Symposium: MMN as a translational biomarker of psychosis: from bench-to-bedside-to-real-world community settings
Thursday, Sep 10, 2015
Hörsaal 3

MMN, cortisol, inflammation, and gray matter loss in individuals at clinical high risk for psychosis

Daniel Mathalon

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.