Symposium: MMN as a translational biomarker of psychosis: from bench-to-bedside-to-real-world community settings
Thursday, Sep 10, 2015
MMN, cortisol, inflammation, and gray matter loss in individuals at clinical high risk for psychosis
Psychiatry, UCSF, San Francisco, CA, United States
Cortisol and neuroinflammation are known to interfere with NMDAr-dependent mechanisms of synaptic plasticity, such as long-term potentiation, but their effects on shorter-term plasticity as reflected by mismatch negativity (MMN) are not known. Deficient neuroplasticity may contribute to weakened synapses that are then over-pruned during the pathogenic cascade underlying the transition to psychosis in individuals at clinical high risk (CHR) for psychosis. This pathogenic model is examined in data from the multi-site NAPLS Study.
Participants were individuals at CHR for psychosis (n=598), including a subgroup who transitioned to psychosis (CHR-T; n=72) and a subgroup who did not transition during a 24-month follow-up period (CHR-NT; n=199), and healthy controls (HC; n=242). Measures included: 1) MRI-based cortical gray matter and ventricular volumes at baseline and 12-months (or post-transition to psychosis), 2) Baseline duration- and pitch-deviant MMN, 3) Baseline inflammatory cytokine (TNF-α, IL-2, IL-6, interferon-γ) and cortisol levels.
CHR-T, relative to CHR-NT and HC, showed faster rates of right prefrontal cortical thinning and third ventricle expansion (p<.01, FDR cluster-corrected), smaller MMN amplitudes (p<.05), and elevated cortisol (p<.05). Reduced MMN was associated with higher inflammatory cytokine (r=.48, p<.01) and cortisol (r=.34, p<.01) levels, and faster prefrontal cortical thinning (r= -.36, p<.05) and third ventricle expansion (r=.41, p<.05), in CHR-T, but not CHR-NT.
Thus, MMN deficits increase risk for psychosis and are associated with increased cortisol and inflammatory cytokines and faster cortical thinning in CHR individuals who transition to psychosis.