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Depression, Inflammation and Pain…The Clinical Link to Success

Article presented by Labrix Clinical Services, LLC

In clinical practice we routinely work with patients who are depressed, and also suffering from
inflammation frequently coupled with life altering pain. While an individual patient may present with a
single concern, exploration of their overall chemistry often reveals multiple co­morbid variables.

Depression and inflammation are strongly correlated, as demonstrated by a 2013 peer­reviewed
report. The clinical findings of this report revealed significantly higher inflammatory index scores (a
composite score including the inflammatory markers tumor necrosis factor­α (TNF­α), interleukin­6 (IL­
6), interleukin­10 (IL­10), and C­reactive protein (CRP)) in individuals with major depressive disorder
(MDD) who attempt or complete suicide when compared to both controls and patients with MDD and
lower suicidal ideation.

Often thought of as affecting cognition and mood, depressive symptoms may manifest somatically as
pain in some individuals and, as with suicidal ideation, may be linked to inflammation. A 2013 study
examining participants with metabolic syndrome correlated the increased leptin levels seen in
metabolic syndrome with somatic depressive symptoms but not total or cognitive depressive
symptoms. The conclusion that leptin is independently associated with somatic depressive symptoms
in patients with metabolic syndrome suggests that depression can hurt, independent of the patient’s
state of mind.

As practitioners, we can address the inter­relationship among depression, inflammation and pain not
only with our typical hormonal, dietary and lifestyle interventions but also with neurotransmitter
assessment and support. Often thought of as the main mood­regulating neurotransmitter, serotonin
support may be key for many patients in this population. Pro­inflammatory cytokines including IL­6 and
IL­10, among others, acutely stimulate central serotonin neurotransmission. Of particular note here is
interferon gamma (IFN­γ) and its relationship with serotonin. IFN­ γ reduces serotonin production by
stimulating the enzyme indoleamine 2,3­dioxygenase (IDO), which converts tryptophan into
kynurenine. Overstimulation of IDO leads to depletion of tryptophan and, therefore, to reduced
synthesis of serotonin.

In what other ways can supporting neurotransmitter balance benefit our patients with depression,
inflammation and pain? How do neurotransmitter imbalances beyond serotonin affect these patients?

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2. Miller AH, Ancoli­Israel S, Bower JE, et al. Neuroendocrine­immune mechanisms of behavioural
comorbidities in patients with cancer. J Clinical Oncol 2008; 26:971­982. Provides an excellent
overview of the factors leading to depression in patients treated for cancer.
3. Levandovski R, Pfaffenseller B, Carissimi A, Gama CS, Hidalgo MP. The effect of sunlight exposure
on interleukin­6 levels in depressive and non­depressive subjects. BMC Psychiatry. 2013 Mar
4. O’Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O’Farrelly C, Malone KM.
Suicidal ideation is associated with elevated inflammation in patients with major depressive
disorder. Depress Anxiety. 2013 March 15.
5. Chirinos DA, Goldberg R, Gellman M, Mendez AJ, Gutt M, McCalla JR, Llabre MM, Schneiderman
N. Leptin and its Association with Somatic Depressive Symptoms in Patients with the Metabolic
Syndrome. Ann Behav Med. 2013 Feb 23.

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