TY - JOUR
T1 - A novel balanced chromosomal translocation found in subjects with schizophrenia and schizotypal personality disorder
T2 - Altered l-serine level associated with disruption of PSAT1 gene expression
AU - Ozeki, Yuji
AU - Pickard, Benjamin S.
AU - Kano, Shinichi
AU - Malloy, Mary P.
AU - Zeledon, Mariela
AU - Sun, Daniel Q.
AU - Fujii, Kumiko
AU - Wakui, Keiko
AU - Shirayama, Yukihiko
AU - Fukushima, Yoshimitsu
AU - Kunugi, Hiroshi
AU - Hashimoto, Kenji
AU - Muir, Walter J.
AU - Blackwood, Douglas H.
AU - Sawa, Akira
N1 - Funding Information:
We thank Ms. K. Yuasa, supervisor of guardian of adult for the patient, for supporting our project; Dr. M. Honda for introducing us to the patient; Drs. Do Youn Jun and Young Ho Kim for PSAT1 antibody; Ms. Yukiko Lema for organizing the manuscript; and Dr. Pamela Talalay for critically reading the manuscript. This work was supported by a Grant-in-Aid for Scientific Research (C) from the Japanese Society for the Promotion of Science (JSPS) KAKENHI21591492 (Y.O.), U.S. Public Heath Service Grant MH-069853 (A.S.), Silvio O. Conte Center grant MH-084018 (A.S.), MH-085226 (A.S.), MH-088753 (A.S.), and foundation grants from Stanley (A.S.), S-R (A.S.), RUSK (A.S.), as well as NARSAD (A.S). B.S.P. held a Sim Fellowship from the Royal College of Physicians in Edinburgh. The cytogenetics component of the work was supported by a grant from the Chief Scientist Office of the Scottish Government. S.-I.K. was supported by Uehara Memorial Foundation and Kanae Foundataion for the Promotion of Medical Science, and is currently a JSPS Postdoctoral Fellow for Research Abroad.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Balanced chromosomal translocation
KW - D-Serine
KW - Expression
KW - Glutamate
KW - Glycine
KW - L-Serine
KW - PSAT1
KW - Schizophrenia
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U2 - 10.1016/j.neures.2010.10.003
DO - 10.1016/j.neures.2010.10.003
M3 - Article
C2 - 20955740
AN - SCOPUS:78650307890
VL - 69
SP - 154
EP - 160
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 2
ER -