Mismatch negativity and clinical trajectories in psychotic disorders: Five-year stability and predictive utility

Background: Mismatch negativity (MMN) is reduced in psychotic disorders and associated with symptoms and functioning. Several studies have posited the MMN as an index of prediction error (PE), a neural signal theorized to give rise to deficits associated with psychotic illness. This mechanism has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear. Method: We examined the five-year stability of MMN amplitude in individuals with established psychotic disorders (cases; N=132) and never-psychotic participants (NP; N=170), as well as longitudinal associations with clinical symptoms and functioning. Results: MMN exhibited good temporal stability (cases, r=.53; never-psychotic, r=.52). In cases, regression models revealed MMN to be a significant predictor of worsening auditory hallucinations (β=.19) and everyday functioning (β=-.13) at follow-up. Meanwhile, initial IQ (β=-.20), negative symptoms (β=.22), and illness severity (β=-1.9) were significant predictors of worsening MMN amplitude five years later. Conclusions: These results imply that MMN measures a neural deficit that is reasonably stable up to five years, and thus is a promising biomarker. Results support disordered cognition and negative symptoms as preceding reduced PE, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time.