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NY Times: Same Genetic Basis Found in 5 Types of Mental Disorders

Messages
445
Location
Georgia
Hugely important. Think it isn't related to CFS or FM? Think again. Depression is highly related to CFS. A great percentage of people with our illness have a genetic susceptibility.

By GINA KOLATA

Published: February 28, 2013

The psychiatric illnesses seem very different — schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disorder. Yet they share several genetic glitches that can nudge the brain along a path to mental illness, researchers report. Which disease, if any, develops is thought to depend on other genetic or environmental factors.

Their study, published online Wednesday in the Lancet, was based on an examination of genetic data from more than 60,000 people worldwide. Its authors say it is the largest genetic study yet of psychiatric disorders. The findings strengthen an emerging view of mental illness that aims to make diagnoses based on the genetic aberrations underlying diseases instead of on the disease symptoms.

Two of the aberrations discovered in the new study were in genes used in a major signaling system in the brain, giving clues to processes that might go awry and suggestions of how to treat the diseases.

“What we identified here is probably just the tip of an iceberg,” said Dr. Jordan Smoller, lead author of the paper and a professor of psychiatry at Harvard Medical School and Massachusetts General Hospital. “As these studies grow we expect to find additional genes that might overlap.”

The new study does not mean that the genetics of psychiatric disorders are simple. Researchers say there seem to be hundreds of genes involved and the gene variations discovered in the new study confer only a small risk of psychiatric disease.

Steven McCarroll, director of genetics for the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T., said it was significant that the researchers had found common genetic factors that pointed to a specific signaling system.

“It is very important that these were not just random hits on the dartboard of the genome,” said Dr. McCarroll, who was not involved in the new study.

The work began in 2007 when a large group of researchers began investigating genetic data generated by studies in 19 countries and including 33,332 people with psychiatric illnesses and 27,888 people free of the illnesses for comparison.

The researchers studied scans of people’s DNA, looking for variations in any of several million places along the long stretch of genetic material containing three billion DNA letters. The question: Did people with psychiatric illnesses tend to have a distinctive DNA pattern in any of those locations?

Researchers had already seen some clues of overlapping genetic effects in identical twins. One twin might have schizophrenia while the other had bipolar disorder. About six years ago, around the time the new study began, researchers had examined the genes of a few rare families in which psychiatric disorders seemed especially prevalent.

They found a few unusual disruptions of chromosomes that were linked to psychiatric illnesses. But what surprised them was that while one person with the aberration might get one disorder, a relative with the same mutation got a different one.

Jonathan Sebat, chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at the University of California, San Diego, and one of the discoverers of this effect, said that work on these rare genetic aberrations had opened his eyes. “Two different diagnoses can have the same genetic risk factor,” he said.

In fact, the new paper reports, distinguishing psychiatric diseases by their symptoms has long been difficult. Autism, for example, was once called childhood schizophrenia. It was not until the 1970s that autism was distinguished as a separate disorder.

But Dr. Sebat, who did not work on the new study, said that until now it was not clear whether the rare families he and others had studied were an exception or whether they were pointing to a rule about multiple disorders arising from a single genetic glitch.

“No one had systematically looked at the common variations,” in DNA, he said. “We didn’t know if this was particularly true for rare mutations or if it would be true for all genetic risk.” The new study, he said, “shows all genetic risk is of this nature.”

The new study found four DNA regions that conferred a small risk of psychiatric disorders. For two of them, it is not clear what genes are involved or what they do, Dr. Smoller said. The other two, though, involve genes that are part of calcium channels, which are used when neurons send signals in the brain.

“The calcium channel findings suggest that perhaps — and this is a big if — treatments to affect calcium channel functioning might have effects across a range of disorders,” Dr. Smoller said.
There are drugs on the market that block calcium channels — they are used to treat high blood pressure — and researchers had already postulated that they might be useful for bipolar disorder even before the current findings.

