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Is depression the missing link between inflammatory mediators and cancer?

Barbara Polityńska1, Olga Pokorska1, Anna M Wojtukiewicz1

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Cancer patients have higher depression risks, impacting quality of life and survival. Neuroinflammation, through pathways like kynurenine and glutamate, may explain this link, offering new therapeutic targets.

Keywords:
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Area of Science:

  • Neuroscience
  • Oncology
  • Psychiatry

Background:

  • Cancer patients exhibit increased depression rates compared to the general population.
  • This depression is linked to adverse outcomes, including reduced quality of life, poorer prognosis, and increased mortality.
  • Current depression theories, focusing on monoamine neurotransmitter dysfunction, are insufficient to explain depression in cancer patients.

Purpose of the Study:

  • To explore the underlying pathophysiological mechanisms linking cancer and depression.
  • To investigate the role of neuroinflammation in the development of depression among cancer patients.
  • To identify potential therapeutic targets for managing depression in cancer.

Main Methods:

  • Review of existing theories on depression and cancer.
  • Examination of recent advances implicating neuroinflammatory mechanisms.
  • Analysis of proposed pathways: kynurenine pathway, hypothalamic-pituitary-adrenal axis, and glutamatergic pathway.

Main Results:

  • Neuroinflammation, involving peripheral inflammation mirrored centrally, may promote chronic brain inflammation.
  • Three key routes involving proinflammatory mediators are implicated: kynurenine pathway, impaired hypothalamic-pituitary-adrenal axis feedback, and glutamatergic excitotoxicity.
  • Activation of the kynurenine pathway affects serotonin levels and causes neurotoxicity.
  • Proinflammatory mediators disrupt hypothalamic-pituitary-adrenal axis regulation.
  • Glutamate excitotoxicity may contribute to cancer-associated depression.

Conclusions:

  • Neuroinflammation is a likely mechanism underlying depression in cancer patients.
  • Understanding these pathways can inform the development of targeted therapies.
  • Improved therapeutic strategies are needed to enhance the care of cancer patients experiencing depression.