Abstract
Neuroscience-guided cognitive training induces significant improvement in cognition in schizophrenia subjects, but the biological mechanisms associated with these changes are unknown. In animals, intensive cognitive activity induces increased brain levels of the NMDA-receptor co-agonist D-serine, a molecular system that plays a role in learning-induced neuroplasticity and that may be hypoactive in schizophrenia. Here, we investigated whether training-induced gains in cognition were associated with increases in serum D-serine in outpatients with schizophrenia. Ninety patients with schizophrenia and 53 healthy controls were assessed on baseline serum D-serine, L-serine, and glycine. Schizophrenia subjects performed neurocognitive tests and were assigned to 50 h of either cognitive training of auditory processing systems (N = 47) or a computer games control condition (N = 43), followed by reassessment of cognition and serum amino acids. At study entry, the mean serum D-serine level was significantly lower in schizophrenia subjects vs. healthy subjects, while the glycine levels were significantly higher. There were no significant changes in these measures at a group level after the intervention. However, in the active training group, increased D-serine was significantly and positively correlated with improvements in global cognition and in Verbal Learning. No such associations were observed in the computer games control subjects, and no such associations were found for glycine. D-Serine may be involved in the neurophysiologic changes induced by cognitive training in schizophrenia. Pharmacologic strategies that target D-serine co-agonism of NMDA-receptor functioning may provide a mechanism for enhancing the behavioral effects of intensive cognitive training.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 63-69 |
| Number of pages | 7 |
| Journal | Schizophrenia Research |
| Volume | 207 |
| DOIs | |
| State | Published - May 2019 |
Bibliographical note
Funding Information:This work was supported by the National Institute of Mental Health (Grant MH073358-01 to SV) and Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro ( FAPERJ ) (Grant E-26/110.305/2014 to RP). RP was a recipient of the Long-Term Fellowship from Human Frontier Science Program. CM was supported by fellowships from FAPERJ and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). The auditory cognitive training software used in this study and all technical support were provided to us free of charge by Posit Science, Inc.
Funding Information:
This work was supported by the National Institute of Mental Health (Grant MH073358-01 to SV) and Funda??o de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) (Grant E-26/110.305/2014 to RP). RP was a recipient of the Long-Term Fellowship from Human Frontier Science Program. CM was supported by fellowships from FAPERJ and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). The auditory cognitive training software used in this study and all technical support were provided to us free of charge by Posit Science, Inc. The authors gratefully acknowledge participants and their families; Prof. C. Craik for kindly allowing us to use the HPLC; and the assistance of T. Babcock, A. Lee, C. Tremblay, S. Suojanen, M. Bens, L. Reese, A.C. Rangel and A. Fantinatti.
Publisher Copyright:
© 2018 Elsevier B.V.
Keywords
- Cognitive remediation
- NMDA receptors
- Neuroplasticity
- Schizophrenia