View Full Version : The up side of finding the genes.


Amtram
03-14-13, 08:19 PM
This is the story of Lilly Grossman (http://phenomena.nationalgeographic.com/2013/03/11/we-gained-hope-the-story-of-lilly-grossmans-genome/), and how a rare genetic defect that affected her dopamine processing and caused shaking and convulsions was discovered to be the cause of her problems. And how understanding the role a medication played in addressing not dopamine, but the specific gene that was broken in her, gave her what's expected to be a normal lifespan.

Because they could find the gene, know what it did (from other human gene studies) and know how a medication interacted with the genome, scientists and doctors were able to diagnose her, and treat her symptoms successfully. Because her condition is a genetic abnormality, and it is so rare, there is no reason to suspect a cause or prevention. But since it was detectable with genome sequencing, she didn't have to suffer with her symptoms for the rest of her life.

While a condition that has multiple genes involved is not going to be so straightforward when it comes to finding causation or making diagnosis, these advances with monogenic conditions put us a step closer each time they're detected and isolated.

That's why genetics is important.

SB_UK
03-15-13, 04:39 AM
Better example (in terms of numbers of people whose lives will be improved).

http://rphr.endojournals.org/cgi/content/full/59/1/409#SEC3
Recently, we reported the dramatic and beneficial effects of daily subcutaneous injections of leptin for reducing body weight and fat mass in three congenitally leptin-deficient children (Farooqi et al., 2002). We have commenced therapy in two other children and seen comparably beneficial results But monogenic disorders are classical genetic - polygenic disorders are epigenetic.

It's the most fundamental of differences which prevents us from extrapolating the monogenic disorder onto the common disorder.

-*-

Amtram
03-15-13, 11:51 AM
And what if the research ends up helping tens of thousands of children later on because it finds additional genetic links, or other genetic markers that respond to the same chemicals?

I would also suggest that you pose your question, "Was the treatment more about building a career for a Western researcher than helping the sick and diseased ?" to, say Lilly Grossman, whose blog is linked in the article. Or you could ask the Beery family directly on their blog (http://dystonia.thebeerys.com/).

The research on this one condition provided information that will also contribute to the understanding of other idiopathic diseases, glutaric aciduria, mitochondrial diseases, cerebral palsy, Parkinson's disease, other dystonias, Tay-sachs and other GM2 gangliosidoses, and dyskinesias worsened by stress. (http://www.ncbi.nlm.nih.gov/pubmed/22782511)

So we already have a pool of about 10 million people worldwide with Parkinson's and more than 750,000 who have cerebral palsy alone. There is no dearth of people who could benefit from research into the genes that contribute to these disorders. Being able to discover the effects of individual genes within a more complex genetic disorder will improve the understanding and treatment of multiple conditions that include mutations of those individual genes.

Fuzzy12
03-15-13, 12:01 PM
is there a downside to finding the genes?? :eek:

I guess, with all medical conditions (and anything really) it always helps to understand as much as possible about it. With more knowledge, we can find better ways of treatment.

Better example (in terms of numbers of people whose lives will be improved).

http://rphr.endojournals.org/cgi/content/full/59/1/409#SEC3
But monogenic disorders are classical genetic - polygenic disorders are epigenetic.

It's the most fundamental of differences which prevents us from extrapolating the monogenic disorder onto the common disorder.

-*-



I think, doubt and skepticism are a good thing but I don't think that's really a fair question. Yes, currently, it might just help a handful of people but at least it is helping some people. As Amtram said, who knows if in the future it might help more people. Also maybe others will build up on this research and find ways to apply the findings to other more prevalent problems.

Also, I believe that research, even just for the sake of research is never wasted. Yes, of course we need to keep in mind that resources and funding are limited and that sometimes priorities have to be taken into account but you never know what useless research of today will result in countless benefits in the future. Every large invention starts small. It has to start somewhere and with some research it is not always clear how it might be applied in a worthwhile way. However, I believe that knowledge is very rarely wasted. It's always a start, a stepping stone to more knowledge.

SB_UK
03-15-13, 12:52 PM
Parkinson's disease

- can be prevented by changing our collective environment.

http://epicureande-lite.blogspot.co.uk/2011/04/following-monastery-diet.html
They apparently do not suffer from heart disease, Parkinson's or Alzheimer's, and the only cancer recorded there is the rare case of prostate cancer.

We can prevent pretty much all disease - and ensure healthy ageing simultaneously.

All environmental (through changing societal infrastructure).

SB_UK
03-15-13, 12:56 PM
is there a downside to finding the genes?? :eek:


No small list of genes accounting for the disease - will be found in the diseases which most people fall victim to.

However - we know how to prevent these diseases from occurring in the first place.

Now - imagine we shatter a piece of glass - I think it's fairly clear that none of us 'd try to put it back together again.

I'm not convinced that the body is any simpler to put back together again once it's broken ... ... however *prevention* of ALL disease is more than possible - given a slight change in societal infrastructure.

Maybe it is possible to restore function - but why not go with what we know can be done - and prevent disease from occurring in the first place ?

The medical degree need only contain information on how to apply the epidemiological method; and as every epidemiologist knows - as soon as disease is eradicated - they're redundant - may put their feet up on a beach someplace and live the rest of their lives knowing they've actually done something worthwhile -
unlike the geneticist.

SB_UK
03-15-13, 01:04 PM
However, I believe that knowledge is very rarely wasted. It's always a start, a stepping stone to more knowledge.


Imagine if I were to record to the micron - the height of every blade of grass in my garden on an attosecond by attosecond basis.

That's useless data.

And isn't distinguishable from the majority of data coming out from genetics.

Data generation in genetics is just (plain and simple) easy.

And there is an infinite (literally infinite amount of data) which may be generated in that field.

Lunacie
03-15-13, 02:21 PM
Imagine if I were to record to the micron - the height of every blade of grass in my garden on an attosecond by attosecond basis.

That's useless data.

And isn't distinguishable from the majority of data coming out from genetics.

Data generation in genetics is just (plain and simple) easy.

And there is an infinite (literally infinite amount of data) which may be generated in that field.

I had to look that up ... attosecond. That would be a bit extreme. However
by comparing the rates of growth of grass in the shade vs grass in the sun,
and other factors, who knows what might be discovered?

Amtram
03-15-13, 02:22 PM
You seem to be operating under the assumption that one thing precludes the other; that investigating science is done at the sacrifice of providing for human needs and vice-versa.

On the other hand, I can think of a fair number of enterprises that confer little benefit to society that could be cut back - not even eliminated - and provide more than enough money, material, and manpower to do both.

We would be able to investigate diet from an evolutionary standpoint, as well. There are historical and current examples of genetic enzyme processing disorders that are a result of regional food availability prior to population mobility.

We would also be able to consider that we have historic evidence of indigenous societies that ate only food that they caught and grew themselves, and practiced egalitarian versions of societal living, and yet still succumbed to communicable disease.

It is genetic and historical data that point to the idea that diet does not, by itself, confer immunity to pathogens or eliminate genetic defects or prenatal deformities. (And one single physically isolated colony of all men will not provide any usable data regarding that. The fact that the monks of Mount Athos, or anywhere else, have not given birth to any children with genetic defects proves nothing about the preventive potential of their lifestyles.)

Dizfriz
03-15-13, 02:26 PM
All knowledge is useful, we just do not always know how or when. Anything that gives us a better understanding of the world in which we live is valuable.

Dizfriz

Conman
03-15-13, 04:55 PM
interesting about medications that work on a gene vs symptoms (as in just helping those without helping the underlying problem), cuz it is true. why bother treating symptoms when you can work on the thing responsible? although it is more than likely difficult to find the troublesome gene(s) for a particular genetic disorder, it's still a study worth going further with

i wonder when i do eventually have the money to blow on getting my genome mapped (or getting my genes sequenced, forget the term but they tell you basically all the genes giving what expressions, %-chance risks for things, etc.), i wonder if at that time theyre gonna have possible genes correlated to AD/HD on that list.

but then again i dont think i want to know all my genes cuz it's not a perfect system, and i dont want the possibility of insurance companies or profession ******* me over if they have access.

Amtram
03-15-13, 07:33 PM
The genetic testing that's available to consumers isn't a full map of the genome. It looks at certain segments that are already associated with common outcomes or origins, but it's not a full sequence.

The insurance conundrum is something that worries a lot of people who hope for a genetic marker - it's a good thing for treatment (or for validating that something actually exists) but it wouldn't take much for it to be turned around and used for denial of treatment. We're a ways away from that, though.

Tyler Durden
03-15-13, 11:54 PM
However we know how to prevent these diseases from occurring in the first place.

Now - imagine we shatter a piece of glass - I think it's fairly clear that none of us 'd try to put it back together again.

I'm not convinced that the body is any simpler to put back together again once it's broken

Maybe it is possible to restore function - but why not go with what we know can be done - and prevent disease from occurring in the first place ?


Excellent analogy, and quite apt, although the neurons in the human brain are far more complex in many regards than pieces of glass.

It also highlights differences in perspective:

Option 1: (this thread) What is there?
Describing those tiny pieces of shattered glass and the original sheet ,finding out you cannot determine causation only rough correlation between the makeup of the glass and the pattern of shattered glass.

Option 2: Why is it there?
Understanding why it broke, what circumstances lead to the glass breaking in the first place, how could you reverse the process and prevent it occuring again.

The glass maker who determines or understands why the glass broke and fixes the problem will less likely break more glass than the glass maker who spends their time analyzing the shattered glass and what the glass was made of.

