Relationship between Mismatch Negativity and Antipsychotic Treatment Response in Young People at Clinical High Risk for Psychosis

Background: Antipsychotics are often prescribed to individuals at clinical high risk for psychosis (CHR-P), despite many not developing psychosis or benefiting from treatment. Mismatch negativity (MMN), linked to glutamatergic NMDAR hypofunction, may predict antipsychotic response. We hypothesized that reduced baseline MMN might indicate poorer response to first-line antipsychotics, which minimally affect glutamate neurotransmission.Methods: Thirty-five CHR-P participants from the NAPLS-3 study completed a roving MMN paradigm prior to commencing or when minimally treated with antipsychotic medications. Baseline electroencephalographic waveforms and peak MMN amplitudes were quantified at FCz electrodes. Symptom severity was measured using the Scale of Psychosis-Risk Symptoms (SOPS) at baseline and after eight weeks of treatment. Baseline peak MMN amplitudes were correlated with symptomatic changes.Results: No reliable MMN response was observed in the full CHR-P sample after Bonferroni correction. Peak MMN amplitudes were not significantly associated with changes in symptom severity across any domain. Exploratory analyses in 17 antipsychotic-naïve participants revealed a significant MMN response and a strong positive correlation between peak MMN amplitudes and increases in positive symptom severity.Conclusions: The utility of MMN as a prognostic marker of antipsychotic treatment response in CHR-P individuals remains unclear. Methodological limitations and MMN paradigm design may have influenced results. Further research addressing these issues is needed to clarify MMN's potential in predicting treatment outcomes in the CHR-P population.