Relationship Between Electroencephalography-Based Mismatch Negativity and Antipsychotic Treatment Response in Young People at Clinical High Risk for Psychosis

Background Antipsychotic medications are often used to treat individuals at clinical high risk for psychosis (CHR-P). However, up to 75% of these individuals will not develop psychotic disorders, nor benefit from such treatments. To optimize treatment, it is important to tailor antipsychotic prescriptions based on individual prognostic markers of positive treatment response. We posit that one such marker is mismatch negativity (MMN), which is linked to glutamatergic NMDAR hypofunction—a known abnormality in psychotic disorders. Aims & Objectives This study aimed to examine the relationship between mismatch negativity (MMN) response and antipsychotic treatment outcomes in CHR-P participants. Since first-line antipsychotics minimally affect glutamate neurotransmission, it is hypothesized that individuals with reduced baseline MMN might respond less to these medications. Method Participants engaged in a roving MMN paradigm prior to commencing or when minimally treated with antipsychotic medications. In these paradigms, participants were required to ignore auditory stimuli while simultaneously performing a tactile distractor task. Average baseline electroencephalographic waveforms and peak MMN amplitudes during the performance of this task were quantified at the Fz electrodes. Thirty-one participants’ baseline peak MMN amplitudes were correlated against symptomatic changes between the point of commencing antipsychotic treatment and after eight weeks of antipsychotic treatment. Additionally, the relationship between baseline peak MMN amplitudes and longer-term clinical outcomes was also examined by examining group differences in baseline MMN peak amplitudes between patients who (1) had stable CHR-P status, (2) remitted from CHR-P status, or (3) transitioned to a psychotic episode at 12-month study follow-up. Results Preliminary analyses indicated that there is no significant relationship between MMN peak amplitudes and antipsychotic treatment outcomes after eight weeks of treatment, nor after twelve months of participation in the study. Discussion & Conclusions The null findings obtained in this research may have been impacted upon by limitations in the study design – including small sample sizes in the analyses of short-term antipsychotic response, heterogeneity of the CHR-P population, and the ‘roving’ nature of the MMN paradigm selected. Future analyses should attempt similar analyses with a standard oddball MMN paradigm before making a judgement on the utility of MMN as a biomarker of treatment response.