One investigator, Dr. Roy Perlis of Massachusetts General Hospital, just completed a small study of a calcium channel blocker in 10 people with bipolar disorder and is about to expand it to a large randomized clinical trial. He also wants to study the drug in people with schizophrenia, in light of the new findings. He cautions, though, that people should not rush out to take a calcium channel blocker on their own.

“We need to be sure it is safe and we need to be sure it works,” Dr. Perlis said.
 
Messages
15,786
Hugely important. Think it isn't related to CFS or FM? Think again. Depression is highly related to CFS. A great percentage of people with our illness have a genetic susceptibility.
I have yet to see a study using appropriate questionnaires or other methods to determine any mood disorders in ME patients. On the other hand, I have read a ton of studies using questionnaires where physical or cognitive limitations can account for giving answers which are interpreted to mean mood disorder is present.

If you know of any studies that back up your statement regarding depression in ME or a genetic susceptibility, rather than equating disability with depression, please share it so that I can be enlightened.
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
and if these illnesses are autoimmune, WHAT PROVOKES THE AUTOIMMUNE RESPONSE, EH?
let me see...
adjunctivants ("Meat's back on the menu, boys!" or rather Andrew Wakefield...)
heavy metals (UK governemnt let chilren be soaked in lead fumes until 2000 even though they knew the danger)
organophosphates (again UK government lies to protect the companies many of them end up working for!)
excess disease spread caused by air travel and confining people especially kids in huge numbers in poorly ventilated buildings

mmmm and we wonder why we have problems?
 

natasa778

Senior Member
Messages
1,774
Interesting. Does 23andMe test for these SNPs? CACNA1 (?)

Anyone tried Nimodipine ?


just copying my post from another thread

Re calcium channelopathy in ME, that is nothing new actually a few researchers have suggested looking into more deeply, there are several published papers including one or two case studies treating post-viral ME with calcium antagonists.

I wrote years ago about various aspects of calcium channel dysufnction in autism (years before postmortem findings + chemokine receptor polymorphism findings confirmed much of my hypotesis :))

If bookies were taking bets on this I would have been rich by now LOL. Still waiting for the science to catch up with a couple more pieces of the oracle so if anyone out there willing to take bets do let me know ;-)


That case study was nimodipine I believe. The docs figured post viral ME was there 'cos of viruses messing up ion channel function ... which is the crux of my theory :) certain polymorphisms, both in ca channel themselves AND in nearby G-protein linked (esp chemokine!!!) receptors will push you over the limit following environmenal / external events
 

beaverfury

beaverfury
Messages
503
Location
West Australia
just copying my post from another thread




That case study was nimodipine I believe. The docs figured post viral ME was there 'cos of viruses messing up ion channel function ... which is the crux of my theory :) certain polymorphisms, both in ca channel themselves AND in nearby G-protein linked (esp chemokine!!!) receptors will push you over the limit following environmenal / external events

Hi Natasa,

What class of drugs antagonize chemokine receptors? I'm not going to pop one, don't worry. Just trying to fill out
my me/cfs knowledge base.

http://autismcalciumchannelopathy.com/
http://autismcalciumchannelopathy.com/Conclusion.html
These links are good. Once again the theories fit the pathologies of me/cfs, as so many other theories do.
I just wish they could jump ahead and fit an effective treatment to me/cfs.

Regards Nimodipine ,I havent been able to find any trials. Anecdotally it sounds promising, but not world beating.
http://livingwithchronicfatiguesyndrome.wordpress.com/2012/11/26/nimodipine-for-me/

Dr. Mason Brown has seen many of his ME/CFS patients improve with Nimodipine usage. He writes, “Nimodipine helps twenty per cent (of ME/CFS patients) very quickly, another twenty per cent over six months, and all others to varying degrees over a period of time.” He improved his own health to 95% with Nimodipine usage as a treatment for his ME/CFS. He states “The work of nimodipine is at least fourfold: to release the backlog of neurotoxins and waste products from the brain, to open up the brain circulation, to allow in oxygen and nutrients to enter and to help cognitions, pineal, hypothalamic, and pituitary function.”
Dr. J. Goldstein, now retired, specialized in the treatment of ME patients in California. He used Nimodipine as a primary treatment for M.E. and has called it “one of the most useful treatments for ME/CFS and Fibromyalgia.” He also writes, “About 40% of CFS/FM patients taking nimodipine experience relaxation, increased energy, a decrease in tender point sensitivity, improved exercise tolerance, and enhanced mental clarity…. Nimodipine has been shown to release dopamine, serotonin, and acetylcholine…. Tolerance does not develop to the vasodiliatory effects of nimodipine, but sometimes does to its amelioration of CFS/FM symptoms.” He recommends taking 30mg to 60mg 3 times a day.
 

