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Brain damage as a cause of HPPD: the loss of specific GABA-releasing inhibitory interneurons


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In this thread, I will try to pinpoint the cause of HPPD based on what current studies are suggesting. For years, I've felt the need and desire to find a solid hypothesis on the cause of HPPD. I felt very uncomfortable not having an exact idea about the cause of HPPD, which for me, was necessary to have hope for future treatments.

I hope one day, we as a community will have a consensus on the cause of HPPD so that there is a scientific foundation to start with. How much better would it be, that to a new user, instead of having to say "We have no idea what causes HPPD", we're able to say: "You probably have damaged some specific neurons in your brain which are now causing your symptoms". That should be more relieving and also makes it easier for the user to put into perspective that this disorder is not the end of the world.

 

I have found two quotes from HPPD studies that suggest brain damage is a cause of HPPD:

"It has been proposed that symptoms of HPPD are caused by damage to inhibitory interneurons expressing 5-HT2A serotonin receptors to which most hallucinogens bind. This loss of cortical inhibition (21, 22) may manifest in aberrant occipital delta oscillations (23–25) associated with visual hallucinations." [source]

"The available evidence suggests that HPPD symptoms may be a result from a misbalance of inhibitory-excitatory activity in low-level visual processing and GABA-releasing inhibitory interneurons may be involved." [source]

With "damage", I suspect they mean the death of GABA-releasing neurons through overstimulation of 5-HT2A receptors. This damage may extend to other brain areas, and cognitive or psychiatric symptoms may be involved. The reason that the damage doesn't resolve on its own is that neuronal loss is tenacious and creates a non-permissive environment near the site of injury, preventing proper healing which results in persistent functional defects.

 

This thread is a work in progress. I will try to post updates when I have time to read more studies.

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In the short future, I would say no. For now, we can treat our symptoms with anticonsulvants/benzodiazepines or other compounds that modulate excitatory/inhibitory activity. What I've seen around is some people have success with Lamotrigine, Clonidine, Clonazepam, and recently someone mentioned Perampanel which looks pretty interesting.

However, the research area about brain injury is rapidly evolving with a lot of potential medicines coming into clinical trials that specifically focus on reversing brain injury. Although currently, they are mostly in trial for conditions like Alzheimers, Parkinsons, Multiple Sclerosis etc. It is reasonably to be hopeful that, say within ten years, we will have medicine that can improve or even reverse brain injuries. In any way, don't get scared about the idea that brain injury is permanent because it simply is not. At least not with modern technologies. In mice and animals it has already been reversed many times.

 

I have found more clues that HPPD is likely a brain injury, from the Wikipedia page:

"Chronic disinhibition may occur from destruction and/or dysfunction of cortical serotonergic inhibitory interneurons involving the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA)". [source]

And the Wikipedia page about Depersonalization-derealization disorder also suggests abnormalities that indicate injury or neuronal loss of some kind:

"Several studies analyzing brain MRI findings from DPDR patients found decreased cortical thickness in the right middle temporal gyrus, reduction in grey matter volume in the right caudate, thalamus, and occipital gyri, as well as lower white matter integrity in the left temporal and right temporoparietal regions." [source]

If you have DP/DR from HPPD, then likely you could also have some kind of neuronal injury in other areas of the brain (so not only visual cortex), which unfortunately as I just realize seems pretty extensive. Perhaps there is loss of more inhibitory interneurons across the whole brain which would indicate more widespread injury not only concentrated to a small part of the brain.  I will try to read some more about this.

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23 hours ago, MentholFlavoring said:

 

Dans un futur proche, je dirais non. Pour l'instant, nous pouvons traiter nos symptômes avec des anticonvulvants/benzodiazépines ou d'autres composés qui modulent l'activité excitatrice/inhibitrice.  Ce que j'ai vu, c'est que certaines personnes ont du succès avec  la lamotrigine, la clonidine, le clonazépam, et récemment quelqu'un a mentionné le perampanel qui semble assez intéressant.

Cependant, le domaine de la recherche sur les lésions cérébrales évolue rapidement avec de nombreux médicaments potentiels entrant dans des essais cliniques qui se concentrent spécifiquement sur l'inversion des lésions cérébrales. Bien qu'actuellement, ils soient principalement à l'essai pour des maladies telles que la maladie d'Alzheimer, la maladie de Parkinson, la sclérose en plaques, etc., il est raisonnable d'espérer que, disons d'ici dix ans, nous disposerons de médicaments capables d'améliorer ou même d'inverser les lésions cérébrales. De toute façon, n'ayez pas peur de l'idée qu'une lésion cérébrale est permanente parce qu'elle  ne l'est tout simplement pas . Du moins pas avec les technologies modernes. Chez les souris et les animaux, il a déjà été inversé plusieurs fois.

 

J'ai trouvé plus d'indices que HPPD est probablement une lésion cérébrale, à partir de la page Wikipedia :

"La désinhibition chronique peut se produire à partir de la destruction et / ou du dysfonctionnement des interneurones inhibiteurs sérotoninergiques corticaux impliquant le neurotransmetteur inhibiteur, l'acide gamma-aminobutyrique (GABA)". [la source]

Et la page Wikipédia sur  le trouble de dépersonnalisation-déréalisation suggère également des anomalies qui indiquent une blessure ou une perte neuronale quelconque :

"Plusieurs études analysant les résultats de l'IRM cérébrale de patients atteints de DPDR ont révélé une diminution de l'épaisseur corticale dans le gyrus temporal moyen droit, une réduction du volume de matière grise dans le caudé droit, le thalamus et le gyri occipital, ainsi qu'une intégrité inférieure de la substance blanche dans les temporaux gauche et droit. régions temporo-pariétales. [la source]

Si vous souffrez de DP / DR de HPPD, vous pourriez également avoir une sorte de lésion neuronale dans d'autres zones du cerveau (donc pas seulement le cortex visuel), ce qui, malheureusement, comme je viens de le réaliser, semble assez étendu. Peut-être y a-t-il une perte d'interneurones plus inhibiteurs dans tout le cerveau, ce qui indiquerait une lésion plus étendue non seulement concentrée sur une petite partie du cerveau. Je vais essayer de lire un peu plus à ce sujet.

Hello do you think that deep brain stimulation with the implant that is placed on the brain could attenuate or eliminate the Hppd?

Deep-Brain-Stimulation-DBS.jpg

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Thank you for mentioning this, it looks interesting. However, it involves a very invasive and dangerous surgery with many complications and is very unlikely to be applied unless someone is so severely disabled that even basic activities become impossible and other options have been exhausted. Sometimes, it's done to Parkinson's Disease patients and seems to improve their symptoms significantly. It does look like it could potentially help with HPPD.

There are frequent discussions on this forum about non-invasive brain stimulation like TMS, that could be an option. It's mentioned in some of the studies as a potential option, I believe some people have tried it here, but I don't know how successful it has been.

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On 5/24/2022 at 10:34 PM, MentholFlavoring said:

 

Thank you for mentioning this, it looks interesting. However, it involves a very invasive and dangerous surgery with many complications and is very unlikely to be applied unless someone is so severely disabled that even basic activities become impossible and other options have been exhausted. Sometimes, it's done to Parkinson's Disease patients and seems to improve their symptoms significantly. It does look like it could potentially help with HPPD.

There are frequent discussions on this forum about non-invasive brain stimulation like TMS, that could be an option. It's mentioned in some of the studies as a potential option, I believe some people have tried it here, but I don't know how successful it has been.

so whats your thoughts about the neuroimaging study that will be happening? Do you think it will show the part of the brain affected? 

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