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Mayer-Gross

Member Since 31 Dec 2010
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Topics I've Started

Angular Gyrus trail still not finished

08 February 2021 - 08:18 PM

One I know, had yesterday been in contact with the French researcher behind the rTMS trail at the right angular gyrus. The trail should according to the design from 2015 be a placebo controlled with a 100.patients. Last year they hoped to be finish around sept 2020 but they are still open for patients living in France. 

 

This is really depressing that a trail can take more than 6.years because they can not locate a 100.patients in the Paris area. Research into depersonalization was until recently done at two small units in London and New York that made some small examinations like brain scans and small trail,- clearly underfunded if one looks at the sizes of the patients used. Now, these are closed. 

 

So, the only research there is are some small studies done in other european countries. This is not enough if there shall be some hope of a treatment. 

 

The unawareness and that it is still highly undiagnosed seems to be the core problem in getting founding, recutting patients for doing more research into this condition. Deeply concerning. 


New brain scan study in depersonalization.

22 January 2021 - 07:34 PM

I have overlooked this brain scan study of 6.patients from Switzerland with some germans co authors from 2020. Until 2013-15 there was two small research units doing research into depersonalization. One in New York and one at King´s College in London. These were very poorly staffed with around 4-5.people working permanently there and some ph.d students and external researchers from other places coming there for a specific study. The studies were all very small in size likely due to the lack of funding as depersonalization is so mis and under-diagnosed until recently. So, almost every publication coming out had relation to these to units for nearly two decades. Now, they are closed. The positive side of it is that there are coming studies from other countries. One angular gyrus trial in France, one scan in Japan, two structural MRI/DTI scans in Germany and now this small study from Switzerland. So, there is increased awareness about the disorder in other countries and that is positive.

 

Brain scans of depersonalization is closely related to rTMS as a potential treatment. If a location, network can be found to be over or underachieve it could in theory be stimulated with rTMS and the state would normalize. Both former research units tried to find such locations and do some very small trials at them with the rTMS technology available back then. That excluded many locations as they were to deep for stimulation with conventional rTMS back then.

 

The study from Switzerland brings  challenges to locations also the models previously used. The former model thought of a model with a overactive prefrontal cortex that suppressed the limbic system (area for emotions) This overactivity should make a state of numbing/having no emotions, detachment, unreality. With rTMS is was thought the inhibition of such a overactive area would take depersonalization away.

 

The German studies put this model in to question. They also said the the size of the studies previously done was very small. Below a minimum of 20.patients. They agreed though that rTMS would likely be the intervention.

 

This study was done with a scanner called ALS-MRI that is similar to a fMRI but uses the iron in the blood of the brain as a tracer for brain metabolism.

 

They found a significant under activity in the left orbitofrontal cortex that is involved in sensory integration in pre-psychotics with DP/DR symptoms. They think that it this under-activity or failure of this area to make a integration of sensory input that makes some part of the disorder. The emotional numbing do not come from emotional supression but a failure to integrate them.

 

They also found a overactivity in the very dopamine rich area in the brain called the left Caudate nucleus that is a location deep in the brain that is also very affected in states like obsessive compulsive disorder. So, an element of having OCD like symptoms in depersonalization is likely related to this.  

This can likely be changes with the type of rTMS equipment used in research.

The study is very small as all previously studies done but it puts a major challenge to the models previously used in depersonalization. It can be read here. It is very small but points towards the need for more newer and larger brain scans done.

 

.https://www.frontier...020.535652/full

 

There was a review of the brain studies done to date in depersonalization last year and they pointed towards the conflicts about locations, networks that have only become worse with this study. They recommended to do a study were a combination of advanced rTMS with rMRI was used. So, a location coming up as over or underachieve was stimulated to some sessions in 10-15.patients to see if there was any reductions in symptoms and then scan them again and see if some of the brain had normalized or changed.An area could also be ruled out as having any relevance.  It could also be that some locations works in 50% and not in the rest and people with depersonalization in reality have some differences in their emotional regulation done by the brain-

 

There is a need for a research unit that can work with this continuously with many patients. The germans wrote they had difficulties finding sufficient number of patients, The French angular gyrus trail have been under way for 6.years likely also due to the lack of patients in a Paris area. The Swiss study wrote that they difficulties finding people with "pure" depersonalization (many have is secondary to another disorder and can not be used). Many with "pure" depersonalization they contacted in Switzerland declined to take one hour out for a brain sca.  So, a research unit can likely only be in the London area or New York/Boston as many likely there have been seen by the former research units and many local psychiatrists are aware of the disorder.A research unit shall be in an area with 300-500.people with "pure depersonalization" who will be a part of research  For legal reason a research unit can only take nationals of the authorities that have approved the research.   


Development of more advanced rTMS equipment.

08 December 2020 - 05:09 PM

So, some of you might know that i am very interested in rTMS. It is an intervention the former “Depersonalization research unit” had high hopes for and a German DTI brain imaging study from 2019 also point towards rTMS as the intervention in the disorder. 

 

rtms was developed 25.years ago but only approved to treatment for depression in Europe and the US around 2007. The technology has been very limited to two locations in the brain called the left and right DLPFC. These are very easy to find and stimulate as they are on the surface on the prefrontal cortex. 
 

Around 50% with depression respond to stimulation at these locations. RTMS clinics will often in their material claim a response rate of 70%. But, the reality is that significant number sees a reduction of only 20% of their symptoms- that is very close to placebo. Because these clinics runs a business they will take those who “feels a little better” as respondent. They run a business and it is easy to sell a product by saying it works in 70% and not 50%.

 

That rTMS only works in 50% with depression is one reason why most psychiatrists have been very skeptical of the intervention. In Denmark and in Europe it is offered as a eksperimental treatment at limited numbers of hospitals for depression. 
 

The reason why only 50% with depression respond is related to current technology used in rTMS. In many with depression (and also in depersonalization) the cognitive regulation of emotions is not done in the left or right DLPFC but other locations and networks in the prefrontal cortex. In depression the two other locations are the dorsomedial prefrontal and the right orbito frontal cortex. If you try these locations with a deep coil in depressed at a research facility the response rate for depression is closer to 90%. The reason why it is not a 100% is likely partly because the emotional regulation is done to deep in the brain for a deep coil used today to stimulate. 

 

The problems is that rTMS as it is approved and used today uses coil that can only stimulate 1.cm into the brain. So, it can not treat at deep locations and networks. This is a problem in depersonalization as the over regulation of emotions making a state of numbing is too deep in the brain. This goes for the right VLPFC that can only be partly stimulated with a normal coil-like 30%. Other locations found active in depersonalization and under suspicion like the anterior cingulate/dorsomedial prefrontal cortex and the ventromedial prefrontal is to deep in the brain to stimulate with a normal rTMS. So, one can say that with the current rTMS technology used depersonalization will have a very low response rate due to the areas in the brain where the regulation likely is done. Magventure makes a deep coil that is only used for research that might reasch these areas. But, has just been approved in the US for treatment of obsessive compulsive disorder. It might also be approved in Europe.

 

I read an interview with a danish professor in psychiatry who I have talked to and written when he was chairman of the danish psychiatrists association around 2004. My complaint back then was that they where not aware of the existence of depersonalization disorder. But, in a recent interview he addresses that 15-20% of people might have a depression in their lifetime and of 20% of those no medication will work. They will end up on social programs ect as they are resident to current treatments. He pointed towards rTMS as a treatment and a research program he was a part of for the development of more advanced rTMS equipment.

 

it is as I can see from the danish innovation fund site who have given 2.mio euros to the project and money from two companies will also go into it . It is a danish-German program divided into two sections. 
 

The danish producer of rTMS equipment, Magventure will with researchers from danish technical university( engineers) and a danish center for magnetic resonance and a research center in psychiatry develop a new coil, likely for a deeper and more selective stimulation in the brain that currently can not be stimulated. 

 

The German part of the project is the neuronavigation company “Localite” who shall develop more advanced software for more individual brain stimulation. It looks like they try to develop a navigation system that is not dependent on a MRI scan of individuals. University in Munich is also in the program.

It is a very broad and vague description they come with and I think it is for the protection of the project. We will know more when it a patented.

 

But, the ambitions is to develop rTMS equipment that can be used in refractory depression, other psychiatric conditions and to reduce neurological symptoms in neurological disorders. So, rTMS might end up being much more commonly used in the future if the project succeeds. 

 

 So, they are developing coils for more deeper stimulation and likely equipment that is more precise and easy to use. The program should run until 2023. They will likely start testing some of it in the coming years. So, equipment that can make a deeper stimulation and treat more conditions is under development. The project in danish is here.Try a autotranslate. 
 

https://innovationsf...tent-depression

 

english version of the project: https://www.drcmr.dk...tant-depression


Did you have seperation anxiety as a child?

22 November 2020 - 06:28 PM

With seperation anxiety it could be anxiety for being away from you parents, sleeping at places without your parents ect. I had seperation anxiety as a child and there are some research pointing towards the risk of developing panic anxiety is 3.times higher if one had separation anxiety as a child. Panic anxiety has been seen as a component in development  depersonalization. 

 

 


Lecture by Ruth Lanitus on dissociative subtype of PTSD

13 August 2020 - 04:20 PM

It has been very limited with the research into depersonalization disorder since the depersonalization research unit stopped in 2015. But, there has been a lot of research in PTSD and the dissociative subtype that features of depersonalization and derealization. Among people with PTSD it is estimated that 15% of the have the dissociative subtype. There are some significant overlapping between the dissociative subtype of PTSD and depersonalization disorder. They both share symptoms of emotional numbing, detachment, derealisation. So, it is assumed that the emotional regulation done by the brain is likely the same. So, findings in the dissociative subtype of PTSD can also be used in depersonalization. The leading researcher into the dissociative subtype of PTSD is the Canadian prof in psychiatry, Ruth Lanitus. Here is lecture with her from 2019 based in recent brain scans in PTSD and its dissociative subtype. The recording in not so good as it is recorded from distance but it can be seen. Her point is the dissociation comes from overregulation of emotion done by the ventromedial prefrontal cortex- emotions are suppressed. An area deep in the midbrain called the “periaqueductal gray”/PAG is in the ventral part active in the dissociative state, - all the time. It is a old structure in the brain we share with reptiles. A structure millions of years old.

In normal PTSD the periaqueductal gray is active in the dorsal part, -all the time. They are in a constant state of alert/fight and flight mode. Their emotions are under regulated as the ventromedial prefrontal cortex is underactive- opposite to the dissociative subtype. They can have emotional outburst, have range due to  this under regulation. Their constant state of alert does they have difficulty to find rest and be relaxed.

The dissociative state is a immobilization response that the brain have chosen because a fight and flight response could not be taken. Danger was perceived as being to close. Symptoms like out of body, derealisation is likely connected to the activation of the periaqueductal gray. Emotional numbing is likely result of the overactivity/emotional regulation done by the ventromedial prefrontal cortex. 
 

So, she have recent data from brain scan that shows the involvement of the periaqueductal gray. This is not found in other studies in depersonalization. They likely could scan that area until recently. She points towards ventromedial prefrontal cortex as central in this regulation. The ventromedial prefrontal cortex -both left and right have also been found overactive in studies in depersonalization. It is a location very difficult to manipulate with until recently, as it is to deep to stimulate with rTMS. There have been development of new coils that can likely affect it. But, it is not used by rTMS providers yet. 
 

her lecture is here. 
https://www.youtube....5uW5y4c8&t=270s