Not to say these are 2 mutually exclusive approaches, they should be complimentary as both approaches have different perspectives and strengths, in some cases with lower complexity and lower degrees of heterogeneity option one may be the preferable focus but for higher complexity/heterogeneity (disorders such as adhd) option 2 should be the prefered focus.

Lunacie
03-16-13, 10:11 AM
No small list of genes accounting for the disease - will be found in the diseases which most people fall victim to.

However - we know how to prevent these diseases from occurring in the first place.

Now - imagine we shatter a piece of glass - I think it's fairly clear that none of us 'd try to put it back together again.

I'm not convinced that the body is any simpler to put back together again once it's broken ... ... however *prevention* of ALL disease is more than possible - given a slight change in societal infrastructure.

Maybe it is possible to restore function - but why not go with what we know can be done - and prevent disease from occurring in the first place ?

The medical degree need only contain information on how to apply the epidemiological method; and as every epidemiologist knows - as soon as disease is eradicated - they're redundant - may put their feet up on a beach someplace and live the rest of their lives knowing they've actually done something worthwhile -
unlike the geneticist.

But . . . ADHD is not a disease. It's a disorder.

A disease is caused by external factors (virus, bacteria).
A disorder is caused by internal abnormalities.

Just because science is learning how to cure or prevent diseases
doesn't mean that it's known how to cure or prevent disorders.

Tyler Durden
03-16-13, 10:42 AM
But . . . ADHD is not a disease. It's a disorder.

A disease is caused by external factors (virus, bacteria).
A disorder is caused by internal abnormalities.

Just because science is learning how to cure or prevent diseases
doesn't mean that it's known how to cure or prevent disorders.

This is incorrect, both originate externally and both manifest internally.

You can draw many parallels between the two, you could even argue the distinction between the two is mere semantics and that the terms are interchangeable.

Lunacie
03-16-13, 11:44 AM
This is incorrect, both originate externally and both manifest internally.

You can draw many parallels between the two, you could even argue the distinction between the two is mere semantics and that the terms are interchangeable.

You could argue that. I would not.

The "medical model" on which understanding and treatment of ADHD is
based differentiates between internally-caused disorders and externally-
caused diseases.

That medical model says that ADHD is caused by mutations in multiple
genes, and may be coupled with environmental triggers.

So, it might be accurate to say that ADHD as a disorder does both, while a
disorder that is linked to just one genetic mutation originates only internally.

Amtram
03-16-13, 12:15 PM
A disease is caused by pathogens. Communicable disease pathogens are organisms that enter the body from outside.

Genetic conditions are not diseases. Sometimes an article directed to the general population will refer to a "genetic disease," but that doesn't mean that's how it's known in the scientific or medical communities.

Genetic conditions, because they may come along with certain physical vulnerabilities, can result in susceptibility to disease. These diseases can be caused by pathogens, or triggered by factors such as diet and exercise or exposure to chemical triggers. For example, people with the obviously genetic condition of Down's Syndrome are also commonly found to have heart defects that lead to early death.

The genetic predispositions that are being found for heart disease, certain cancers, diabetes, and age-related physical and mental degenerative conditions are sometimes delayed by lifestyle changes or worsened by poor habits, but there's little absolute correlation between genes and destiny or lifestyle changes and prevention.

However, through genetic exploration, we learn important information about the function of genes in building the human body, which helps us know where to look for both good and bad predispositions. Look at the value of finding the genetic origins of viral resistance in the research on AIDS. Look at the value of finding the genes for enzyme processing disorders that allow thousands and thousands of people to live, because they can be treated with medication and specialized diet.

I simply don't understand the value in saying "this area of study didn't tell us exactly what we wanted to hear, so we should abandon all study in this area entirely." This is like saying "Piano is a hard instrument to learn. We should just stop making pianos and writing music for them."

TygerSan
03-16-13, 12:16 PM
My understanding is that a disease is something that has a known cause or set of causes, whereas a disorder or syndrome is defined by is a set of symptoms.

Amtram
03-16-13, 12:26 PM
Harriet Hall has an interesting article on "causes of disease." (http://www.csicop.org/si/show/one_true_cause_of_all_disease/) I believe it takes into account what you said, Tyger San, and definitely expresses it better than I did.

Tyler Durden
03-16-13, 12:36 PM
Lunacie said disorder and disease.

What I meant is that in some cases the 2 terms could be used interchangeably and that.in those cases the differences are merely semantic.

As tygersan said, the difference is one of understanding, disease has a deeper etiological or physiological understanding than disorder.

Internal/external is a blurred line anyway , most of the cells in our body would be considered not "us" or foreign, we are effectively symbiots both internally and externally.

Genetics are a path dependant environmental expression.

Disease and disorder must be initiated externally.

You cannot create something inside that is not a response to something outside, this includes disease, disorder, and on a greater time scale genetics.

Amtram
03-16-13, 12:45 PM
Genetics are not an "environmental expression." And this thread is about genetic conditions and the value of finding their origins in the genome. Perhaps if you wish to discuss a different topic, you should find an appropriate thread or start a new one.

Tyler Durden
03-16-13, 01:00 PM
Amtram by environmental expression I was referring to genetics as the results of responses to interactions with historical environments, the basis for natural selection.

Genetics did not evolve in isolation.

Tyler Durden
03-16-13, 01:19 PM
Sure it would be nice Amtram, but it would be nice to be able to fly around like a bird too, it just isn't that likely.

They have been trying for years to find a genetic causation for adhd, sure there would be value IF specific genetic origin could be found, but it never will be, making this thread a moot point.

SB_UK
03-16-13, 01:54 PM
Sure it would be nice Amtram, but it would be nice to be able to fly around like a bird too, it just isn't that likely.

They have been trying for years to find a genetic causation for adhd, sure there would be value IF specific genetic origin could be found, but it never will be, making this thread a moot point.

- is the point in a nutshell.

It was worth looking - initially.

But - Insanity: doing the same thing over and over again and expecting different results.

Amtram
03-16-13, 02:08 PM
Amtram by environmental expression I was referring to genetics as the results of responses to interactions with historical environments, the basis for natural selection.

Genetics did not evolve in isolation.

So you make up your own terms for things and it's other people's responsibility to figure out what you mean? That's not terribly realistic. Nobody who is talking about evolution or genetics is going to refer to change by natural selection as "environmental expression."

And again, the fact that we haven't found something specific yet is not a valid reason to give up on something which, thus far (and as shown in the OP) has provided a great deal of useful information that has helped many people, and will be used to improve our knowledge in the future.

How far would we have come as a species if our operating philosophy was to give up on anything that didn't work the first time we tried it? We certainly wouldn't be here discussing it on the internet. In fact, most of us wouldn't be here at all.

Lunacie
03-16-13, 02:48 PM
Sure it would be nice Amtram, but it would be nice to be able to fly around like a bird too, it just isn't that likely.

They have been trying for years to find a genetic causation for adhd, sure there would be value IF specific genetic origin could be found, but it never will be, making this thread a moot point.

How can you be so certain that a genetic origin can never be found?

Geonome mapping is still very new, compared to other branches of science,
and yet they ARE finding the answers to some complicated disorders.

Tyler Durden
03-17-13, 03:30 PM
How has genetic research over say the past 20 years helped those with adhd?

Obviously nothing is certain but the odds of finding anything but an obvious 'link' are negligible at best.

As has already been stated, adhd is not a monogenic disorder, and there is no direct genetic relationship.

Further, the same genetics can develop very different behaviours and appearances.

Tyler Durden
03-17-13, 03:47 PM
This may seem slightly tangential but maybe will help illustrate my point.

If you tickle the hind legs of a locust they turn from a solitary to an extremely social creature capable of creating massive swarms, they have exactly the same genetics, environmental stimuli increase seratonin levels and totally change their behaviour( and in this case even physical appearance, a change that is reversible...)

Metamorphosis of the mind...

APSJ
03-17-13, 09:24 PM
While a condition that has multiple genes involved is not going to be so straightforward when it comes to finding causation or making diagnosis, these advances with monogenic conditions put us a step closer each time they're detected and isolated.

That's why genetics is important.

I know next to nothing about genetics, but find what I've read fascinating. I've always imagined that genetic research into ADHD might yield answers to a number of practical questions, given that treatment still remains trial and error in many respects. For example, why do some medications work better than others in different people? Why do some people have some clusters of symptoms but not others? Why are some with ADHD more prone to certain co-morbids? etc.

Is it plausible that these could be, in part, consequences of different groups of ADHD-related genes in different people?

Tyler Durden
03-18-13, 07:19 AM
Genetics are fascinating true, but with regard to adhd the research has produced no real progress in understanding etiological physiological or otherwise with regard to adhd and for good reasons.

If you look at my last post it illustrates how the SAME genetics can produce very different results dependent on ENVIRONMENT.

This is a complexity that belies research on genetics isolated of environmental factors.

For genetic research to produce benefits for adhd and related disorders it must be based on epigenetics, the influence of environment on genetic expression.

This is a big part of why genetic research can NEVER find the solution, it is only looking for a temporary partial symptomatic solution using half of one side of the equation, a quest that would go on forever and could have disastrous unforeseen consequences, profiting pharmaceutical companies but not humanity. It is selling glue for bits of shattered glass instead of reversing the process that created the broken glass in the first place, it will never be a "cure", but there is no profit in cure, and there lies the corrupted motive.

