Altered glutamate signaling tied to variants of a protein called Thorase has been associated with schizophrenia, and the antiseizure medication perampanel might help regulate such deficits, a study showed.
“Perampanel treatment … could offer a potential therapeutic opportunity for treating disorders associated with abnormal AMPAR-mediated neurotransmission,” wrote, of Johns Hopkins University, Baltimore, and his associates. AMPARs, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, mediate rapid synaptic transmission in the brain.
The conclusions are based on bidirectional sequence data from a group of adults with schizophrenia and controls, and a murine study.
In the human portion of the study, the researchers analyzed bidirectional sequence data for ATAD1, a protein that codes for Thorase in an Ashkenazi Jewish population. In 712 schizophrenia patients and 649 healthy patients, Dr. Umanah and his associates found three rare gene variants in five individuals. The variants, R9H and D221H, were present only in the patients with schizophrenia. Another variant, E290K, was present in schizophrenia patients as well as in unscreened individuals. The researchers said that the variants found in this analysis might be implicated in schizophrenia.
Building on the observations from the human portion of the study, Dr. Umanah and his colleagues conducted a battery of tests to see whether the observed Thorase variants had any psychological effects on mice that were heterozygous for these variants. The researchers found that these heterozygous Thorase mice were sensitive to psychostimulants, and exhibited impaired memory and social behaviors. Heterozygous Thorase mice also displayed long-term memory and associative learning deficits. Those deficits improved, however, after perampanel was administered.
This study was supported in part by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. The authors declared that they have no conflicts of interest.
Read the full study in Science Translational Medicine (2017 Dec 13;9. doi:).