# Investigating neural impairments in psychotic disorders using electroencephalography and cortical spheroids

## TL;DR

This study explores how combining brain wave measurements and lab-grown brain cells can reveal early signs of synaptic dysfunction in psychotic disorders like schizophrenia and bipolar disorder.

## Contribution

The novel approach combines in vivo EEG with in vitro cortical spheroids to investigate neurodevelopmental mechanisms in psychosis.

## Key findings

- EEG-based LTP-like plasticity was reduced in individuals with schizophrenia and bipolar disorder.
- Basal respiration was decreased in bipolar disorder spheroids and VGLUT1 levels were reduced in both schizophrenia and bipolar disorder spheroids.
- A positive association was found between EEG-based plasticity and spheroid basal respiration.

## Abstract

Synaptic dysfunction is a candidate mechanism in psychotic disorders, yet the precise underlying substrates remain elusive. We investigated how combining in vivo electroencephalography (EEG) and in vitro human cortical spheroid (hCS)-based methods can further our understanding of psychosis pathophysiology during fetal stages of neurodevelopment. Ten individuals with schizophrenia (SZ) or bipolar disorder (BD; 5 males and 5 females) and five controls (CTRL; 3 males and 2 females) underwent EEG assessments, including long-term potentiation (LTP)-like cortical plasticity and mismatch negativity (MMN). hCS were generated from induced pluripotent stem cells of all participants, and immunohistochemistry, Seahorse bioenergetics and patch-clamp recordings were performed. EEG-based LTP-like plasticity was reduced in individuals with SZ and BD. Basal respiration was decreased in BD hCS and VGLUT1 levels were reduced in both SZ and BD hCS. There was a positive association between EEG-based LTP-like plasticity and hCS basal respiration which survived correction. Our data provide further support for roles of mitochondrial and glutamatergic impairments in the synaptic dysfunction of psychosis and demonstrate the potential of combining EEG- and hCS-based methods for early development mechanistic studies of brain disorders.