Excitation/inhibition imbalance and conversion to psychosis in the clinical high risk syndrome: Biophysical modeling finds reduced pyramidal cell excitability across EEG paradigms.

ABSTRACT:

Background

Reduced mismatch negativity (MMN) and P300 event-related potential (ERP) components are widely replicated in schizophrenia and are also observed in individuals at clinical high risk for psychosis (CHR-P) who subsequently convert to psychosis. It is unknown whether they reflect changes in excitatory and/or inhibitory synaptic function, both implicated in schizophrenia and considered potential drug targets.

Methods

We analyzed baseline MMN and P300 ERPs from the NAPLS2 study, asking whether altered synaptic excitation, inhibition, or both could explain amplitude reductions in CHR-P (n=583). CHR-P participants who converted to psychosis (CHR-Converters; n=77) or remitted by 24-month follow-up (CHR-Remitters; n=94) were compared on MMN evoked by pitch+duration double-

SUBMITTER: Rodriguez-Sanchez J 

PROVIDER: S-EPMC12458603 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature