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Derealization: new evidence for the role of dopamine


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#1 curiousmind

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Posted 01 February 2020 - 02:06 PM

My experience on this forum has been that there is more knowledge and confidence in understanding depersonalization as opposed to derealization. It also seems to me that many patients and members of this forum find derealization symptoms much more ominous due to the lack of information on the "visual aspect" of the disorder, to use forum-terminology. This is why I am making this post. 

 

I have taken the following information from a relatively recent study (2018) with the title "Neuromolecular basis of faded perception associated with unreality experience" by Yokokawa et al. Please read the paper in its entirety, my interpretation may inevitably be inadequate/flawed[link]. 

 

The study makes the basic claim that derealization symptoms are mediated by dopaminergic activity in the striatum, please see the paper for how they reached this conclusion. Whats more, the study also implies that this piece of information is in line with the fronto-limbic model for depersonalization proposed by Anthony David, and the low dopamine is likely caused by an inhibibotry mechanism in the frontal lobes.

  • "We discovered that the individual differences of dopamine D2 receptor availability in executive striatum were positively associated with activities of the right middle frontal gyrus (BA46), a part of the dorsolateral prefrontal cortex (DLPFC), and the left parietal cortex for the subjective faded condition."
  • "the current finding indicates that individuals with lower endogeneous dopamine synthesis show higher activity in the frontoparietal network for subjective faded perception, and the lower dopamine may invade to build internal models of the predicted world, observed as the unreality feeling in the current study."
  • "Furthermore, over the last two decades, a strong association of frontal and parietal activity and visual awareness has been established. A number of studies have shown that frontoparietal activity is associated with changes in the contents of visual consciousness."

So dopamine is low, but not because of neurodegeneration or toxicity, but because of an inhibitory mechanism that has been proposed and accepted for some years now. 

 

The reference to the previous research is made here:

  • "Previous neuroimaging studies of depersonalization disorder patients observed increased activities in the frontal and parietal cortex, and proposed that the emotional numbing or detachment in these patients was associated with the hyperactive top-down control system that inhibits emotional responses. DLPFC is also associated with the experience of presence in a virtual reality environment, where the higher activity in DLPFC was associated with the lower experience of presence and reality."

 

The study also makes reference to the attentional mechanism which I have in a previous post [link] speculated is central in the disorder. 

  • "Frontal and parietal cortex, where the former is anatomically connected with executive striatum and both are functionally connected with striatum, compose the top-down attentional control system."

 

All in all the study concludes:

  • "Taking together both the observations of the striatal dopaminergic transmission and the proposed frontoparietal system, it could be speculated that the unreality experience based on subjective faded perception is influenced by the interaction between striatal dopaminergic transmission that plays a role in broadcasting the expectation-based sensory information to the cortex and the frontoparietal network, which in turn are necessary for conscious perception of fadedness and for the top-down allocations based on the subjective faded perception induced by the experimental settings of the current study."


#2 curiousmind

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Posted 01 February 2020 - 03:02 PM

The study mentioned in the original post hints at Levodopa (L-DOPA) [link] to maybe ameliorate derealization symptoms. This claim is not made explicitly but rather implied, and no trials of any kind have been conducted with regards to L-DOPA in relation to DPD specifically. Trade names include Sinemet, Pharmacopa, Atamet, Stalevo, Madopar, and Prolopa. 

 

However, there is some anecdotal information, some who have tried L-DOPA have seen an improvement/relief in dissociative symptoms. 

https://www.dpselfhe.../29269-sinemet/



#3 Aridity

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Posted 01 February 2020 - 03:14 PM

Will mucuna pruriens be good enough?



#4 curiousmind

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Posted 01 February 2020 - 03:18 PM

I do not think, and didn't mean to suggest that increasing dopamine through external means will de facto improve your symptoms (though it could in theory, and based on some who use Sinemet). 

 

rTMS treatment to the rVLPC will have the effect of naturally raising the dopamine in the striatum (as mentioned in the original post). 

The frontal lobe is inhibiting limbic structures which have the effect of causing low dopamine. 

 

The point of the post was sort of just to shed light on the ominous and uncanny derealization sensations as many lack an understanding there. Dopamine is low in the striatum, but this is likely because of overactivity in the frontoparietal region. Normalising the frontoparietal region will resolve the dopamine issues, hence the derealization.



#5 zouzoux

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Posted 11 February 2020 - 09:58 AM

I have derealization too, became better in the sense it doesn't feel as fake as before but vision is still different. Over activity in the brain is interesting since I read that tinnitus could also be a result of overactive neurons firing randomly and I had tinnitus and derealization after my panic attack. Now besides rTMS any other means to reduce activity in the brain ? Its been 2 years now and I feel close to recovery and don't have issues functioning day to day but I would not say no for having a better vision. 



#6 curiousmind

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Posted 11 February 2020 - 03:10 PM

I have derealization too, became better in the sense it doesn't feel as fake as before but vision is still different. Over activity in the brain is interesting since I read that tinnitus could also be a result of overactive neurons firing randomly and I had tinnitus and derealization after my panic attack. Now besides rTMS any other means to reduce activity in the brain ? Its been 2 years now and I feel close to recovery and don't have issues functioning day to day but I would not say no for having a better vision. 

Lamotrigine combined with an SSRI has seemed to have worked in some patients (about 55% in this trial). Why does this work? We don't know, because lamtorigine as a monotherapy did not improve symptoms of DPD, and an SSRI alone has not shown to be beneficial in majority of patients. That being said "there is evidence to support the view that glutamate hyperactivity might be relevant to the neurobiology of depersonalization." [link] Considering that lamotrigine acts to inhibit glutamate activity, lamotrigine+SSRI might help at least members of a subgroup of patients, if you don't mind taking a psych med this is definitely something that is worth trying. There is no guarantee that it will work for you, but if you are interested then a psychiatrist will be able to prescribe this to you upon an accurate diagnosis. What the lamotrigine studies found was that when lamotrigine works for the patient, the overactive region in the DPD-brain (the rVLPFC) is shown to reduce in terms of neuronal activity, and the insula increases in terms of neuronal activity, suggesting that things are being normalised [link]. So yes, this combination may be able to help you with both DP and DR aspects theoretically. (On a side note: interestingly lamotrigine has anecdotally helped some patients with visual snow and tinnitus, there are also some very limited but existing studies that showed this.)

 

rTMS is the closest thing as of now when it comes to a "cure" and requires no pharmacological intervention. More on this soon, but there is a lot of hype regarding rTMS research and DPDR, there is currently one being conducted in France. The problem with rTMS is that it is very very expensive and insurance doesn't cover it, especially not for DPD. The other problem is that to get appropriately treated for DPD with rTMS, you need to find an rTMS clinic that knows about DPD, knows about its neurobiological underpinning, understands that this condition needs to be treated at the rVLPFC or TPJ or maybe the angular gyrus, but not at the DLPFC (which is the typical depression protocol). Furthermore, the clinic needs to be able to target the affected region using a special apparatus called neuronavigation. Over the next couple of years, as clinicians/doctors become more aware of the disorder, this type of treatment will become more available, and as research progresses, this treatment will be more effective. Until then lamotrigine+SSRI is worth giving a shot. 

 

You say though that you have made strides to recovery and have only minor symptoms. If this is so, maybe I would wait and push through, full remission may be on its way. It is one thing to say that there are these structural and functional changes in the "depersonalized brain", there is no doubt that this is true, but that is not to say the these structural and functional abnormalities cannot be resolved on its own through time, acceptance and other non-intervention treatments. Anecdotally, many have reported full remission without meds or rTMS, so this is possible too. 



#7 Jackk11

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Posted 08 July 2020 - 10:51 PM

I do not think, and didn't mean to suggest that increasing dopamine through external means will de facto improve your symptoms (though it could in theory, and based on some who use Sinemet).

rTMS treatment to the rVLPC will have the effect of naturally raising the dopamine in the striatum (as mentioned in the original post).
The frontal lobe is inhibiting limbic structures which have the effect of causing low dopamine.

The point of the post was sort of just to shed light on the ominous and uncanny derealization sensations as many lack an understanding there. Dopamine is low in the striatum, but this is likely because of overactivity in the frontoparietal region. Normalising the frontoparietal region will resolve the dopamine issues, hence the derealization.

I think eventually it will be the ventroMEDIAL pfc that will be the target. This area looks more promising however it’s hard to navigate and reach with current standard technology.




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