Domestic researchers have revealed that meaningless repetitive behaviors observed in patients with autism or obsessive-compulsive disorder are caused by brain inflammation. While searching for the causes of these repetitive disorders, they also discovered drugs that can suppress the symptoms.
The research team led by Professor Um Ji-won of the Daegu Gyeongbuk Institute of Science and Technology reported on the 12th that they identified the causes of chronic brain inflammation that leads to repetitive behavior disorders and the molecular mechanisms involved.
Repetitive behavior is a common action that anyone can experience once or twice, but if the symptoms worsen, it can lead to autism spectrum disorder or obsessive-compulsive disorder. Until now, it was mainly assumed that abnormal neural circuits or genetic factors were the causes, and a direct correlation between brain inflammation and these behaviors had not been established.
The research team conducted experiments using mice with a mutation in the NLRP3 gene, which triggers inflammatory responses. This gene stimulates microglia, the immune cells in the brain, to sustain chronic inflammation.
As inflammation continued, the 'NMDA (N-methyl-D-aspartate) glutamate receptor,' which is important for excitatory neurotransmission, was excessively activated, clearly resulting in symptoms of repeated meaningless behavior or anxiety.
The research team focused on the excessive activation of the NMDA glutamate receptor as the cause of repetitive behavior. They administered a drug called 'memantine,' one of the existing treatments for Alzheimer’s disease, to the mice with the NLRP3 gene mutation. As a result, the symptoms of meaningless behavior that had been continually repeated significantly decreased, and the activation of NMDA glutamate returned to normal levels. This demonstrated that the overactivity of the NMDA glutamate receptor is the direct cause of the repetitive behavior.
The research team also found clues on how brain inflammation stimulates the NMDA glutamate receptor. They discovered that microglia in an inflammatory state secrete an inflammatory substance (cytokine) called interleukin-1 beta (IL-1β), which affects the NMDA glutamate receptor.
Memantine and interleukin-1RA used in this study are approved treatments by the U.S. Food and Drug Administration (FDA). This means they have found drugs that can be used to treat autism or obsessive-compulsive disorder without developing new drugs.
Professor Um Ji-won noted, “This study is a case demonstrating that chronic brain inflammation induces the overactivation of the NMDA glutamate receptor, which in turn leads to repetitive behavior disorders,” and added, “It could suggest a new therapeutic approach for treating autism spectrum disorder and obsessive-compulsive disorder, which are primarily accompanied by repetitive behaviors.”
References
Cell Reports (2025), DOI : https://doi.org/10.1016/j.celrep.2025.115656