title: Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial.
abstract: Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.
authors.affiliation: a Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University , Taichung , Taiwan.|b Tsaotun Psychiatric Center, Ministry of Health and Welfare , Nantou , Taiwan.|c National Changhua University of Education , Changhua , Taiwan.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: d Department of Psychiatry , Changhua Hospital, Ministry of Health and Welfare , Changhua , Taiwan.
authors.forename: Sun-Yuan
authors.initials: SY
authors.lastname: Liang
authors.affiliation: e Department of Mathematics , Tamkang University , Taipei , Taiwan.
authors.forename: Yue-Cune
authors.initials: YC
authors.lastname: Chang
authors.affiliation: d Department of Psychiatry , Changhua Hospital, Ministry of Health and Welfare , Changhua , Taiwan.
authors.forename: Shuo-Yen
authors.initials: SY
authors.lastname: Ting
authors.affiliation: b Tsaotun Psychiatric Center, Ministry of Health and Welfare , Nantou , Taiwan.
authors.forename: Ching-Ling
authors.initials: CL
authors.lastname: Kao
authors.affiliation: c National Changhua University of Education , Changhua , Taiwan.|f Feng-Yuan Hospital, Ministry of Health and Welfare , Taichung , Taiwan.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Wu
authors.affiliation: g Department of Psychiatry , Harbor-UCLA Medical Center , Torrance , CA , USA.
authors.forename: Guochuan E
authors.initials: GE
authors.lastname: Tsai
authors.affiliation: a Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University , Taichung , Taiwan.|h Department of Psychiatry , China Medical University Hospital , Taichung , Taiwan.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001480:Basal Ganglia Diseases / Q000209:etiology; D001565:Benzoates / Q000008:administration & dosage*; D002908:Chronic Disease; D003071:Cognition / Q000187:drug effects*; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012521:Sarcosine / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy*; D009435:Synaptic Transmission / Q000187:drug effects; D013624:Taiwan
chemical_list: D014150:Antipsychotic Agents; D001565:Benzoates; D050487:Glycine Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D003605:D-Amino-Acid Oxidase; D012521:Sarcosine
keywords: NMDA receptor; Schizophrenia; biological psychiatry; cognitive function; psychopharmacology