Dizfriz
03-18-13, 07:42 AM
I know next to nothing about genetics, but find what I've read fascinating. I've always imagined that genetic research into ADHD might yield answers to a number of practical questions, given that treatment still remains trial and error in many respects. For example, why do some medications work better than others in different people? Why do some people have some clusters of symptoms but not others? Why are some with ADHD more prone to certain co-morbids? etc.

Is it plausible that these could be, in part, consequences of different groups of ADHD-related genes in different people?


That seems to be the general consensus right now. As an example, due to genetics, some cases of ADHD are more related to reuptake issues and others with production of neurotransmitters. In the first case, Methylphenidate might be the be the better medication to start with as it works more as a reuptake inhibitor and an Amphetamine based med such as Adderol might be better in the second as it tends to enhance production of dopamine.


This is why Barkley thinks that in not too many years, we will be able to do a gene map and recommend medication based on this.

The genetic situation with ADHD in general is, I suspect, similar but much more complex and we will not be able to get a good handle on this for a number of years. I an reasonably confident though that we will get there,

A truly fascinating subject.

Dizfriz

Tyler Durden
03-18-13, 09:42 AM
Exactly, it is not coincidence that those supportive of this approach are those who are proponents of the medicated lifestyle...

mildadhd
03-18-13, 12:03 PM
I would love to learn more about epigenetics.

Because I am not a professional,

and am a Bothist.

I am not exposed to the division in different sectors of science.

I think epigenetics brings many different disciplines together.

That were formally apart.


I have been learning about the societies-economic reality,

and the "battle" between limited funds for research,

but I don't have any first hand experience with such scientific barriers.


I have been unable to discuss genetics,

and learn how all the fascinating things work.

Because of the barriers division.

Without sounding like I am supporting one side or the other.

(because in reality they work together)


I really want to learn everything about genetics.

I think learning about genetics is mandatory.

I want to know how RNA from the center of the cell, (inside the nucleolus)

interacts with the environment, and lots of other things.

Amtram
03-18-13, 12:34 PM
I'm glad that this post got some replies today, because it gives me the opportunity to share this video that I ran across this morning. Here's the description:

BBC Knowledge and Learning is exploring a wide variety of topics from social history to science in a series of three-minute online Explainer documentaries, and commissioned Territory Studio to produce an animated film on the subject of DNA.
As Will Samuel, lead designer and animator on the project explains, the approach taken wasn’t just to look into a scientific future. “We needed to find a graphic style to communicate the beauty and intricacy of DNA. We wanted to create nostalgia; taking the audience back to the days of textbook diagrams and old science documentaries, such as Carl Sagan's COSMOS and IBM’s POWER OF TEN (1977). Using the double helix circular theme as a core design we focused on form, movement and colour to create a consistent flow to the animation, drawing on references from nature, illustrating how DNA is the core to everything around us.”

Three minutes is a short time to explore a subject where most doctorates only scratch the surface, so writer Andrew S. Walsh teamed up with molecular biologist Dr Matthew Adams to distil the script down to the most fundamental elements required to understand not only DNA’s form and function but how our understanding of these discoveries has affected the wider world. While this length may feel restrictive, the team found that this limitation acted as a lens, focusing the piece on the essentials.
The Explainer series is designed to intrigue and inform, encouraging those who discover the documentaries to further explore through links to additional information found on the BBC website.

BBC Knowledge Explainer DNA (http://vimeo.com/60747882)

Amtram
03-18-13, 12:41 PM
Epigenetics is of secondary importance to genetics in some ways. It is a process that happens with every life form that encompasses all the ways that DNA is used to transform a couple of cells into a living being. It doesn't happen unless there's DNA in the first place, and most of what it does is follow the exact instructions of the DNA.

There are a lot of books and videos and articles that cover this in painstaking detail, and they're just really hard to understand if you haven't been introduced to the basics. I'm going to again recommend reading Neil Shubin's "Your Inner Fish," because it explains the process beautifully and in an engaging, conversational style. In addition, Scitable (http://www.nature.com/scitable), Nature Journal's educational site, is filled with all kinds of useful, interesting information that's written in a style geared towards students. If you're not a professional biologist, but you want to know more, it's a great resource.

Tyler Durden
03-18-13, 12:51 PM
Amtram do you have any evidence that genetics are more relevant than epigenetics with regard to 'adhd' being expressed?

Or even better something that can rule out epigenetic factors?

Amtram
03-18-13, 01:48 PM
The evidence is in the way the process inherently works. I really would suggest that you spend some time looking into the various resources that have been provided here that explain genetics and epigenetics, because if you did, you might understand what role each component plays in the development of living creatures.

The amount of information we know - what we've learned in the relatively short period of time since the discovery of DNA - is amazing. How much we've discovered even before sequencing the human genome is awe-inspiring. The process of life is fascinatingly detailed, frustratingly complex, and filled with potential for knowledge and study.

If you limit your thinking to a single aspect of it, you're cheating yourself of some of the most interesting information in the world, IMHO. The fact that you're asking questions like this shows that you've only scratched the surface when it comes to understanding genetics and epigenetics. You're denying yourself the opportunity to discover huge amounts of cool and amazing stuff, and that's a shame.

mildadhd
03-18-13, 01:56 PM
The evidence is in the way the process inherently works. I really would suggest that you spend some time looking into the various resources that have been provided here that explain genetics and epigenetics, because if you did, you might understand what role each component plays in the development of living creatures.

The amount of information we know - what we've learned in the relatively short period of time since the discovery of DNA - is amazing. How much we've discovered even before sequencing the human genome is awe-inspiring. The process of life is fascinatingly detailed, frustratingly complex, and filled with potential for knowledge and study.

If you limit your thinking to a single aspect of it, you're cheating yourself of some of the most interesting information in the world, IMHO. The fact that you're asking questions like this shows that you've only scratched the surface when it comes to understanding genetics and epigenetics. You're denying yourself the opportunity to discover huge amounts of cool and amazing stuff, and that's a shame.


Amtram,

I want to learn all of those things you mentioned.

I learn one step at a time.

And it is hard to express sometimes why I need to know the answer to a question,

before I move on to the next question.


Can DNA "work" without Uracil?

Yes? No? Sometimes?

I need help with this question?

.

Tyler Durden
03-18-13, 02:38 PM
Would you humor us and give a straight answer as opposed to a paragraph of writing who's only purpose is to undermine those who do not agree with you.

Fyi I am not ruling anything out, genetic understanding is prerequisite for epigenetic understanding, it is you who are limiting scope here by ruling out epigenetics...

Epigenetics influence before and after conception, you wish to rule out epigenetic factors all we ask is that you justify this view.

Hope this isn't too much to ask.

mildadhd
03-18-13, 03:03 PM
re·la·tion·ship

1) the state of being related or interrelated <studied the relationship between the variables>


http://www.merriam-webster.com/dictionary/relationship

Dizfriz
03-18-13, 03:25 PM
If you limit your thinking to a single aspect of it, you're cheating yourself of some of the most interesting information in the world, IMHO. The fact that you're asking questions like this shows that you've only scratched the surface when it comes to understanding genetics and epigenetics. You're denying yourself the opportunity to discover huge amounts of cool and amazing stuff, and that's a shame.


Peri, I want to second what Amtram is saying.

You obviously have a good mind and seem to be very inquisitive (my favorite trait).

What I might suggest is instead of focusing on fine detail instead work on getting a good feel for the overall picture on a subject. It is understanding the general picture that allows us to put things into context so as to understand where the data fits in relation to the other pieces of data, to solve the jigsaw puzzle so to speak. With a reasonable grasp of the overall, then it then much easier to understand the details.

This may not fit you but I find that it works for me very well. Just looking at bits and pieces only tends to confuse me and I get confused enough without any extra help.


Take care guy,

Dizfriz

Amtram
03-22-13, 09:17 PM
Would you humor us and give a straight answer as opposed to a paragraph of writing who's only purpose is to undermine those who do not agree with you.

Unfortunately, since you ask so many questions that are not even wrong, I am making the assumption that you do not understand, which is a far cry from making a self-aggrandizing statement like the one you accuse me of. Because of this, there is almost never any way to answer you that would require less than several years worth of instruction, which is how I came by my knowledge in the first place.

At least I attempt to respond to the points that might not line up with my thinking with what I have found to be strong supporting evidence. I would not consider that to be "undermining," whereas I would qualify aggressively challenging people, demanding answers to unanswerable questions, and denigrating their intelligence to be much more suited to that description.

Fyi I am not ruling anything out, genetic understanding is prerequisite for epigenetic understanding, it is you who are limiting scope here by ruling out epigenetics...

Statements like these clearly illustrate that you have made no effort to read what I actually say; they show that you have an agenda regarding me that requires inserting ideas that I've never entertained into a re-imagination of what I might have said if I were the pompous ignoramus. Therefore, I have even less impetus to try to provide you with any kind of information, since you won't actually read it, and my time will have been completely wasted.

Epigenetics influence before and after conception, you wish to rule out epigenetic factors all we ask is that you justify this view.

I cannot justify a view I don't hold.


Hope this isn't too much to ask.

Yes it is. Even if you asked nicely, which I have yet to see you do, it would be beyond the scope of my abilities to dumb myself down to these standards.

So I made an attempt to direct you to some excellent sources of information that would show you how epigenetics fits into the building of living creatures, and tried to reach out in a friendly way despite your unwavering disrespectful treatment of me, as a way of perhaps changing the tone of our interactions. It appears to me, from the tone of your posts, that you derive enough benefit in playing the role of an online bully that it precludes any desire to actually expand your knowledge base. This saddens me, because I feel that learning is its own reward. When I provide a source of information, it's because I find it useful, interesting, sometimes even exciting.

