Abstract | CONTEXT: OBJECTIVES: To examine whether plasma levels of pentosidine and serum vitamin B(6) are altered in patients with schizophrenia and to evaluate the functionality of GLO1 variations linked to concomitant carbonyl stress. DESIGN: An observational biochemical and genetic analysis study. SETTING: Multiple centers in Japan. PARTICIPANTS: One hundred six individuals (45 schizophrenic patients and 61 control subjects) were recruited for biochemical measurements. Deep resequencing of GLO1 derived from peripheral blood or postmortem brain tissue was performed in 1761 patients with schizophrenia and 1921 control subjects. MAIN OUTCOME MEASURES:
Pentosidine and vitamin B(6) concentrations were determined by high-performance liquid chromatographic assay. Protein expression and enzymatic activity were quantified in red blood cells and lymphoblastoid cells using Western blot and spectrophotometric techniques. RESULTS: We found that a subpopulation of individuals with schizophrenia exhibit high plasma pentosidine and low serum pyridoxal ( vitamin B(6)) levels. We also detected genetic and functional alterations in GLO1. Marked reductions in enzymatic activity were associated with pentosidine accumulation and vitamin B(6) depletion, except in some healthy subjects. Most patients with schizophrenia who carried the genetic defects exhibited high pentosidine and low vitamin B(6) levels in contrast with control subjects with the genetic defects, suggesting the existence of compensatory mechanisms. CONCLUSIONS:
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Authors | Makoto Arai, Hiroko Yuzawa, Izumi Nohara, Tetsuo Ohnishi, Nanako Obata, Yoshimi Iwayama, Seiichi Haga, Tomoko Toyota, Hiroshi Ujike, Mayumi Arai, Tomoe Ichikawa, Atsushi Nishida, Yoko Tanaka, Aizo Furukawa, Yuuzou Aikawa, Osamu Kuroda, Kazuhiro Niizato, Ryosuke Izawa, Kazuhiko Nakamura, Norio Mori, Daisuke Matsuzawa, Kenji Hashimoto, Masaomi Iyo, Ichiro Sora, Masaaki Matsushita, Yuji Okazaki, Takeo Yoshikawa, Toshio Miyata, Masanari Itokawa |
Journal | Archives of general psychiatry
(Arch Gen Psychiatry)
Vol. 67
Issue 6
Pg. 589-97
(Jun 2010)
ISSN: 1538-3636 [Electronic] United States |
PMID | 20530008
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Glycation End Products, Advanced
- Vitamin B 6
- Arginine
- pentosidine
- Lactoylglutathione Lyase
- Lysine
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Topics |
- Arginine
(analogs & derivatives, blood)
- Biomarkers
(blood, metabolism)
- Chromatography, High Pressure Liquid
- Female
- Glycation End Products, Advanced
(blood, metabolism)
- Humans
- Lactoylglutathione Lyase
(genetics)
- Lysine
(analogs & derivatives, blood)
- Male
- Middle Aged
- Oxidative Stress
(genetics)
- Schizophrenia
(blood, genetics, metabolism)
- Vitamin B 6
(blood)
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