Oxidative Stress in Psychiatric Disorders

Oxidative stress arises when the generation of reactive oxygen species exceeds the capacity of endogenous antioxidant defences, resulting in cellular damage to lipids, proteins and nucleic acids. The brain’s high oxygen consumption, abundant polyunsaturated fatty acids and relatively low antioxidant reserves render it particularly susceptible to redox imbalance. A growing body of evidence indicates that oxidative stress contributes to the pathophysiology of major depressive disorder, bipolar disorder, schizophrenia and substance use disorders through mechanisms that include mitochondrial dysfunction, neuroinflammation and altered neurotransmitter signalling. Biomarkers of oxidative damage—such as lipid peroxidation products and oxidised nucleosides—are elevated in patient samples, while genetic and epigenetic factors modulate individual vulnerability. Understanding these pathways has spurred interest in antioxidant strategies and lifestyle interventions as adjunctive treatments to restore redox homeostasis and ameliorate psychiatric symptoms.

Research from Nature Portfolio

Recent work has demonstrated the utility of machine learning approaches in incorporating oxidative stress biomarkers to improve the detection and severity grading of major depressive disorder. By combining blood‐based measures of antioxidant status and reactive oxygen species with sociodemographic and clinical variables, weighted random forest classifiers achieved area under the curve values exceeding 0.90 for multiclass severity prediction. Feature‐importance analyses consistently highlighted glutathione levels among the top predictors, underscoring its potential role as a peripheral marker to support clinical decision‐making and tailor interventions.

Oxidative Stress in Psychiatric Disorders publication trend

The graph below shows the total number of articles in oxidative stress in psychiatric disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen, including free radicals, that can damage cellular components when abundant.

Oxidative stress: A state in which ROS production overwhelms antioxidant defences, leading to molecular and cellular injury.

Redox homeostasis: The balanced regulation of oxidation–reduction reactions that maintains cellular health and function.

Glutathione (GSH): A tripeptide antioxidant that neutralises ROS and supports detoxification processes.

Hypothalamic–pituitary–adrenal (HPA) axis: A neuroendocrine system that governs stress hormone release and interacts with redox regulation.

Malondialdehyde (MDA): A by‐product of lipid peroxidation used as a marker of oxidative damage to cell membranes.

Single‐nucleotide polymorphism (SNP): A common genetic variation at a single DNA base, which can influence enzyme function and disease susceptibility.

References

1. Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents. Translational Psychiatry (2024).
2. The Disease Model of Addiction: The Impact of Genetic Variability in the Oxidative Stress and Inflammation Pathways on Alcohol Dependance and Comorbid Psychosymptomatology. Antioxidants (2023).
3. Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder. International Journal of Molecular Sciences (2023).
4. Detecting depression severity using weighted random forest and oxidative stress biomarkers. Scientific Reports (2024).