Oxidative Stress Mechanisms in Mood Disorders

Oxidative stress arises from an imbalance between the generation of reactive oxygen and nitrogen species and the capacity of antioxidant defences. In mood disorders such as major depressive disorder and bipolar disorder, excessive free radicals can damage lipids, proteins and nucleic acids, leading to neuronal dysfunction and loss of synaptic integrity. Mitochondrial dysregulation further amplifies reactive species production and disrupts cellular energy homeostasis, while chronic oxidative insult interacts with inflammatory pathways to drive neuroprogression. This convergence of redox imbalance, neuroinflammation and impaired neuroplasticity compromises key regions involved in mood regulation, including the hippocampus and prefrontal cortex. Alterations in neurotrophic factors, such as reduced brain-derived neurotrophic factor, and dysregulation of the hypothalamic–pituitary–adrenal axis potentiate vulnerability to stress. Recognition of oxidative stress as a central mechanism has prompted exploration of antioxidant strategies—ranging from dietary interventions to small-molecule therapies—and encouraged the identification of peripheral markers for monitoring disease state and treatment response. Collectively, these insights underscore the global significance of redox biology in both the pathophysiology and potential management of mood disorders.

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Oxidative Stress Mechanisms in Mood Disorders publication trend

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Technical terms

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage cellular components.

Antioxidant defences: Enzymatic and non-enzymatic systems that neutralise free radicals and limit oxidative damage.

Lipid peroxidation: Oxidative degradation of lipids leading to cell membrane dysfunction and formation of reactive by-products.

Neuroinflammation: Immune activation within the central nervous system involving cytokines and glial cells.

Neuroplasticity: The ability of neural circuits to adapt structurally and functionally in response to experience or injury.

Mitochondrial dysfunction: Impairment of the organelle responsible for energy production, often accompanied by excess ROS generation.

References

1. A Meta-Analysis of Oxidative Stress Markers in Depression. PLOS ONE (2015).
2. Markers of Oxidative Stress and Neuroprogression in Depression Disorder. Oxidative Medicine and Cellular Longevity (2015).
3. Peripheral Markers of Depression. Journal of Clinical Medicine (2020).
4. Antioxidant and Anti-Inflammatory Effects of Carotenoids in Mood Disorders: An Overview. Antioxidants (2023).
5. Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study. Antioxidants (2022).
6. Oxidative Stress Markers and Antioxidant Enzymes in Children and Adolescents with Depressive Disorder and Impact of Omega-3 Fatty Acids in Randomised Clinical Trial. Antioxidants (2021).