THEORY - PAS AND BRAIN DAMAGE

flynn

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Feb 28, 2018
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Another theory of how PAS arises relates to brain damage. It's thought that Accutane has caused some kind of brain damage which has altered the functioning of the brain, this has resulted in changes to brain blood flow/metabolism or simply resulted in the death/destruction of brain cells/neurons, which helps to explain the persisting nature of the mental side effects of PAS.

This theory is based upon studies which have linked Accutane to brain damage and brain changes. Here I will list some of the evidence in favour of the brain damage theory and then follow with my own opinion on these matters and how relevant they are to PAS.

1. Many symptoms of traumatic brain injury (TBI) are similar/same as symptoms of PAS - such as "TBI is associated with increased incidences of seizures, sleep disorders, neurodegenerative diseases, neuroendocrine dysregulation, and psychiatric diseases, as well as non-neurological disorders such as sexual dysfunction, bladder and bowel incontinence, and systemic metabolic dysregulation that may arise and/or persist for months to years post-injury." - https://www.ncbi.nlm.nih.gov/m/pubmed/20504161/

2. Accutane was shown to alter brain fuctioning in acne patients. A 4-month treatment trial with isotretinoin was associated with a decrease in brain functioning in the orbito-frontal cortex (-21% change versus 2% change with antibiotic), this is a brain region implicated in depression - http://www.ncbi.nlm.nih.gov/pubmed/15863802

3. Accutane was shown to suppress hippocampal neurogenesis in mice, showing that clinical doses of Accutane may result in hippocampal cell loss - http://www.ncbi.nlm.nih.gov/pubmed/15251924

4. Accutane decreases hypothalamic cell numbers in vitro and may contribute to depression related behaviours in mice - https://www.ncbi.nlm.nih.gov/pubmed/20708044


My Thoughts

Firstly, though its interesting to note that many of the symptoms of PAS are similar to the symptoms of traumatic brain injury, this still doesn't mean much. There are many symptoms of TBI which are not seen in PAS such as seizures, blurry vision, disorientation and confusion. Additionally, bladder/bowel incontinence is not necessarily the same thing as irritable bowel syndrome/IBS (which some users develop). I also implore you to look at the symptoms of Post Finasteride Syndrome (PFS), in my opinion these symptoms more accurately mirror the symptoms of PAS than TBI - http://www.pfsfoundation.org/post-finasteride-syndrome-overview/

Secondly, when studies look at changes in brain metabolism/activity/blood flow and they find changes. Is this really surprising? We already know that there are persistent changes to the activity of our own neural pathways, thats why we don't feel the same or have the same desires/responses to hormones etc. as pre-accutane. I don't need a brain scan to tell me that my dopaminergic reward system isn't working as correctly as it should be. The question is why is this the case? and what is more likely? Either a drug which has been prescribed to millions of people is capable of literally destroying/rendering broken whole brain circuits OR the activators of these brain circuits aren't present or functioning correctly. Just because there is a reduced blood flow/metabolism in an area of the brain it doesn't imply that part of the brain is permanently damaged, it could just imply there is less activity in that region due to less neural stimulation. Which factors in the brain do you think alter brain metabolism/activity/blood flow? Surely the activity of major neurotransmitter pathways by things such as Dopamine play a pretty significant role in determining the metabolism/activity/blood flow of a particular brain region. I mean ultimately this is the core function of the brain.

My point is, if you were able to bring some of this neural activity back online, I expect you would also see an increase in blood flow/metabolism/activity in these brain regions once again. Just to reinstate this, Dopamine for example is a vasodilator. The activity of pathways such as the dopaminergic pathways (which I highly suspect is involved in PAS) will likely effect blood flow to regions of the brain. The Orbitofrontal cortex receives dopaminergic signals and so dopamine activity is likely to effect the activity of this brain region. Essentially, there may be altered blood flow on scans. But if you were able to reactivate the right pathways, we may see a recovery of some of that blood flow/activity. Here is an article which talks about dopamine as a vasodilator - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2044648/

Another point to make for the sexual dysfunction symptoms: People have reported experiencing recovery or partial recovery of sexual function (libido etc.) for brief or long periods. I spoke to a guy on a Facebook Accutane group who said he experienced a week of feeling almost nothing for his wife i.e. zero libido etc. whilst on Accutane however this eventually subsided and he is now back to normal. If the sexual dysfunction side effect was caused by permanent brain damage, how could anyone ever experience any significant improvement in these symptoms. Surely if the pathway has been damaged/destroyed, it will no longer work. This makes no sense in light of permanent brain damage.

Finally I'll grant you that Accutane damages the hippocampus whilst you are on it. But this still doesn't explain sexual dysfunction and this doesn't mean that neurogenesis (and the damage) in the hippocampus can't necessarily be recovered overtime by substance/supplements which stimulate hippocampal neurogenesis. Also these studies rarely look at whether these changes have persisted beyond stopping treatment.

Things to Consider

I will continue to add to this post
 
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