natasa778

Senior Member
Messages
1,774
Hi Natasa,

What class of drugs antagonize chemokine receptors? I'm not going to pop one, don't worry. Just trying to fill out
my me/cfs knowledge base.

LOL
there are none, unfortunately. At least there wasn't one couple of years ago when I last looked, apart from ONE super promising brand new drug entering phase II trials when I last looked. Japanese. I have tried searching since but lost the link and drug's name and now can't find it so no idea what is happening to it ... it was a specific CCR antagonist....
 

PhoenixDown

Senior Member
Messages
456
Location
UK
Hugely important. Think it isn't related to CFS or FM? Think again. Depression is highly related to CFS. A great percentage of people with our illness have a genetic susceptibility.
Depression is really a big misnomer and the word shouldn't be used in the context of defining health conditions, it guarantees confusion and therefore worse treatment of patients by doctors & society as a whole. It's been a waste-basket diagnosis since it's inception, this is NOT to say that people with this diagnosis have nothing wrong with them.
 

Jenny

Senior Member
Messages
1,388
Location
Dorset
Interesting. Does 23andMe test for these SNPs? CACNA1 (?)

Anyone tried Nimodipine ?

Yes, I had a brain haemorrhage a few years ago and was put on it for a few months. My ME got quite a lot better but that could just have been chance (it was summer and I'm usually better then). I've tried lower doses since, which didn't help. I might try to persuade a doctor to give me the higher dose again when I've finished the various treatments I'm doing at the moment.

There are lots of threads on this drug.
 
Messages
445
Location
Georgia
Depression is really a big misnomer and the word shouldn't be used in the context of defining health conditions, it guarantees confusion and therefore worse treatment of patients by doctors & society as a whole. It's been a waste-basket diagnosis since it's inception, this is NOT to say that people with this diagnosis have nothing wrong with them.

Not true. They are talking about "Major Depressive Disorder" which shows up very profoundly in brain scans and tests. You might be thinking of minor depression, situational melancholia, "the blues." MDD has organic roots and can be crippling.

Nobody has agreed on what the exact parameters of CFS are; something I think most people can agree on. (Does it include PEM? Or doesn't it?) But in my personal experience, many folks with CFS have parents, relatives with MDD, bipolar, ADD, etc.
 

natasa778

Senior Member
Messages
1,774
Hi Natasa,

What class of drugs antagonize chemokine receptors? I'm not going to pop one, don't worry. Just trying to fill out
my me/cfs knowledge base.

http://autismcalciumchannelopathy.com/
http://autismcalciumchannelopathy.com/Conclusion.html
These links are good. Once again the theories fit the pathologies of me/cfs, as so many other theories do.
I just wish they could jump ahead and fit an effective treatment to me/cfs.

Regards Nimodipine ,I havent been able to find any trials. Anecdotally it sounds promising, but not world beating.
http://livingwithchronicfatiguesyndrome.wordpress.com/2012/11/26/nimodipine-for-me/

