1. Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis.
- Author
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Hamilton HK, Roach BJ, Bachman PM, Belger A, Carrión RE, Duncan E, Johannesen JK, Light GA, Niznikiewicz MA, Addington J, Bearden CE, Cadenhead KS, Cornblatt BA, Perkins DO, Tsuang MT, Walker EF, Woods SW, Cannon TD, and Mathalon DH
- Abstract
Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity. Therefore, using data collected during the 8-center North American Prodrome Longitudinal Study (NAPLS-2), we explored relationships between MMN amplitudes and salivary cortisol, gray matter volumes, and inflammatory cytokines. Participants included 303 CHR-P individuals with baseline electroencephalography (EEG) data recorded during an MMN paradigm as well as structural magnetic resonance imaging (MRI) and salivary cortisol, of which a subsample (n = 57) also completed blood draws. More deficient MMN amplitudes were associated with greater salivary cortisol and pro-inflammatory cytokine levels in future CHR-Converters, but not among those who did not convert to psychosis within the next two years. More deficient MMN amplitude was also associated with smaller total gray matter volume across participants regardless of future clinical outcomes, and with subcortical gray matter volumes among future CHR-Converters only. These findings are consistent with the theory that deficient NMDAR-dependent plasticity results in an overabundance of weak synapses that are subject to over-pruning during psychosis onset, contributing to gray matter loss. Further, MMN plasticity mechanisms may interact with stress, cortisol, and neuroinflammatory processes, representing a proximal influence of psychosis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Duncan has received research support for work unrelated to this project from Posit Science Inc, Auspex Pharmaceuticals, Teva Pharmaceuticals, and GrayMatters Health. Dr. Johannesen reports grants from the National Institute of Mental Health and received salary support during the conduct of the study and also receives compensation by salary and stock shares from Sage Therapeutics outside the submitted work. Dr. Light reports consulting for Astellas Pharma, NeuroSig, Neurocrine, Boehringer Ingelheim Pharmaceuticals, and Heptares Therapeutics outside the submitted work. Dr. Addington reports grants from the University of Calgary during the conduct of the study. Dr. Bearden reports grants from the National Institute of Mental Health during the conduct of the study and outside the submitted work and served on the scientific advisory board for One Mind outside the submitted work. Dr. Cornblatt reports grants from the National Institute of Mental Health during the conduct of the study. Dr. Perkins is a consultant to Sunovion and Alkermes. Dr Woods reports grants from the National Institute of Mental Health during the conduct of the study and outside the submitted work; grants from Substance Abuse and Mental Health Services Administration, Boehringer Ingelheim, Amarex, Teva, and One Mind outside the submitted work; personal fees from Boehringer Ingelheim, Takeda, and New England Research Institute outside the submitted work; and has a patent for US 8492418 B2 for a method of treating the schizophrenia prodrome issued. Dr. Cannon is a consultant to Boehringer Ingelheim Pharmaceuticals and Lundbeck A/S. No other disclosures were reported.
- Published
- 2024
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