If you have already made the presumption that knowledge or information is automatically worthy of derision or dismissal simply because I was the one who provided it, that is your choice. But it would help the flow of conversation and the overall tone of discussion if you would ignore what I have to say rather than becoming bellicose every time I have the temerity to say something.

dvdnvwls
03-22-13, 09:39 PM
This may seem slightly tangential but maybe will help illustrate my point.

If you tickle the hind legs of a locust they turn from a solitary to an extremely social creature capable of creating massive swarms, they have exactly the same genetics, environmental stimuli increase seratonin levels and totally change their behaviour( and in this case even physical appearance, a change that is reversible...)

Metamorphosis of the mind...
It's apparently necessary to crowd the locusts together as well.


If you put a large group of young men into a small space and (optionally) tickle their hind legs, you can totally change their behaviour as well. (I'm sure their neurotransmitter levels change as well, though I haven't tested that.) Behaviour change due to circumstances and stimulation doesn't require epigenetics as an explanation.

Tyler Durden
03-23-13, 10:18 PM
Funny thing is Amtram, things you accuse me of, you are quite blatantly guilty of yourself, but I think I am going to bow out of this conflict

dvdnvwls, there was no mention of epigenetics in that post.

It was just an example of relatively minor environmental changes resulting in significant alterations to behaviour and physiology.

mildadhd
03-23-13, 10:26 PM
Is the biology of behavioral addiction,

similar to the biology of ADD ,epigenetically?

Tyler Durden
03-23-13, 10:34 PM
Yes, I believe the similarities are quite obvious. They are both behavioural, they are both stress sensitive, neurotransmitter associations etc.

Conman
03-23-13, 11:36 PM
Sir!!!

SB_UK
03-24-13, 11:33 AM
The down side of finding the genes is highly related to the up side ?

SB_UK
03-24-13, 11:37 AM
ps 10 years ago I presented the 'up side' (pro-stance) to which the response was the 'down side' that - 'well, this isn't actually science'.

I agreed.

We call this 'hoofing' the ball up field and hoping that it'll land at the feet of one of our players.
Never does though.

Proper science is much more elegant than anything '-omic'.

SB_UK
03-24-13, 12:12 PM
Basic idea:

Stamp-collecting in the post-omic playground (http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&cad=rja&ved=0CEoQFjAE&url=http%3A%2F%2Fjournals.sfu.ca%2Fhypot%2Findex.p hp%2Fmain%2Farticle%2Fdownload%2F8%2F8&ei=7CNPUez5Femd0wWHwYHYAQ&usg=AFQjCNEo6-NiLtBizzFmVjqmn2RYotV0-A&sig2=3d6G6Ay6J9cfTErcReJXag&bvm=bv.44158598,d.d2k)

Are we merely stamp-collecting , mindlessly collecting useless details ?There are two kinds of science, "physics" and "stamp-collecting."

He's not suggesting stamp-collecting is - just that it masquerades as being.

Proper science is tough - and, I'm not entirely sure - requires much empirical experimentation.

-*-

When the idea appears in standard scientific press ... ... we know that the game is up.

Genetics smenetics.
Not even epigenetics smenetics.

We're looking just at suffering through pure and plain environmental factors - caused by environmental factors introduced by man.

We actually literally 'do it to ourselves' and can choose not to 'do it to ourselves' if we wish.

However - we've a zillion machines which're primed to sequence the lesser spotted right handed parakeet ... ... and you never know, the secret of a society without repression might be spelt out half way down the long arm of chromosome three.

'TATA CA...'

Tyler Durden
03-24-13, 04:21 PM
This thread shouldn't be under ADHD let alone scientific discussions, the OP is not relevant to ADHD, genes that cause ADHD have not been identified, and never will be, as they do not exist.

Amtram
03-24-13, 05:18 PM
Genes that affect dopamine regulation are responsible for some of the symptoms of ADHD, and they have been identified, and this was a story about the effect of a gene that regulates dopamine processing.

Joel Nigg has also published research and presented the findings of other researchers that have identified the genes that build several other sections of the brain that are implicated in other symptoms of ADHD and related disorders.

Imaging studies have produced evidence of structural and/or functional differences related to symptoms, and genes have been tested on lab animals and have been found to regulate the formation of those structures. Further research has shown a correlation between gene presence and brain structure in humans.

Since the symptoms of ADHD originate from more than one area of the brain, not just the frontal lobes, we need to understand what roles other sections of the brain perform. Since genes do more than just build a single piece of the brain, finding what else a gene does helps us understand co-existing conditions and other symptoms that might be caused by the same gene, and how to treat something that's a problem without doing more harm than good.

You cannot state with authority that the "genes for ADHD" will never be found. If all you're looking for is the "genes for ADHD," then a lot of other things won't be found, either. The entire process is a lot more complex than finding the "genes for ADHD."

If we do research and experimentation, we often learn more than what we were originally looking for. This story is an illustration of that, and how there are overlaps in genes, and brain function, and neurological conditions, and findings in one can benefit understanding and treatment not only of that one, but of the others as well.

That is science, and it does relate to ADHD, if you understand science and keep up with the research.

Tyler Durden
03-24-13, 05:35 PM
I am glad you appreciate the complexity, I hope you also understand why this complexity would massively limit the usefulness of "identifying the genes" and that this complexity stems primarily from environmental interactions and epigenetics.

This thread is called "the upside of finding the genes"...

I am curious what do you consider has been "the up side" to identifying genes with regard to ADHD in all the years of research?

Tyler Durden
03-24-13, 05:51 PM
To use the analogy used by SB_UK earlier, unlike the OP which is the identification of a single gene, identifying ADHD genes is like identifying pieces smashed glass, it serves little purpose on its own.

Prevention and mitigation requires environmental understanding, such genetics without context are meaningless.

Amtram
03-24-13, 05:55 PM
So then I may correctly assume that you would also like all research into cancer defunded? After all, cancer is complex, and we will never find a "cure for cancer." And since we haven't so far, then there's been no up side to anything we've discovered during cancer research.

Glad you cleared that up. If something being complex makes it pointless to look at the most likely causes or investigate possible treatments, then it's even more pointless to research cancer than it is to research ADHD. I don't think this view is going to make you very popular, though.

Tyler Durden
03-24-13, 06:12 PM
Not at all, complexity requires research to be meaningful and intelligent.

Genetic research into cancer is also less intelligent than environmental research.

Let's use lung cancer as an example.

What is more significant, environmental factors such as smoking, or the best genetic research would be able to muster and identifying genetics that posed a higher risk of lung cancer?

http://www.cancercouncil.com.au/31924/reduce-risks/smoking-reduce-risks/tobacco-facts/the-tobacco-industry-a-history-of-denial/?pp=31924

I am not saying genetic research has no relevance, it just has far less relevance, especially with regard to ADHD.

Lunacie
03-24-13, 06:43 PM
Not at all, complexity requires research to be meaningful and intelligent.

Genetic research into cancer is also less intelligent than environmental research.

Let's use lung cancer as an example.

What is more significant, environmental factors such as smoking, or the best genetic research would be able to muster and identifying genetics that posed a higher risk of lung cancer?

http://www.cancercouncil.com.au/31924/reduce-risks/smoking-reduce-risks/tobacco-facts/the-tobacco-industry-a-history-of-denial/?pp=31924

I am not saying genetic research has no relevance, it just has far less relevance, especially with regard to ADHD.

Genetic research may eventually explain why some smokers get lung cancer
or mouth cancer, and some don't. It may not. We won't know until it's tried.

Tyler Durden
03-24-13, 08:36 PM
Would you kindly explain what other meaningful reason there might be for researching genes with regard to ADHD other than etiological understanding or anything that could be referred to as corrective or preventative measures?

meadd823
03-25-13, 01:03 AM
Enough -


http://i153.photobucket.com/albums/s206/tlr823/borrowed%20small%20pics/moderator%20expressions/cat-on-computer.jpg

Until review is completed by science section moderators both of whom have to work tomorrow. .. . so I suggest members in conflict take this time to cool their jets and figure out better ways to communicate with each other gong forward!!!

meadd823
03-26-13, 02:42 AM
http://i153.photobucket.com/albums/s206/tlr823/borrowed%20small%20pics/moderator%20expressions/Preview-5_zps3627534e.jpg


Thread re-opened = Please remain on topic which is

"The upside of finding genes"

Meaning the thread is to discuss genetic studies and the impact these studies have had upon our lives.

I have done a bit of editing in order to remove off topic bits and those who serve no purpose to the topic at hand however some off shoots may still be present due to possible relevance if pursued appropriately


This is NOT about money, societies ills, or environmental influences causing ADD.

Should you wish to discuss any thing but the upside of finding genes please begin your own thread.

Due to frequent conflicts and thread derailments IN this section it has become obvious that staying on topic is paramount to a productive discussion To that end moderating is going to become stricter regarding this guideline.

Please refrain from introducing another topic especially if the same topic has or is being discussed else where.

Tyler Durden
03-28-13, 06:48 PM
This post is not intended to be antagonistic i genuinely wish to understand what real progress has been made due to these discoveries.

Genes that affect dopamine regulation are responsible for some of the symptoms of ADHD, and they have been identified, and this was a story about the effect of a gene that regulates dopamine processing.



What have been the positive repercussions of these findings for people with ADHD?



