSN-L)
- PMC
- PMC3049551
- OpenAlex
- W2135162164
- Cited by
- 34
- References
- 54
- Citations by year
- 2025: 4 · 2024: 8 · 2023: 2 · 2022: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 3
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Institute of Mental Health (R21MH085226, MH084018, MH085226, RC1MH088753, MH‑088753, P20MH084018, R01MH069853, MH069853)
- National Institute of General Medical Sciences (T32GM007814)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- balanced chromosomal translocation, schizophrenia, schizotypal personality disorder, L-serine, serine metabolism, glutamate, NMDA receptor co-agonist, glycine, D-serine, serum amino acids, astrocytes, schizophrenia spectrum disorders
- MeSH terms
- Transaminases, Animals, Astrocytes, Chromatography, High Pressure Liquid, Chromosomes, Human, Pair 9, Female, Humans, Male, Middle Aged, Pedigree, Schizophrenia, Serine, Translocation, Genetic, Blotting, Western, Gene Expression, Rats, Sprague-Dawley, Age of Onset, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Rats, Gene Knockdown Techniques, Young Adult
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