Inflammation is a normal part of the body’s defense to injury or infection. However, inflammation is damaging when it occurs in healthy tissues or lasts too long (months or years).
Causes of chronic inflammation include (Inflammation, n.d.):
- environmental chemicals
- poor nutrition and nutritional deficiencies
- imbalanced microbiome (dysbiosis)
- sleep issues
- personal environment
Additional sources of Inflammation (Berk et al., 2013):
• consuming the Standard American diet
• environmental toxins
• low grade infections
• sedentary lifestyle
Inflammation and mental health
Inflammation plays a mediating role in both the risk and progression of depression (Berk et al., 2013).
Depression is a symptom of inflammation. Symptoms include (Greenblatt, 2018) :
- decreased concentration
- decreased appetite
- decreased interest in pleasurable things
Cytokines and Depression
Depressed patients have been found to have (Huang & Lee, 2007):
- higher levels of pro-inflammatory cytokines (TNF- α & CRP) than healthy patients
- lower levels of anti-inflammatory cytokines than healthy patients
Pro-inflammatory cytokines are responsible for activating indoleamine 2,3-dioxygenase (IDO), a tryptophan and serotonin-degrading enzyme (Müller & Schwarz, 2007). Increased levels of IDO, and increased consumption of tryptophan and serotonin, results in a reduction in serotonergic neurotransmission (Müller & Schwarz, 2007) (Greenblatt, 2018).
Inflammation and bipolar disorder
- Bipolar depression and manic episodes may be accompanied by increased pro-inflammatory signalling and T-cell immune activity (Anderson & Maes, 2015)
- Reduced of the protective brain-derived neurotrophic factor (BDNF) is common in bipolar disorder patients. Reduced BDNF is associated with increased inflammatory signaling (Goldstein et al., 2011).
- Lithium is beneficial for treating bipolar symptoms, in part due to its anti-inflammatory actions (Anderson & Maes, 2015).
Sleep loss and inflammation
- In a 12-day study a moderate reduction in sleep duration was associated with a significantly increased amount of inflammatory compounds (Vgontzas et al., 2004).
Trauma and inflammation (Danese et al., 2009):
- immune function is affected in a pro-inflammatory way by childhood maltreatment, abuse, social isolation, and economic hardship.
- people who had stress in childhood are twice as likely to suffer chronic inflammation.
Inflammation and suicide
- In psychiatric patients increased inflammation is associated with increased suicidal ideation (Greenblatt, 2018).
- Patients with depression and high suicidal idealation have been shown to have significantly higher markers of inflammation including TNF-α, IL-6, and C-reactive protein (O’Donovan et al., 2013).
IDO, cytokines (inflammation mediators), and neurotransmission
- Pro-inflammatory cytokines (cell-signalling molecules) increase the activity of Indoleamine 2,3-dioxygenase (IDO) – an important enzyme in tryptophan metabolism.
- IDO degrades tryptophan to kynurenine thereby decreasing amounts of tryptophan available for production of serotonin, and melatonin (important for mood and sleep).
- the kynurenine metabolite quinolinic acid increases excitatory glutamate neurotransmission.
- higher concentrations of kynurenine and a higher kynurenine to tryptophan ratio have been found in overweight and obese versus normal weight people. Obesity is associated with an increased inflammatory state in the body (Fellendorf et al., 2021).
Tryptophan, kynurenine metabolites, and bipolar disorder
- Blood and cerebral spinal fluid concentrations of kynurenine and its metabolites, as well as the kynurenine to tryptophan ratio have been found to be higher in subjects with bipolar disorder versus healthy controls subjects (Anderson & Maes, 2015; Trepci et al., 2021).
- tryptophan degredation by IDO, as driven by a pro-inflammatory state, was found to be more active in bipolar disorder (Fellendorf et al., 2021).
Anderson, G., & Maes, M. (2015). Bipolar Disorder: Role of Immune-Inflammatory Cytokines, Oxidative and Nitrosative Stress and Tryptophan Catabolites. Current Psychiatry Reports, 17(2), 8. https://doi.org/10.1007/s11920-014-0541-1
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Danese, A., Moffitt, T. E., Harrington, H., Milne, B. J., Polanczyk, G., Pariante, C. M., Poulton, R., & Caspi, A. (2009). Adverse childhood experiences and adult risk factors for age-related disease: Depression, inflammation, and clustering of metabolic risk markers. Archives of Pediatrics & Adolescent Medicine, 163(12), 1135–1143. https://doi.org/10.1001/archpediatrics.2009.214
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Goldstein, B. I., Collinger, K. A., Lotrich, F., Marsland, A. L., Gill, M.-K., Axelson, D. A., & Birmaher, B. (2011). Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 21(5), 479–484. https://doi.org/10.1089/cap.2011.0009
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