Joel Nigg has also published research and presented the findings of other researchers that have identified the genes that build several other sections of the brain that are implicated in other symptoms of ADHD and related disorders.



What have been the positive repercussions of these findings for people with ADHD?



Imaging studies have produced evidence of structural and/or functional differences related to symptoms, and genes have been tested on lab animals and have been found to regulate the formation of those structures. Further research has shown a correlation between gene presence and brain structure in humans.



What have been the positive repercussions of these findings for people with ADHD?



Since the symptoms of ADHD originate from more than one area of the brain, not just the frontal lobes, we need to understand what roles other sections of the brain perform. Since genes do more than just build a single piece of the brain, finding what else a gene does helps us understand co-existing conditions and other symptoms that might be caused by the same gene, and how to treat something that's a problem without doing more harm than good.



What repercussions would their be for improving this understanding? ADHD lobotomies?



You cannot state with authority that the "genes for ADHD" will never be found. If all you're looking for is the "genes for ADHD," then a lot of other things won't be found, either. The entire process is a lot more complex than finding the "genes for ADHD."



I think it is not particularly controversial to say that there is no direct association between specific genes and ADHD, they are risk factors at best.

The reason for this complexity is obviously environmenalt influence in genetic expression.

If you believe that not to be the case, what more plausible explanation would you give?


If we do research and experimentation, we often learn more than what we were originally looking for. This story is an illustration of that, and how there are overlaps in genes, and brain function, and neurological conditions, and findings in one can benefit understanding and treatment not only of that one, but of the others as well.

That is science, and it does relate to ADHD, if you understand science and keep up with the research.


I am all for increasing understanding of genetics, after all it is a fascinating subject, however,

I just wished to hear what real upsides you expect there to be as that was the title of the thread.

What is a best case scenario for instance?

I did not dispute that genetics relate to ADHD, it is an implicit assumption, my point is that genetic research over the last 20 years or however long it has been has resulted in no REAL progress, and infact the epidemic has gotten WORSE, to me that sounds like the OPPOSITE of progress.

Amtram
03-28-13, 09:02 PM
This post is not intended to be antagonistic i genuinely wish to understand what real progress has been made due to these discoveries.



What have been the positive repercussions of these findings for people with ADHD?



What have been the positive repercussions of these findings for people with ADHD?



What have been the positive repercussions of these findings for people with ADHD?



What repercussions would their be for improving this understanding? ADHD lobotomies?

Funny, this looks just as antagonistic as every other time you've bullied me in public, asking the same question over and over, showing that you have cherry-picked a few words here and there from what I've said without actually paying attention at all. And where in creation did you come up with the idea of lobotomies being a reasonable treatment option for anything, much less something I would endorse?

You see, I can explain and provide sources until I'm blue in the face and you come back to these repetitious questions that show that you've decided what you want me to be saying without reading what I've said.

Where have I failed to explain that knowledge progresses from one finding to another? What happened to understanding that there's been a scientific connection made between dopamine processing and ADHD? When have Joel Nigg's extensive findings about ADHD lost their relevance? How difficult is it to understand that imaging studies that show differences in brain functions can be used to help people who have differences in brain function? What part of my explanations that we've learned about functions of specific areas of the brain from traumatic brain injury would suggest that I view causing brain injury to be a therapeutic practice?



I think it is not particularly controversial to say that there is no direct association between specific genes and ADHD, they are risk factors at best.

The reason for this complexity is obviously environmenalt influence in genetic expression.

If you believe that not to be the case, what more plausible explanation would you give?

As I've said before, the only people who believe there's such a thing as genetic determinism are people who don't understand genetics. Risk factors become more suspect the higher their correlation with outcome. ADHD is so highly heritable that ignoring the genetic correlation is cutting off your nose to spite your face. Environmental influence in genetic expression is rare compared to normal development, and most of the epigenetic process is heritable. To state that "obviously" environmental influence is behind ADHD requires ignoring the fact that no shared environmental factor has yet come anywhere close to having the statistical correlation of genetics. If we were to find something that did, it would be worth studying, but to keep throwing resources at something that has shown marginal results instead of something that has shown a significant potential is ludicrous.



I am all for increasing understanding of genetics, after all it is a fascinating subject, however,

I just wished to hear what real upsides you expect there to be as that was the title of the thread.

What is a best case scenario for instance?

The upside is that people can be tested genetically and find out what is really wrong with their brains instead of diagnosing problems exclusively by symptoms. The upside is that genetically-targeted treatments can be prescribed, eliminating the trial and error procedure we have now for medication. The upside is that new treatments can be discovered that we already know are safe. If you had read the article, you would see that the effective treatment was originally formulated for a completely different condition that just happened to be caused by the same gene.

So, for example, if we were to discover a genetic connection between the pancreas and the brain that caused the glucose metabolism problem that some people have hypothesized as an underlying cause of ADHD, then perhaps medications for hypo or hyperglycemia could be an effective treatment for people with that form of the disorder - instead of stimulants, antipsychotics, and antidepressants. Without the genetic information, we will continue to treat symptoms only, and prescribe based on general information.

That you are not figuring this out yourself indicates to me that you are doing nothing but looking for an opening to be antagonistic. If you were not intending to be antagonistic, these things would have been patently obvious.

I did not dispute that genetics relate to ADHD, it is an implicit assumption, my point is that genetic research over the last 20 years or however long it has been has resulted in no REAL progress, and infact the epidemic has gotten WORSE, to me that sounds like the OPPOSITE of progress.

There is no epidemic. Diagnoses have gone up primarily because adults are being diagnosed for the first time, and partly because diagnostics have improved. Same as for autism. New diagnoses are coming from undiagnosed adults and improperly diagnosed children ("mental retardation" is going down correspondingly as a diagnosis, for example) not from some sudden surge in cases.

Genetic research has had nothing to do with this, as it is not at the point yet that it can be used for diagnostic purposes. Diagnostic and treatment research and genetic research on ADHD have been going on in a more parallel direction thus far, occasionally coming close to touching, but neither actually driving a significant change in the other. Genetic research has not created an epidemic of ADHD.

Tyler Durden
03-28-13, 11:31 PM
I thought I asked politely

It was a genuine request, one you have yet again declined.

I was asking primarily for you to state the real upsides.

Not just potentially fantasy upsides.

But given your reply it is apparently too much to ask

Lunacie
03-29-13, 10:19 AM
I thought I asked politely

It was a genuine request, one you have yet again declined.

I was asking primarily for you to state the real upsides.

Not just potentially fantasy upsides.

But given your reply it is apparently too much to ask


Amtram did answer your questions about the upside of gene mapping.

At one time the idea that germs existed and lack of sanitation was causing
widespread illness was also considered "fantasty."

Tyler Durden
03-29-13, 10:32 AM
WTF have germs got to do with anything? Never heard of someone fantasising about the existence of germs and even if they did it has NO relevance nobody debates the existence of genes.

No she did not give a single straight answer.

Please could you highlight where she explained the benefits of those discoveries?

Where she clearly shows the upsides to 20 years of genetic research on ADHD etiology, and preventative or corrective measures?

Or where she provided any evidence that the problem is not getting worse instead of better?

Lunacie
03-29-13, 10:55 AM
WTF have germs got to do with anything? Never heard of someone fantasising about the existence of germs and even if they did it has NO relevance nobody debates the existence of genes.

No she did not give a single straight answer.

Please could you highlight where she explained the benefits of those discoveries?

Where she clearly shows the upsides to 20 years of genetic research on ADHD etiology, and preventative or corrective measures?

Or where she provided any evidence that the problem is not getting worse instead of better?

There were a lot of people who thought the idea of germs that cannot be
seen by the human eye was a fantasy. They did debate the existence of
germs and the dangers they pose. But in time it became clear what the
upside is for preventing disease by stopping the spread of germs.

I don't think I've ever met anyone else who had such a difficult time with
the concept of analogies and comparisons.

My quoting Amtram's post isn't going to change anything she wrote or
make it easier to understand. It's right there for you to read, and it's up
to you whether you accept the potential upside in gene mapping.

Tyler Durden
03-29-13, 11:01 AM
How is people not believing germs exist an effective analogy?

Nobody here is debating the existence of genes

(or that some genes show a correlation with ADHD....)

It is repercussions of these findings that is being questioned.

You said she answered the questions, she did not.

If you maintain she did then you would be able to point out where, if you cannot then the implication is that she did not.

meadd823
03-29-13, 11:26 AM
I have never done this as a moderator but apparently question clarification is warranted to prevent topic derail


Where she clearly shows the upsides to 20 years of genetic research on ADHD etiology, and preventative or corrective measures?


The topic is the upside to finding genes Tyler is trying to connect this upside to finding genes with regards to ADHD treatment, understanding of causes, or prevention of impairments which he sees as relevant to this ADD support community.

I am moderating the thread therefore neutral in this matter. I am unable to offer my own point of view however I am hoping by clarification of the question being asked further conflicts and topic derailment can be avoided.

Participating members are free to respond as they wish within the guidelines but please remember enforcement as to topic adherence is stricter in this section as per community members request.

Lunacie
03-29-13, 11:33 AM
How is people not believing germs exist an effective analogy?

Nobody here is debating the existence of genes

(or that some genes show a correlation with ADHD....)

It is repercussions of these findings that is being questioned.

You said she answered the questions, she did not.

If you maintain she did then you would be able to point out where, if you cannot then the implication is that she did not.

