EEG biomarkers of target engagement, therapeutic effect, and disease process
Studies suggest that abnormalities in glutamate and GABA signaling contribute to deficits in schizophrenia and related conditions and that these neurochemical abnormalities produce changes in electroencephalographic (EEG) indices, including event‐related potentials and event‐related power within spe...
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Published in | Annals of the New York Academy of Sciences Vol. 1344; no. 1; pp. 12 - 26 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Blackwell Publishing Ltd
01.05.2015
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Studies suggest that abnormalities in glutamate and GABA signaling contribute to deficits in schizophrenia and related conditions and that these neurochemical abnormalities produce changes in electroencephalographic (EEG) indices, including event‐related potentials and event‐related power within specific frequency ranges. Furthermore, clinical studies suggest that a subset of EEG biomarkers is associated with symptoms. This review addresses the relationship between EEG and behavior in preclinical models of N‐methyl‐d‐aspartate (NMDA)‐receptor hypofunction, as well as how these models can be used to screen therapies. Data from schizophrenia patients are juxtaposed with data from animal models, and EEG and behavioral data from mice with disruption of NMDA receptors in excitatory and/or inhibitory neurons are then compared to the pattern observed in schizophrenia. Also discussed are results following exposure to potential therapeutic agents, including GABAB agonists. Furthermore, evidence demonstrates that elevated resting gamma power is associated with deficits in social interactions. Consistent with elevated baseline noise, excitatory neurons from transgenic mice show increased intrinsic excitability in in vitro–slice patch‐clamp studies across model systems. GABAB receptor agonists reduce this excitability, improve gamma‐band responses, and reverse behavioral deficits in mice. Data suggest that baseline gamma power is associated with social function and GABAB agonists may be useful for schizophrenia. Translational EEG biomarkers reflect target engagement and can contribute to the design of more efficient drug trials, likely accelerating the development of new therapeutics for central nervous system disorders. |
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Bibliography: | ArticleID:NYAS12745 istex:C239272EC7E56529FB433CDA6A568B977E353CB6 ark:/67375/WNG-LZ1QQ57Q-V ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0077-8923 1749-6632 |
DOI: | 10.1111/nyas.12745 |