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Summary: A new study shows that oxidative stress (an imbalance between harmful molecules and antioxidants) may contribute to the repetitive behaviors seen in mice, similar to those seen in autism spectrum disorder and schizophrenia. The researchers found that higher levels of oxidative stress biomarkers, including glutathione and specific proteins, were linked to more severe stereotypies in young mice.
These protein profiles were consistent across different strains of mice, suggesting a strong biological connection. The findings reveal new potential biomarkers and therapeutic targets for repetitive behavior disorders, although more research is needed to confirm whether antioxidant treatments could help.
Key facts
REDOX Link: Oxidative stress markers such as glutathione strongly correlate with the severity of repetitive behavior. Age-specific effect: Associations were stronger in young mice, suggesting an early developmental vulnerability. Translational Potential: The identified protein biomarkers could aid early detection and treatment of human disorders involving repetitive behaviors.
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Abnormal repetitive behaviors in mice are strongly linked to multiple biomarkers of oxidative stress, which occurs when antioxidants are unable to counteract the effects of harmful molecules in the body, according to a study published November 5, 2025 in the open access journal PLOS One by Kendall Coden and Dr. Joseph Garner of Stanford University, USA. However, more research is needed to test whether antioxidants can prevent or treat these behaviors.
Stereotypies are abnormal, repetitive, and seemingly goalless behaviors prevalent in the animal kingdom. They have been documented in almost all species of mammals and birds in captivity, including laboratory animals, zoo animals, and farm animals.
Furthermore, they are a central feature of several neuropsychiatric and human neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia. Despite well-documented environmental risk factors associated with stereotypies in captive animals, the developmental origins of these behaviors remain elusive.
Previous research suggests that several neuropsychiatric and neurodevelopmental conditions are related to REDOX imbalance, a state in which the physiological demand for antioxidants exceeds their bioavailability. However, the relationship between REDOX imbalance and stereotyping has not been clear.
To fill this knowledge gap, Coden, Garner and their collaborators investigated whether REDOX imbalance is associated with the severity of stereotypies in mice. The researchers measured blood levels of the antioxidant glutathione, a standard biomarker of REDOX imbalance.
The results showed that glutathione levels were positively associated with the severity of stereotypies in young mice, but not in old mice. Using a state-of-the-art proteomic approach, the researchers identified broader biomarker profiles of REDOX imbalance and severity of stereotypies.
As predicted, they found strong relationships between proteins related to REDOX imbalance and both glutathione levels and stereotype severity. Some of these associations were found only in young mice and others were independent of age, suggesting that other factors contribute to stereotypies in old mice.
These proteomic findings were replicated in a separate validation set of mice, indicating that these profiles are robust and strain-independent.
Together, these data indicate that REDOX imbalance may contribute to the developmental origins of stereotypy, highlighting new targets for early detection and intervention.
Furthermore, the results suggest that plasma glutathione levels or levels of the identified protein biomarkers may serve as risk predictors for developing abnormal repetitive behaviors.
According to the authors, the evolutionarily conserved nature of the proteins they identified suggests that the results have promising translational potential for clinical populations.
However, they caution that the results are correlational in nature, so it is still unclear whether REDOX imbalance is causally related to the development of stereotypes. More research is required on the causal relationship between REDOX imbalance and stereotypy, and its translation to other species such as humans, to confirm the generality of the results.
Additionally, more research is needed to determine whether antioxidant therapies can prevent or treat stereotypies in mice.
The authors add: “Our findings show that REDOX imbalance (greater demand than supply of antioxidants) is related to repetitive behaviors, and that specific proteins found in the blood may provide a clearer and more accurate way to measure this relationship.
“Many of the proteins identified in our study are also associated with psychiatric and neurodevelopmental conditions, suggesting that this set of proteins could help guide the development of new diagnostic methods and treatments for disorders involving repetitive behaviors.”
“The great mystery of repetitive behaviors is that individuals differ greatly in both risk and severity, even when they grow up in the same environment and share the same genetics,” adds Garner, professor of comparative medicine at Stanford Medicine.
“This mystery also gives us hope that repetitive behaviors can be prevented or cured. That’s why this work is such an exciting breakthrough, giving us so many clues to follow and a completely new technological approach to doing so.”
Funding: This project was supported by a Stanford Medicine Discovery Innovation Award awarded to Dr. Joseph P. Garner. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Key questions answered:
A: Abnormal repetitive behaviors in mice were strongly associated with biomarkers of oxidative stress, suggesting a link between REDOX imbalance and the development of these behaviors.
A: REDOX imbalance occurs when the body’s antioxidants cannot neutralize harmful molecules, resulting in oxidative stress that can disrupt brain development and behavior.
A: Many of the identified proteins are conserved across species, meaning the same biomarkers could help predict or treat repetitive behaviors seen in neurodevelopmental disorders such as autism and schizophrenia.
About this research news on ASD and behavioral neuroscience
Author: Hanna Abdallah
Source: More
Contact: Hanna Abdallah – PLOS
Image: Image is credited to Neuroscience News.
Original research: Open access.
“Stereotypy is strongly related to multiple biomarkers of oxidative stress: a possible common etiology for abnormal repetitive behaviors” by Kendall Coden et al. PLUS ONE
Abstract
Stereotypy is strongly related to multiple biomarkers of oxidative stress: a possible common etiology of abnormal repetitive behaviors
Spontaneous stereotypies (abnormal, repetitive, and seemingly goalless behaviors) in captive animals resemble stereotypies documented in patients with neurodevelopmental disorders, including evidence of homologous corticostriatal dysfunction and shared behavioral abnormalities.
Although environmental risk factors for stereotypies are well documented, their developmental pathophysiology remains unclear. However, as previously discovered for compulsive behavior, there is increasing evidence that REDOX imbalance may be related to stereotypy.
To examine the nature of this relationship, we first tested whether plasma glutathione level, the standard biomarker of REDOX imbalance, predicts the severity of stereotypy in N = 19 C57BL/6 mice.
After confirming the presence of this relationship, we used a proteomic approach (Olink) to identify a broader profile of biomarkers of dysfunction.
We found that the expression of 9 proteins correlates with the plasma glutathione level and the expression of 15 proteins correlates with the severity of stereotypy. A subset of these proteins was also correlated with stereotype severity in a validation cohort of CD1 mice (N = 28).
To further support the role of REDOX imbalance in the developmental pathophysiology of stereotypies, the identified proteins were associated with REDOX physiology, dopamine physiology, and human neurodevelopmental disorders presenting stereotypies.
These data suggest that REDOX imbalance may contribute to the developmental pathophysiology of abnormal repetitive behaviors and highlight promising new targets for intervention.