Even when the microscope proved the existence of germs, many did not
believe they could cause infection or disease, or understand the possibility
of prevention of infection and disease by hand washing and sanitization.

I don't see how I can make the analogy to gene mapping and possilbe
prevention and better treatment for mental health disorders like ADHD.

No, the implication is that you don't understand Amtram's answer. Here is
what she said, and if this doesn't answer your questions clearly, then
perhaps you aren't being clear in what you're asking.


The upside is that people can be tested genetically and find out what is really wrong with their brains instead of diagnosing problems exclusively by symptoms.

The upside is that genetically-targeted treatments can be prescribed, eliminating the trial and error procedure we have now for medication.

The upside is that new treatments can be discovered that we already know are safe.

If you had read the article, you would see that the effective treatment was originally formulated for a completely different condition that just happened to be caused by the same gene.

So, for example, if we were to discover a genetic connection between the pancreas and the brain that caused the glucose metabolism problem that some people have hypothesized as an underlying cause of ADHD, then perhaps medications for hypo or hyperglycemia could be an effective treatment for people with that form of the disorder - instead of stimulants, antipsychotics, and antidepressants.

Without the genetic information, we will continue to treat symptoms only, and prescribe based on general information.

Tyler Durden
03-29-13, 11:51 AM
Those upsides are all theoretical.

They are not benefits we have seen from 20 years of genetic research.

There are no real life examples of them with regard to ADHD treatment, ergo they are STILL hypothetical, those benefits do not exist.

And there is still nothing regarding preventative measures or etiological understanding ( requisite for alternatives to symptom treatment).

Lunacie
03-29-13, 12:13 PM
Those upsides are all theoretical.

They are not benefits we have seen from 20 years of genetic research.

There are no real life examples of them with regard to ADHD treatment, ergo they are STILL hypothetical, those benefits do not exist.

And there is still nothing regarding preventative measures or etiological understanding ( requisite for alternatives to symptom treatment).

While we're still in the early stages of gene mapping, I do think we've
gotten past the point of mere theory. The cost of doing this research was
nearly prohibitive until recently and that has prevented the kind of benefits
we would all like to see from being available already. I think they will come
as advances in this research become more affordable.

SB_UK
03-29-13, 12:27 PM
While we're still in the early stages of gene mapping, I do think we've
gotten past the point of mere theory. The cost of doing this research was
nearly prohibitive until recently and that has prevented the kind of benefits
we would all like to see from being available already. I think they will come
as advances in this research become more affordable.

If we accept that genetics will deliver what ADHD geneticist believes it will ? Then what is it that ADHD geneticist expects to see happen ?

The location of 5 broken genes - where if you have 2 broken genes you'll get ADHD ?
Parental screening to give prospective parents a percentage likelihood that their children will have ADHD ?
Early testing/abortion if an ADHD child is being carried ?

Those are the types of things that clinical geneticist deals in - are those the outcomes which the genetics community are dreaming of one day offering to ADDers ?
That is - testing/likelihood/abortion.

Lunacie
03-29-13, 12:59 PM
If we accept that genetics will deliver what ADHD geneticist believes it will ? Then what is it that ADHD geneticist expects to see happen ?

The location of 5 broken genes - where if you have 2 broken genes you'll get ADHD ?
Parental screening to give prospective parents a percentage likelihood that their children will have ADHD ?
Early testing/abortion if an ADHD child is being carried ?

Those are the types of things that clinical geneticist deals in - are those the outcomes which the genetics community are dreaming of one day offering to ADDers ?
That is - testing/likelihood/abortion.

I posted a link to an article in TIME magazine a few months ago asking
those very questions. Here it is again: http://www.time.com/time/covers/0,16641,20121224,00.html

SB_UK
03-29-13, 01:00 PM
Tyler is trying to connect this upside to finding genes with regards to ADHD treatment, understanding of causes, or prevention of impairments which he sees as relevant to this ADD support community.

understanding of causes
I think that there's an upside to not finding genes - which does, to be fair, require that we look.
What's the upside to not finding genes ?
We have to look elsewhere.

But why not look elsewhere from the outset ?
Well - people aren't really going to like where we're going to have to look to eliminate the disorder element of ADHD.

Failing to find the genes will result in an understanding of causes - by forcing us to look elsewhere ?
It is difficult presenting a pro-genetics perspective so bear with me :).

If there are two routes to the supermarket - down a chute which'll take a second or walking which'll take 5 minutes - I guess the chute should be tried first
... ... however when we try the chute several times over and pass the 5 minutes required to walk to the supermarket ... ... ...

prevention of impairments
Well - if we've nowhere else to look (have ditched genetic and pharmaceutical approaches) - then we concentrate all minds on changes to environmental context to prevent impairments.

-*-

So - there's a very great upside to not finding the genes ?
We concentrate all effort on an intervention (environmental) which works.
Noting - that many geneticists were epidemiologists before the darkside called them ... ... and so they won't be terribly fussed about reverting.

SB_UK
03-29-13, 01:08 PM
I posted a link to an article in TIME magazine a few months ago asking
those very questions. Here it is again: http://www.time.com/time/covers/0,16641,20121224,00.html

At the outset of molecular genetics / genetics - the hope was that we'd find something broken and we'd fix it
- job done.

Didn't work out that way though.

Where's the end-game ?

If we assume that genetics is not going to lead anywhere - where's the point that geneticist will throw up their hands in the air and admit it.

Thing is - is that that time is never.

There'll always be another experiment to perform.

That's the unfortunate side to medical research - its open-endedness.

Ideally science should limit the possibilities so we converge on an answer - not result in an exponentially increasing number of questions - with each screen.

Lunacie
03-29-13, 01:13 PM
I have never done this as a moderator but apparently question clarification is warranted to prevent topic derail





The topic is the upside to finding genes Tyler is trying to connect this upside to finding genes with regards to ADHD treatment, understanding of causes, or prevention of impairments which he sees as relevant to this ADD support community.

I am moderating the thread therefore neutral in this matter. I am unable to offer my own point of view however I am hoping by clarification of the question being asked further conflicts and topic derailment can be avoided.

Participating members are free to respond as they wish within the guidelines but please remember enforcement as to topic adherence is stricter in this section as per community members request.

I hope I don't get in trouble for responding to a green post, but . . .

I don't see why it was even a question when Amtram stated her opinion
in the very first post.

While a condition that has multiple genes involved [i.e. ADHD] is not going to be so straightforward when it comes to finding causation or making diagnosis, these advances with monogenic conditions put us a step closer each time they're detected and isolated.

That's why genetics is important.

She did not make any claims about breakthroughs in regards to gene
mapping and ADHD treatment, understanding of causes, or prevention
of impairments. She's exctited about the future possibilities. I am too.

It's too bad we aren't further along in this kind of scientific knowledge,
but as I mentioned before, the costs were prohibitive until recently and
I expect scientists were using what money they had for research into
diseases and disorders that are known killers.

Tyler Durden
03-29-13, 02:34 PM
Questionning a moderator action in public...

Amtram did not answer the questions as they were posed.

I was highlighting how this is a theoretical discussion at best with regard to adhd, and at worst a moot point/thread.

Amtram
03-29-13, 02:36 PM
Just because the goalposts get moved every time I try to answer doesn't mean I haven't answered.

Making progress towards discovery, or making a discovery that has potential to open up new knowledge, better treatments, better diagnosis, is an upside. Every single major scientific discovery ever made started off with smaller discoveries, which were then put together, or which led to new avenues of thinking, or which answered questions that had been looked at from other angles without prior success. The knowledge constantly builds on itself, and there is no end.

The idea that a piece of scientific discovery is useless if it doesn't finally answer everything else, whether it's related or not, is simply wrong. There is incredible value in each new, valid piece of information, outside of its direct connection to what is being studied.

If you look at the article, and read my responses, you'll see that the genes in question do more than just cause this rare disorder, and they build more than just dopamine receptors, and that in the brain, they are related to several other conditions that are affecting millions of people. Knowing this information does not give us everything we know to treat, prevent, predict, or cure any of them, but it puts us closer to knowing that - by giving us a piece of the larger body of information we need in order to do so.

This is basic. This is how science works. Heck, this is how lots of things work besides science. Life is a giant jigsaw puzzle that came in a black plastic bag - you don't know what it's shaped like, you don't know how many pieces there are, and you don't know what the picture is supposed to look like when it's done. So you put together the pieces that fit, try some that don't and set them aside for later, and bit by bit you get larger sections completed. You can sort them by color or shape, but that doesn't mean they'll connect or even be close to each other in the final puzzle - but they fit into it somewhere in the end, and you're more likely to put a section together by sorting pieces by what colors they have in common.

By saying that none of this information is relevant, it's like saying that completing an edge or connecting a dozen puzzle pieces has put you no closer to solving the jigsaw puzzle than just leaving them all in the bag.

Tyler Durden
03-29-13, 02:40 PM
Again you have disregarded what I said.

Sprouting wings and being able to fly is also an upside.

It is just not very likely.

And it is at best HYPOTHETICAL.

There is far more solid science with actual real world potential and extensive positive ramifications for adhd in the theoretical section, all this highlights is genetic research bias.

Lunacie
03-29-13, 02:46 PM
Questionning a moderator action in public...

Amtram did not answer the questions as they were posed.

I was highlighting how this is a theoretical discussion at best with regard to adhd, and at worst a moot point/thread.

I think Amtram did her best to explain. You cannot compel anyone to
answer questions in a specific manner. We all do the best we can to have
a good discussion.

