On "Here Comes The Sun"
Increasingly evidence is mounting that mood disorders, including, but not limited to the DSM-V diagnosis of "treatment resistant major depressive disorder" (one of the most significant risk factors in predicting suicide attempts, a number of which, sadly, will succeed) and the the immune system.
Pro-inflammatory cytokines are implicated in the pathogenesis of depression by activation of the tryptophan- and serotonin-degrading enzyme indolamine-2,3-dioxygenase (IDO) (Kiank et al. 2010) and by up-regulating serotonin transporter activity (Zhu et al. 2006), leading to reduced availability of serotonin.
Increasingly, Pro-inflammatory cytokines are already being deployed as tools in:
- the therapy of depressive disorder
- use as biomarkers, both predictive of and successful in aiding the differential diagnosis of mood disorders
- targets for cytokine inhibitors and modifiers of cytokine signalling (Lichtblau et al. 2013).
It has been demonstrated that anomolies in the allostatic dynamics of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors p55 and p75 are increased in acutely depressed patients (Himmerich et al. 2008) and TNF-alpha was increased in depressed compared to healthy females (Kahl et al. 2006).
In animals, induction of depressive behaviour can be achieved by administration of TNF- alpha and subsequently reversed by anti-TNF-alpha antibody (Kaster et al. 2012).
In humans, treatment for psoriasis with the anti-TNF-alpha agent etanercept, a TNF-alpha receptor p75-Fc fusion protein, was found to have antidepressant effect (Tyring et al. 2006).
(As an amusing aside: Some researchers in the field were recently heard to informally "comment", during a lunch break at a scientific meeting, of potentially overlooked "diagnostic skillsets" amongst the marketers of an over the counter psoriasis treatment which references "the heartbreak of psoriasis.")
In an animal model of depression, treatment with etanercept reduced depression-like behaviour (Krügel et al. 2013). In bipolar depression (BD), TNF-alpha -levels are considered as potential trait markers for the disorder, and modulation of TNF-alpha may be a target for antidepressant treatment (Soczynska et al. 2009).
As a reminder not to focus on amusing asides: the horrific toll inflicted on sufferers, families, and societies alike by severe, treatment resistant, stubbornly intractable mood disorders cannot be downplayed. In the end, there is absolutely nothing amusing about this.
All the more reason to remember what to focus on: the often thankless task of discovering the enormous, and still largely untapped potential of developing feasible methods of preventing the devastating effects of pro-inflammatory cytokines in the Central Nervous System (CNS), not just for the category of major mood disorders discussed above, but for an ever increasing range of Neurodegenerative/Neurotraumatic/Neuropsychiatric conditions such as Alzheimer's disease, chronic pain syndromes and Traumatic Brain Injury (TBI) sequelae to but a few; is largely being undertaken in spite of "big pharma" not by them:
© Gerald Hecht, 2016. Unauthorized use and/or duplication of this material without express and written permission from this author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Gerald Hecht with appropriate and specific direction to the original content.