Gerald Hecht in beBee in English, Scientists and Research, Medical Researchers Toxicology and Behavioral Neuropharmacology Expert Witness Sep 13, 2016 · 1 min read · 2.7K

On "Here Comes The Sun"

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.

Claire L Cardwell Nov 30, 2018 · #47

@Gerald Hecht After my 'Abilify' experience OD and Withdrawal (doesn't seem right that you go through withdrawal after OD - makes sense biologically, but it's NOT FAIR!), I am blown away by the $700K lawsuit etc.etc. that is being won in the USA.

Behind the Elephant Curtain here in Africa, you really have to SEARCH for this info on Google. You have to type in Abilify OD and the truth comes out on page 3... Even our Doctors don't know and they use the UK Pharmacoepia as a guidance manual. According to SA law there is no point suing as we don't hand out awards here for surviving something. You are lucky to get costs (court costs only).

Claire L Cardwell Nov 30, 2018 · #46

#44 When I look at Donald Trump and his fragrant wife Melania - I do wonder - which half has she had to 'settle' for. The top half or the bottom half?

Melissa Hefferman Jan 13, 2017 · #45

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Gerald Hecht Jan 12, 2017 · #44

#43 @Melissa Hefferman I think they have to be an interaction; FWIW, I think that @Ian Weinberg 'S explanations are the closest view is Spinozian, or Fechnarian --pantheistic, two sides of a coin thing ("what is a quarter; a picture of George Washington or an eagle?")'s choice of "destructive stimuli" worthy of intense attention...getting captured by them..."the little demons" which have captured one's attention so completely that they block out anything else...can most definitely lead to Neurodegenerative sequelae...but it can work the other way too...if the process has gone so far that a person is "unreachable" ...this technique can reverse the damage...the person can be reached and can learn new patterns of adapting to existential realities that we are unable to the old "Pizza Hut" TV spot with Donald Trump and his ex-wife Ivana...where he tells her she can only have half...and then laughs...
...we can't change the fact that that video exists; but we can learn to find the poetry and beauty in it (but not until the "physical plant" [the brain] is physically fit) that point you can watch that video and laugh at our cosmic situation!

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Melissa Hefferman Jan 12, 2017 · #43

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Gerald Hecht Jan 11, 2017 · #42

#41 @Lisa Vanderburg You are most welcome; the best thing right now is to spread the word about the specifics of (not just any "biologic") of etanercept, introduced into the CSF; and the millions of lives it can benefit:

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Lisa Vanderburg Jan 11, 2017 · #41

Well said @Gerald Hecht! Those in the field of research and innovation that give so very many years of disciplined, painstaking graft - in spite of Big Pharma especially - these are the true warriors for our tomorrow. It is their untold sacrifice, often in lonely isolation, fighting a sea of academic bitchery, hat-in-hand to beg for every scrap of funding (which eats more time away from their project); these are our heros!
I know suicide. I know degenerative disease. I know profound depression. What you said about the untold horrific toll of severe mood disorders; I understand. I think so many suffering with life-long profound depression 'hide' its severity because they know what there is currently on offer, and it doesn't work. For their families, they too live in the shadow of this unknown entity, waiting for something to break. It rarely breaks for the good, so bravo to those who selflessly give so much for altruistic reasons and receive so very little in return. Thank you, thank you!!

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Mark Anthony Nov 8, 2016 · #40

"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)" I have witnessed the pain and misery caused by BP ,lesser degree cyclothymia and Psoriasis. Is there money to be made from this research? The reason I ask because there was that Dr who thought Baclofen could assist with the treatment of Alcohol dependency. However , it isn't licenced for the treatment of alcohol dependency in the UK. Apparently, it is such a cheap drug it wouldn't be worth any companies time jumping through the necessary hoops to get it licenced. Not saying I believe​ in it, just saying. Anything that contributes towards helping in this area would be great.

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