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<p>Depression is a widespread and debilitating mental disorder characterized by complex neurobiological changes that go beyond simple neurotransmitter imbalances. New evidence emphasizes the critical role of inflammation and oxidative stress in the development of depression. Chronic low-grade inflammation and the overproduction of reactive oxygen and nitrogen species interfere with vital neurobiological functions, including neurotransmitter regulation, mitochondrial activity, synaptic plasticity, and neurogenesis. Additionally, inflammation and oxidative stress form a cycle that perpetuates itself, worsening neuronal damage and leading to brain structural changes often seen in people with depression. This narrative review thoroughly examines the neurobiological roots of depression, focusing on how inflammatory and oxidative pathways interact. It discusses how pro-inflammatory cytokines and oxidative damage disrupt neuroplasticity and neurotransmission, especially through the NFĸB and Nrf2 signaling pathways. The review also considers the therapeutic potential of anti-inflammatory drugs, antioxidants, Nrf2 activators, and lifestyle changes as supplementary or alternative treatments for depression. Furthermore, it highlights the importance of personalized medicine approaches based on inflammatory and oxidative biomarkers. Gaining a deeper understanding of the complex relationship between inflammation, oxidative stress, and depression opens new possibilities for more effective, targeted treatments, ultimately improving outcomes for those affected by this intricate disorder.</p>

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The interplay between inflammation and oxidative stress in depression: pathogenic mechanisms and treatment approaches

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Omkar Kumar Kuwar,
  • Mamta Sachdeva Dhingra,
  • Ayushi Maloo,
  • Tejinder Singh,
  • Inderjeet Singh,
  • Lavish Kumar,
  • Mayank Attri

摘要

Depression is a widespread and debilitating mental disorder characterized by complex neurobiological changes that go beyond simple neurotransmitter imbalances. New evidence emphasizes the critical role of inflammation and oxidative stress in the development of depression. Chronic low-grade inflammation and the overproduction of reactive oxygen and nitrogen species interfere with vital neurobiological functions, including neurotransmitter regulation, mitochondrial activity, synaptic plasticity, and neurogenesis. Additionally, inflammation and oxidative stress form a cycle that perpetuates itself, worsening neuronal damage and leading to brain structural changes often seen in people with depression. This narrative review thoroughly examines the neurobiological roots of depression, focusing on how inflammatory and oxidative pathways interact. It discusses how pro-inflammatory cytokines and oxidative damage disrupt neuroplasticity and neurotransmission, especially through the NFĸB and Nrf2 signaling pathways. The review also considers the therapeutic potential of anti-inflammatory drugs, antioxidants, Nrf2 activators, and lifestyle changes as supplementary or alternative treatments for depression. Furthermore, it highlights the importance of personalized medicine approaches based on inflammatory and oxidative biomarkers. Gaining a deeper understanding of the complex relationship between inflammation, oxidative stress, and depression opens new possibilities for more effective, targeted treatments, ultimately improving outcomes for those affected by this intricate disorder.