Neurophysiological Effects of Bitopertin in Schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• N-methyl-D-aspartate receptor (NMDAR) dysfunction is linked to schizophrenia symptoms and cognitive deficits.
• Auditory mismatch negativity (MMN) is an event-related potential measure sensitive to NMDAR function.
• Previous research suggests glutamate-based interventions may impact NMDAR-related measures.

Purpose of the Study:

• To investigate the effects of bitopertin, a selective glycine transport inhibitor, on NMDAR-related event-related potential deficits in schizophrenia.
• To assess bitopertin's impact on auditory mismatch negativity (MMN) in patients with schizophrenia.
• To evaluate secondary effects on clinical symptoms and neurocognitive performance.

Main Methods:

• A double-blind, parallel-group study treated 29 patients with schizophrenia/schizoaffective disorder with 10 mg of bitopertin.
• Auditory mismatch negativity (MMN) was the primary outcome measure.
• Clinical symptoms and neurocognitive performance were assessed as secondary outcomes.

Main Results:

• Bitopertin treatment did not yield significant changes in neurophysiological assessments, including MMN.
• No significant improvements were observed in clinical symptom ratings.
• Neurocognitive performance remained unchanged following bitopertin administration.

Conclusions:

• This study provides the first assessment of bitopertin's effects on neurophysiological biomarkers in schizophrenia.
• Bitopertin, at the tested dose of 10 mg, did not significantly alter symptoms or NMDAR-related biomarkers.
• The high test-retest reliability of mismatch negativity supports its utility as a target engagement measure in future studies.