An imbalance between antioxidants and harmful molecules in the body is strongly linked to abnormal repetitive behaviors in mice, according to a new study from Stanford University. The research, published on November 5, 2025, in the journal *PLOS One*, identifies several biological markers of this imbalance, known as oxidative stress, and suggests a potential avenue for understanding and treating similar behaviors in humans. The findings could have significant implications for neurodevelopmental and psychiatric conditions that involve repetitive behaviors, such as autism spectrum disorder and schizophrenia.
The study, led by Kendall Coden and Dr. Joseph Garner, provides a new technological approach to understanding the origins of stereotypies, which are repetitive, seemingly goal-less behaviors common in captive animals and a hallmark of certain human disorders. By focusing on the biochemical state of the mice, the researchers were able to pinpoint a set of proteins in the blood that are associated with the severity of these behaviors. While the study establishes a strong correlation, the authors caution that more research is needed to determine whether oxidative stress is a cause of these behaviors and if antioxidant treatments could be effective.
A Closer Look at Oxidative Stress
Oxidative stress is a condition that occurs when there is an excess of reactive oxygen species, or free radicals, in the body’s cells, and not enough antioxidants to neutralize them. This imbalance can lead to cellular damage and is implicated in a variety of diseases. The Stanford research team investigated the link between this “REDOX imbalance” and the stereotypies observed in mice. These behaviors, which can include excessive grooming or circling, have been documented in almost every species of captive mammal and bird. In humans, they are often associated with neurodevelopmental and neuropsychiatric disorders.
The researchers hypothesized that oxidative stress might play a role in the development of these behaviors. To test this, they measured levels of key biomarkers of oxidative stress in the blood of mice and compared them to the severity of their repetitive behaviors. This approach allowed them to move beyond purely genetic or environmental explanations for these behaviors and explore the underlying biochemistry. The study was designed to identify specific molecules that could serve as indicators of this imbalance and its behavioral consequences.
Biomarkers of Repetitive Behavior
The study identified several key biomarkers that were strongly associated with the severity of stereotypies in mice. These findings provide a more precise way to measure the relationship between oxidative stress and repetitive behaviors and could lead to new diagnostic methods. The researchers used a multi-pronged approach, focusing on a well-known antioxidant as well as a broader analysis of proteins in the blood.
Glutathione as a Key Indicator
One of the primary biomarkers investigated was glutathione, a crucial antioxidant that is considered a gold-standard measure of the body’s oxidative state. The researchers found a significant positive correlation between blood glutathione levels and the severity of stereotypies in young mice. This suggests that in younger animals, higher levels of this antioxidant are associated with more intense repetitive behaviors. This finding was particularly interesting because it was age-dependent. The same correlation was not observed in older mice, indicating that other factors may be at play as the animals age.
Advanced Proteomics Reveals a Broader Picture
To gain a more comprehensive understanding, the researchers employed a state-of-the-art proteomics approach to identify a wider range of proteins associated with oxidative stress and repetitive behaviors. This powerful technology allowed them to analyze the entire set of proteins in the blood and identify a “biomarker profile” of REDOX imbalance and stereotypy severity. They found strong relationships between proteins linked to oxidative stress, glutathione levels, and the severity of the behaviors. The consistency of these protein profiles across different strains of mice suggests a robust biological connection.
Age and Developmental Factors
A key finding of the study was the difference in the link between oxidative stress and repetitive behaviors in young versus old mice. The association between glutathione and stereotypy severity was only present in the younger cohort, suggesting that oxidative stress may be particularly influential during early development. This age-specific effect points to a potential developmental vulnerability to REDOX imbalance.
The authors suggest that this imbalance may contribute to the developmental origins of stereotypies, highlighting potential new targets for early detection and intervention. The fact that some of the protein associations were also independent of age suggests that while oxidative stress may be a key factor in the onset of these behaviors, other mechanisms may contribute to their persistence in older animals. This complex interplay between age, genetics, and environment is an important area for future research.
Translational Potential for Human Health
The researchers are optimistic about the potential for their findings to be translated to human clinical populations. Many of the proteins identified in the study are evolutionarily conserved, meaning they are present in both mice and humans. Furthermore, many of these same proteins are also associated with neurodevelopmental and psychiatric conditions in humans that are characterized by repetitive behaviors. This suggests that the biomarker profiles identified in mice could one day help in the development of new diagnostic methods and treatments for disorders such as autism and schizophrenia.
The authors state that their findings “provide numerous clues to follow and a new technological approach to understanding repetitive behaviors.” By identifying specific proteins in the blood that are linked to these behaviors, this research opens the door to the possibility of developing blood tests that could predict the risk of developing abnormal repetitive behaviors. However, they stress that much more research is needed before these findings can be applied in a clinical setting.
Limitations and Future Directions
While the study provides compelling evidence for a link between oxidative stress and repetitive behaviors, the authors are careful to note that their findings are correlational. This means that while they have shown a strong association, they have not proven that oxidative stress causes these behaviors. It is possible that the repetitive behaviors themselves could be causing the oxidative stress, or that another, unknown factor is responsible for both.
The next step for researchers will be to investigate this causal relationship. Studies will be needed to determine if treatments that reduce oxidative stress, such as antioxidant therapies, can prevent or reduce the severity of these behaviors. The researchers also plan to further investigate the age-dependent nature of their findings and to explore the full range of genetic and environmental factors that contribute to these complex behaviors. Despite the unanswered questions, this study provides a significant step forward in our understanding of the biological basis of repetitive behaviors and offers hope for new therapeutic strategies.