Researchers at the University of Seville have identified alterations in the cerebral cortex of individuals experiencing psychosis, offering fresh insights into the neurological basis of conditions like schizophrenia and bipolar disorder. The study, published February 20, 2026, details changes in brain structure and function linked to the debilitating symptoms of psychosis, including delusions and hallucinations.
The research team employed a combination of electroencephalography (EEG) and analysis of human cortical spheroids (hCS) – lab-grown models of brain tissue – to investigate synaptic dysfunction, a key suspected mechanism in psychotic disorders. Ten individuals diagnosed with schizophrenia or bipolar disorder, alongside five control subjects, participated in EEG assessments measuring cortical plasticity and mismatch negativity. Researchers then generated hCS from induced pluripotent stem cells derived from each participant.
Findings revealed reduced long-term potentiation (LTP)-like plasticity, a measure of the brain’s ability to strengthen synaptic connections, in individuals with both schizophrenia and bipolar disorder. Further analysis of the hCS showed decreased basal respiration in those with bipolar disorder, and reduced levels of the protein VGLUT1 – crucial for glutamatergic signaling – in both schizophrenia and bipolar disorder groups. A correlation was observed between EEG-based plasticity and basal respiration within the hCS.
These results build upon previous work mapping alterations in brain circuits associated with psychosis. A study published in February 2025 highlighted the involvement of a common brain circuit in the development of psychotic symptoms, characterized by delusions, hallucinations, and disorganized thinking. Further investigation, utilizing magnetoencephalographical source imaging, has indicated that psychotic disorders impact both GABAergic inhibition and glutamatergic excitation via NMDA receptors throughout the cerebral cortex.
The University of Seville study suggests impairments in mitochondrial function and glutamatergic signaling contribute to synaptic dysfunction in psychosis. Notably, the patterns of cortical dynamics observed in individuals experiencing a first episode of psychosis, and those at clinical high risk, were similar. These patterns also mirrored the effects of manipulating GABA-A receptors, suggesting a critical role for this inhibitory neurotransmitter system in the development of psychotic symptoms. The degree to which these patterns resembled GABA-A manipulation effects correlated with positive symptoms, while similarity to NMDA effects correlated with negative symptoms.
Researchers emphasize the potential of combining EEG and hCS-based methods for early mechanistic studies of brain disorders. The Nature publication details the leverage of these combined methods to investigate psychosis pathophysiology during fetal stages of neurodevelopment. The study’s findings do not yet indicate specific therapeutic targets, but provide a foundation for further research into potential interventions.
