Grant Report on <font style="font-size:14px;">D-</font>Serine Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia-Journal of Psychiatry and Brain Science-CSCIED科技核心评价数据库-手机版

Grant Report on D-Serine Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia

Grant Report on D-Serine Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia

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DOI	10.20900/jpbs.20200018
刊名	Journal of Psychiatry and Brain Science JPBS
年，卷(期)	2020, 5(4)
作者	Natalie de la Garrigue,Juliana Glasser,Pejman Sehatpour,Dan V. Iosifescu,Elisa Dias,Marlene Carlson,Constance Shope,Tarek Sobeih,Tse- Hwei Choo,Melanie M. Wall,Lawrence S. Kegeles,James Gangwisch,Megan Mayer,Stephanie Brazis,Heloise M. De Baun,Stephanie W,
作者单位	New York State Psychiatric Institute, New York, NY 10032, USA ; Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA ; NYU Langone Medical Center, New York, NY 10016, USA ; Nathan Kline Institute, Orangeburg, NY 10962, USA ;
Abstract	We report on the rationale and design of an ongoing NIMH sponsored R61-R33 project in schizophrenia/schizoaffective disorder. This project studies augmenting the efficacy of auditory neuroplasticity cognitive remediation (AudRem) with D-serine, an N-methyl-D-aspartate-type glutamate receptor (NMDAR) glycine-site agonist. We operationalize improved (smaller) thresholds in pitch (frequency) between successive auditory stimuli after AudRem as improved plasticity, and mismatch negativity (MMN) and auditory θ as measures of functional target engagement of both NMDAR agonism and plasticity. Previous studies showed that AudRem alone produces significant, but small cognitive improvements, while D-serine alone improves symptoms and MMN. However, the strongest results for plasticity outcomes (improved pitch thresholds, auditory MMN and θ) were found when combining D-serine and AudRem. AudRem improvements correlated with reading and other auditory cognitive tasks, suggesting plasticity improvements are predictive of functionally relevant outcomes. While D-serine appears to be efficacious for acute AudRem enhancement, the optimal dose remains an open question, as does the ability of combined D-serine + AudRem to produce sustained improvement. In the ongoing R61, 45 schizophrenia patients will be randomized to receive three placebo-controlled, double-blind D-serine + AudRem sessions across three separate 15 subject dose cohorts (80/100/120 mg/kg). Successful completion of the R61 is defined by ≥moderate effect size changes in target engagement and correlation with function, without safety issues. During the three-year R33, we will assess the sustained effects of D-serine + AudRem. In addition to testing a potentially viable treatment, this project will develop a methodology to assess the efficacy of novel NMDAR modulators, using D-serine as a “gold-standard”.
KeyWord	schizophrenia; cognition; auditory remediation; N-methyl-D-aspartate-type glutamate receptor; mismatch negativity; auditory theta
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引用本文

Natalie de la Garrigue,Juliana Glasser,Pejman Sehatpour,Dan V. Iosifescu,Elisa Dias,Marlene Carlson,Constance Shope,Tarek Sobeih,Tse- Hwei Choo,Melanie M. Wall,Lawrence S. Kegeles,James Gangwisch,Megan Mayer,Stephanie Brazis,Heloise M. De Baun,Stephanie W. Grant Report on D-Serine Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia, Journal of Psychiatry and Brain Science. 2020; 5; (4). https://doi.org/10.20900/jpbs.20200018.

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