In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of D-amino acids by blocking their metabolism. Sodium benzoate is a D-amino acid oxidase inhibitor.OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia.
DESIGN, SETTING, AND PARTICIPANTSA randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo.
MAIN OUTCOMES AND MEASURESThe primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment.RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects.
CONCLUSIONS AND RELEVANCEBenzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT 00960219
A new magnetic nanoparticle was synthesized in the form of Gd(3+)-chelated Fe(3)O(4)@SiO(2). The Fe(3)O(4) nanoparticle was octahedron-structured, was highly magnetic (∼94 emu/g), and was the core of an encapsulating mesoporous silica shell. DOTA-NHS molecules were anchored to the interior channels of the porous silica to chelate Gd(3+) ions. Because there were Gd(3+) ions within the silica shell, the transverse relaxivity increased 7-fold from 97 s(-1) mM(-1) of Fe(3)O(4) to 681 s(-1) mM(-1) of Gd(3+)-chelated Fe(3)O(4)@SiO(2) nanoparticles with r(2)/r(1) = 486. The large transversal relaxivity of the Gd(3+)-chelated Fe(3)O(4)@SiO(2) nanoparticles had an effective magnetic resonance imaging effect and clearly imaged lymph nodes. Physiological studies of liver, spleen, kidney, and lung tissue in mice infused with these new nanoparticles showed no damage and no cytotoxicity in Kupffer cells, which indicated that Gd(3+)-chelated Fe(3)O(4)@SiO(2) nanoparticles are biocompatible.
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