If you feel like the topic is too theoretical to be of value (and I disagree
with you there), then why bother posting and asking questions?

Amtram
03-29-13, 02:47 PM
Then you have not been following the science. I get updates from NIGMS and Nature all the time with significant new genetic findings, so there is solid evidence out there that genetic research is producing tangible and applicable results. I suppose if you don't know what's happening, it's easy to think that nothing is happening.

mildadhd
03-29-13, 02:53 PM
I haven't been reading this thread.

Sorry if I repeat what someone else has already said.


I think the upside of finding genes that are sometimes related to ADD can help to point to the environmental factors that are involved in expressing these genes.


Although is important to note that ADD is caused by multifactors,

and that not all people with ADD seem have all of these genes,

and sometimes people with these genes don't have ADD.

Why not?

In my opinion it is because environment is the decisive factor in gene expression.

ADD is epigenetic.

Dizfriz
03-29-13, 03:19 PM
What is the upside of finding the genes?

Let us look at heredity as a factor in ADHD

The data is from the Coursera "Pay Attention!!" ADHD Through the Lifespan, University of Pennsylvania Lesson 2-Causal Factors.


"ADHD is considered as a complex genetic disorder" This is the basis for the course and most of the research. ADHD is a complex interaction of genetics and environmental impact on the genetics. If you do not understand this, you will not understand ADHD. It is that simple.

That does not mean that other factors are ignored. In the video, it was emphasized that the most exciting current research path is exploring the reaction of the environment on genetics. It was stated that ADHD was "Genes and environment over time" which sounds to me to be a very good description.

So to some stats:

ADHD is considered to be somewhere between 60-75% hereditary and 25-35% stemming from CNS injury.

Heritability factors in mental health: ADHD 75% Schizophrenia 80-85% Autistic like traits 82% to 87% Panic Disorder 43%

Acquired ADHD: 3-7%

If a parent is ADHD here is around a 40-45% chance of any given child being ADHD, an 8 fold factor over the general population.

Identical twins: ADHD 78-92% heritable

According to the video, genetics explains around 88-92% of the variance of ADHD using the DSM.

So you can see that genetics is clearly the largest factor in the causation of ADHD. That is pretty much a scientific fact and I know of no one in the field disputing this. So, if genetics is this biggest factor with ADHD, it is where the bulk of the research emphasis should be. That does not mean that other areas should not be looked at but for results, genetics/neurological causes are the way to bet.

Finding the genes is part of an ongoing process that in the past 30 years has taken us from knowing little about the disorder and having no treatment except a few stimulant medications to some effective tools and a real chance of gaining an understanding of what causes ADHD both neurological and environmental. If these studies are not done then we will have little or no progress and we shall fewer effective tools available-a real tragedy if this should happen. Studies are directed at the future as is where most research in this and similar areas is done. Science is focused on discovering new things that can have an impact.


For ADHDers I can think of no more important line of research than this. Other areas are also important but genetic/neurological research has, by far, the best chance of showing results.

I would encourage enrolling in the course. So far it has been very good. The speaker is not the most dynamic in the world but I am interested in the data and that is not really an issue with me.


Take care,

Dizfriz

As an aside for Peri, it was noted in the video that high maternal anxiety in the second trimester may have some impact. It was not discussed and there were some question marks after the statement but I thought it might be something you would be interested in.

Diz

mildadhd
03-29-13, 03:41 PM
What is the upside of finding the genes?

Let us look at heredity as a factor in ADHD

The data is from the Coursera "Pay Attention!!" ADHD Through the Lifespan, University of Pennsylvania Lesson 2-Causal Factors.


"ADHD is considered as a complex genetic disorder" This is the basis for the course and most of the research. ADHD is a complex interaction of genetics and environmental impact on the genetics. If you do not understand this, you will not understand ADHD. It is that simple.

That does not mean that other factors are ignored. In the video, it was emphasized that the most exciting current research path is exploring the reaction of the environment on genetics. It was stated that ADHD was "Genes and environment over time" which sounds to me to be a very good description.

So to some stats:

ADHD is considered to be somewhere between 60-75% hereditary and 25-35% stemming from CNS injury.

Heritability factors in mental health: ADHD 75% Schizophrenia 80-85% Autistic like traits 82% to 87% Panic Disorder 43%

Acquired ADHD: 3-7%

If a parent is ADHD here is around a 40-45% chance of any given child being ADHD, an 8 fold factor over the general population.

Identical twins: ADHD 78-92% heritable

According to the video, genetics explains around 88-92% of the variance of ADHD using the DSM.

So you can see that genetics is clearly the largest factor in the causation of ADHD. That is pretty much a scientific fact and I know of no one in the field disputing this. So, if genetics is this biggest factor with ADHD, it is where the bulk of the research emphasis should be. That does not mean that other areas should not be looked at but for results, genetics/neurological causes are the way to bet.

Finding the genes is part of an ongoing process that in the past 30 years has taken us from knowing little about the disorder and having no treatment except a few stimulant medications to some effective tools and a real chance of gaining an understanding of what causes ADHD both neurological and environmental. If these studies are not done then we will have little or no progress and we shall fewer effective tools available-a real tragedy if this should happen. Studies are directed at the future as is where most research in this and similar areas is done. Science is focused on discovering new things that can have an impact.


For ADHDers I can think of no more important line of research than this. Other areas are also important but genetic/neurological research has, by far, the best chance of showing results.

I would encourage enrolling in the course. So far it has been very good. The speaker is not the most dynamic in the world but I am interested in the data and that is not really an issue with me.


Take care,

Dizfriz

As an aside for Peri, it was noted in the video that high maternal anxiety in the second trimester may have some impact. It was not discussed and there were some question marks after the statement but I thought it might be something you would be interested in.

Diz

Thanks,

I don't want to start a confrontation I agree with what you are saying,

except I don't agree with the high numbers for genetics.

The adoption twin studies don't consider stress pre and post natal.

In my understanding , infants in the last trimester are most affected by environmental stresses.

Maternal Anxiety and depression must also be considered, both pre and post natal.

I think a fair number is 50 : 50 (environment and genetics) = epigenetics

In regards to public awareness and treatment...etc, if these topics representing all ADDers.

Hereditary involves epigenetic factors.

SB_UK
03-29-13, 04:16 PM
The house of cards has fallen.

http://www.genetics.org/content/early/2011/10/03/genetics.111.131912

Genome-wide association studies have thus far failed to explain the observed heritability of complex human diseases. This is referred to as the "missing heritability" problem.

However, these analyses have usually neglected to consider a role for epigenetic variation, which has been associated with many human diseases.

We extend models of epigenetic inheritance to investigate whether environment-sensitive epigenetic modifications of DNA might explain observed patterns of familial aggregation.

We find that variation in epigenetic state and environmental state can result in highly heritable phenotypes through a combination of epigenetic and environmental inheritance.

These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance, and similar to those expected from genetic effects.

The results suggest that epigenetic variation, inherited both directly and through shared environmental effects, may make a key contribution to the "missing heritability". That's really all there is to say.

Missing heritability (from GWAS) leads to the unambiguous conclusion as stated above.

It really is game over.

And all geneticists know it.

Have (to be fair) known it for a while.

I'd argue the higher level of geneticists knew if from the start.

Lunacie
03-29-13, 04:52 PM
The house of cards has fallen.

http://www.genetics.org/content/early/2011/10/03/genetics.111.131912

That's really all there is to say.

Missing heritability (from GWAS) leads to the unambiguous conclusion as stated above.

It really is game over.

And all geneticists know it.

Have (to be fair) known it for a while.

I'd argue the higher level of geneticists knew if from the start.

Perhaps you should have highlighted this part as well:

These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance, and similar to those expected from genetic effects.

Geneticists are looking primarily at genes, as well as how things affect the
genes. It doesn't seem to be an either/or situation, and I don't think the
geneticists look at it that way. Really, was there a 'house of cards' to fall?

Amtram
03-29-13, 05:27 PM
Thanks,

I don't want to start a confrontation I agree with what you are saying,

except I don't agree with the high numbers for genetics.

You may not agree, but you're disagreeing with a large number of studies with high numbers of participants across different cultures, all coming up with the same conclusion. Decades of multi-generational studies, each confirming that the majority of people diagnosed with ADHD have parents, grandparents, aunts, uncles, and siblings who also have ADHD. Statistics can be manipulated to a point, but there is too much data that agrees to suggest that these numbers are not factual.

I think a fair number is 50 : 50 (environment and genetics) = epigenetics

Keep in mind that epigenetics happens regardless of environment - it begins the moment sperm and egg meet, even before implantation in the endometrium, and happens for every single human alive. It is a process that turns genes into differentiated cells, and happens no matter what environmental factors exist or don't exist.

Epigenetics is not an interaction of genes and environment - it is the production of cells as directed by DNA and driven by RNA which can, in some cases, be altered by intrusion of an environmental factor, but which proceeds primarily without regard to it.

Without genes, there is no epigenetics. Epigenetics is the creating of cells.

Environment is a completely separate issue. It can, possibly, in some cases, interfere with the creation of cells and result in cells that are different from the way they were instructed to turn out by genes. However, it can also have a positive or negative effect without impacting anything genetic.

For that reason, environmental factors such as specific chemicals have been investigated long before we were looking into genes, and are looked at for correlation based on their own properties. Cigarettes and alcohol and recreational drugs can cause damage to a human body without causing any changes in genes or even gene expression.

And by themselves, none of them have shown enough statistical significance to be considered to "cause" ADHD. None of them have come close to showing the same level of correspondence as familial inheritance.