Dr. Mason Brown has seen many of his ME/CFS patients improve with Nimodipine usage. He writes, “Nimodipine helps twenty per cent (of ME/CFS patients) very quickly, another twenty per cent over six months, and all others to varying degrees over a period of time.” He improved his own health to 95% with Nimodipine usage as a treatment for his ME/CFS. He states “The work of nimodipine is at least fourfold: to release the backlog of neurotoxins and waste products from the brain, to open up the brain circulation, to allow in oxygen and nutrients to enter and to help cognitions, pineal, hypothalamic, and pituitary function.”
Dr. J. Goldstein, now retired, specialized in the treatment of ME patients in California. He used Nimodipine as a primary treatment for M.E. and has called it “one of the most useful treatments for ME/CFS and Fibromyalgia.” He also writes, “About 40% of CFS/FM patients taking nimodipine experience relaxation, increased energy, a decrease in tender point sensitivity, improved exercise tolerance, and enhanced mental clarity…. Nimodipine has been shown to release dopamine, serotonin, and acetylcholine…. Tolerance does not develop to the vasodiliatory effects of nimodipine, but sometimes does to its amelioration of CFS/FM symptoms.” He recommends taking 30mg to 60mg 3 times a day.

just found this, from 2011


Nat Rev Immunol. 2011 May;11(5):355-63. doi: 10.1038/nri2972. Epub 2011 Apr 15.
Overcoming hurdles in developing successful drugs targeting chemokine receptors.

Chemokines and their receptors are central to the inflammatory process and are attractive therapeutic targets. Drugs that inhibit chemokine receptors are approved for the treatment of HIV infection and for stem cell mobilization, but none have been approved yet for the treatment of inflammatory and/or autoimmune diseases. We analyse the challenges of developing chemokine receptor antagonists, and propose that inappropriate target selection and ineffective dosing, not the 'redundancy' of the chemokine system, are the main barriers to their use as anti-inflammatory therapies. We highlight evidence suggesting that chemokine receptor inhibition will prove to be an effective therapy in inflammatory diseases.



calcium antagonists (nifedipine I believe) were trialled in phase two for HIV - neuroAIDS, results looked promising but don't think it ever went to phase 3 ...
 

PhoenixDown

Senior Member
Messages
456
Location
UK
Not true. They are talking about "Major Depressive Disorder" which shows up very profoundly in brain scans and tests. You might be thinking of minor depression, situational melancholia, "the blues." MDD has organic roots and can be crippling.
That doesn't change the fact that it is commonly used as a waste-basket diagnosis. Also remember those scans are NOT done on the millions diagnosed with major depressive disorder. The fact that it can be crippling doesn't stop it from being a waste basket diagnosis handed out when doctors can't be bothered to investigate or have prejudices against the patient.


Both the CDC definition and the Canadian Consensus definition of CFS include PEM.
The CDC & CCC definitions do not exclude those without PEM, only the ICC criteria does this.
 
Messages
445
Location
Georgia
That case study was nimodipine I believe. The docs figured post viral ME was there 'cos of viruses messing up ion channel function ... which is the crux of my theory :) certain polymorphisms, both in ca channel themselves AND in nearby G-protein linked (esp chemokine!!!) receptors will push you over the limit following environmenal / external events

Natasha,
Your theory sounds good (or the theory you quoted)!
Given what was strongly represented in the results of this huge study, your explanation is now the front-runner, coming down the finish line. But are there several other polymorphisms that overlap, changing our disease process?
 

natasa778

Senior Member
Messages
1,774
Natasha,
Your theory sounds good (or the theory you quoted)!
Given what was strongly represented in the results of this huge study, your explanation is now the front-runner, coming down the finish line. But are there several other polymorphisms that overlap, changing our disease process?

LOL. Yes absolutely (re your question) ... interferon polymorphisms also seem involved, at least in autism. Also serotonin ... I also suspect HERV polymophisms will play a big role, including in ME (already indicated in MS)!
 

August59

Daughters High School Graduation
Messages
1,617
Location
Upstate SC, USA
I saw his interview on TV and he seemed very excited as well for his partners. A lot of what he said was above my head, but I definitely picked up on the calcium-channel blockers. One thing that may be real good to come out of it is that it will possibly supply a diagnostic marker!??!?1

But, he did say that there were family lines that had all of the morphisms(?) and none of them had any of the 5 diseases.
 

natasa778

Senior Member
Messages
1,774
Yes of course, genetic polymorphisms are not causative factors, but point to vulnerability ...