In regards to public awareness and treatment...etc, if these topics representing all ADDers.

Hereditary involves epigenetic factors.

And epigenetics are hereditary because they are carrying out the instructions of DNA. They can get damaged by chemical interference, resulting in defective cells, but otherwise "epigenetics" describes making cells as directed by DNA.

This is yet another example of why it's important to understand that each piece of information is integral to that larger puzzle. There may be six (or six thousand. . .) degrees of separation, but you can't connect the puzzle without all the pieces that go between and join other parts together.

mildadhd
03-29-13, 05:40 PM
Perhaps you should have highlighted this part as well:



Geneticists are looking primarily at genes, as well as how things affect the
genes. It doesn't seem to be an either/or situation, and I don't think the
geneticists look at it that way. Really, was there a 'house of cards' to fall?


Lunacie,

I love the way the lines are numbered in the research!

http://www.genetics.org/content/early/2011/10/03/genetics.111.131912.full.pdf+html

What line # is your quote from?

Side Note: I think it would be great, if everything I read, everywhere, had the lines numbered like this great research link.

Also can anyone explain to me what the difference is between,

epigenetic expression and genetic expression?

Amtram
03-29-13, 05:51 PM
The house of cards has fallen.

http://www.genetics.org/content/early/2011/10/03/genetics.111.131912

That's really all there is to say.

Missing heritability (from GWAS) leads to the unambiguous conclusion as stated above.

It really is game over.

And all geneticists know it.

Have (to be fair) known it for a while.

I'd argue the higher level of geneticists knew if from the start.

I'm about halfway through this paper, and I don't know what you're getting at here. It's talking about heritable epigenetic susceptibility and environmental exposures to factors that interact with those heritable traits in disease phenotypes. Essentially, if individuals have a susceptibility to disease and are exposed to the disease trigger, they can develop the disease without having a gene for the disease.

I don't see the conflict here. It's supporting heritable epigenetic traits and saying that if you've inherited the epigenetic susceptibility and are exposed to the factor that causes myelation, the disease happens. It also says that in some cases disease can be caused by environment alone. It also says that heritable epigenetic traits without the environmental trigger can result in no disease.

One snippet:

Our dynamical model has a most remarkable property in the case of environmental inheritance and environment-sensitive epigenetics, namely the possibility of the stable presence of a serious, heritable, early onset,
and common disease in a population. Purely genetic transmission of such a disease would induce strong natural selection against the risk alleles, with decreasing disease incidence through time, unless this evolutionary eff ect were balanced { as in the case of the balance between the eff ects of malaria and sickle-cell anemia. The high disease mortality in a particular environment will of course have demographic repercussions, but these could easily be balanced by immigration into the high risk environment { lung cancer in heavily smoking subcultures provides an illustration of this kind of eff ect. A new smoker could be considered a migrant into the smoking environment, and someone quitting smoking considered a migrant from the smoking to the non-smoking environment.

Essentially, it's saying that epigenetics can be heritable, too, and that environment-sensitive epigenetic traits can be triggered by environment. How is that "game over"? It's more like "game with two decks of cards instead of just one."

mildadhd
03-29-13, 05:53 PM
Keep in mind that epigenetics happens regardless of environment - it begins the moment sperm and egg meet- Amtram

I think environment has a mandatory presence, resulting in the sperm meeting the egg,

if you know what I mean.

Sperm meeting the egg is epigenetic.

Lunacie
03-29-13, 05:56 PM
I don't know which number those lines are in the article SB_UK linked.

I quoted them from the portion that he quoted from the article.

Amtram
03-29-13, 06:01 PM
That was the abstract. I'm looking at the full-text pdf. It has numbered lines that may be helpful for reading, but are a pain in the behind to edit out of a copy-paste.

Peripheral, "epigenetic expression" isn't really a thing, because epigenetics is a process of gene expression. I don't know if I gave you this link before, but you might find it helpful: Learn. Genetics (http://learn.genetics.utah.edu/content/epigenetics/) from the University of Utah.

mildadhd
03-29-13, 06:25 PM
That was the abstract. I'm looking at the full-text pdf. It has numbered lines that may be helpful for reading, but are a pain in the behind to edit out of a copy-paste.

Peripheral, "epigenetic expression" isn't really a thing, because epigenetics is a process of gene expression. I don't know if I gave you this link before, but you might find it helpful: Learn. Genetics (http://learn.genetics.utah.edu/content/epigenetics/) from the University of Utah.


This is from the link you just provided, titled Lick Your Rats.

Its not genetic, it's epigenetic.




"It turns out that the difference between a calm and an anxious rat is not genetic - it's epigenetic."


"The nurturing behavior of a mother rat during the first week of life shapes her pups' epigenomes. And the epigenetic pattern that mom establishes tends to stay put, even after the pups become adults"


Link below highly recommended,.


LICK YOUR RATS
Some mother rats spend a lot of time licking, grooming and nursing their pups. Others seem to ignore their pups. Highly nurtured rat pups tend to grow up to be calm adults, while rat pups who receive little nurturing tend to grow up to be anxious.

It turns out that the difference between a calm and an anxious rat is not genetic - it's epigenetic. The nurturing behavior of a mother rat during the first week of life shapes her pups' epigenomes. And the epigenetic pattern that mom establishes tends to stay put, even after the pups become adults

http://learn.genetics.utah.edu/content/epigenetics/rats/

Tyler Durden
03-29-13, 07:27 PM
Genes are determined at conception, you cannot change genes after conception.

Therefore identifying those associated with ADHD changes NOTHING, and history confirms this.

Just because something runs in families does not make it genetic.

There is no such thing as a 100% genetic case of ADHD.

The only way to alter the disorder is by focussing on the parts that can actually be altered and that is by altering their expression.

Gene expression is determined through epigenetics and environments therefore as this is the variable this is obviously where focus should be.

Therefore there is NO REAL WORLD upside to identifying the genes in disorders that are not monogenic such as ADHD, they are too complex and gene interactions require context to be meaningful i.e. environment/epigenetics

Identifying genes can only be useful in the real world when done in the context of the real world.

Amtram
03-29-13, 08:41 PM
Peripheral, the followup to those studies showed that the epigenetic changes were not heritable beyond the second generation. It is still useful as an example of how genetic expression can be changed through epigenetics.

It is also useful as an example of how one thing that influences gene expression by altering the epigenetic process can have much wider implications. The mice that were switched to other mothers actually changed appearance - therefore, the gene that related to emotional development, whose expression was susceptible to a change in environment, changed much more than just the emotional development. Imagine this applied to a creature much more complex than a mouse or a rat.

Just as with the cases in the original article in this thread, a gene can perform more than one task, and altering its expression (which is not so easy, actually, and depends on a lot of different factors) will change more than one thing. And that is why a medication that was in no way related to treating seizures alleviated the seizures of these three young people - because it alleviated the symptoms of a condition caused by the same gene but expressed in a different body part.

So - find a gene or two that's involved in creating one or more of the brain structures that is behind an ADHD symptom. . .find out what else that gene does. . .figure out what happens to that other body part during the epigenetic process to see if it's susceptible to an environmental factor, and when. . .

At that point, you have figured out one potentially important piece of information - whether the problem is caused by the regular, uninterrupted epigenetic process, or whether it's caused by the interference of an environmental factor. Therefore, you know something about whether it's genetic or environmental.

You have also started to figure out that you can look elsewhere in the body to find out if the symptom is based in brain structure, or has psychological causes. If this other part of the body shows the anomaly that you've found when the gene is expressed normally or when its expression has been altered, then you know that there's a physical anomaly in the brain, because the same gene builds both the body part and the brain part.

And the other thing you have found out is whether it is something that can be prevented, or if it's something that needs treatment. Because you've already teased out the information about whether it's normal genetic expression or an environmental factor that changes the genetic expression, you know whether the presence of the gene makes that environmental factor an exposure to be avoided.

Now, it's more likely that a gene is going to be involved in making several similar cells rather than a bunch of different ones. A gene that builds muscles will probably make muscle cells in several areas of the body rather than muscle cells and bone cells or muscle cells and thyroid cells, but that's why we're still looking at genes.

And since ADHD and most other psychiatric or neurological disorders and complex and have multiple symptoms and several areas of involvement in the brain, treatments based on genetics will initially be more useful for treating individual symptoms or symptoms based in the same area of the brain rather than entire conditions. That could be good - fewer side effects, less impact on brain functions that aren't involved. That could also be bad - the more symptoms you have, the more different kinds of treatments you need.

So this study, even though it turned out to not actually produce heritable epigenetic changes past a couple of generations, is still useful in giving us ideas on how to find out when a change is happening, how to recognize multiple changes brought on by the same gene, and how to measure whether a specific environmental factor actually has an effect on gene expression in the first place.

mildadhd
03-29-13, 08:54 PM
We're used to thinking of inheritance in terms of the letters of the DNA code that pass to us from our parents -- through eggs and sperm. But the licking rat story tells us that there is another path to the offspring's DNA. Through her licking behavior, a mother rat can write information onto her pups' DNA in a way that completely bypasses eggs and sperm.

http://learn.genetics.utah.edu/conte...genetics/rats/

Lunacie
03-29-13, 09:04 PM
Amtram, thank you again for helping me to understand what some of this
research is all about by putting in words I can relate to.
:thankyou:

mildadhd
03-29-13, 09:46 PM
Genes are determined at conception, you cannot change genes after conception.

Therefore identifying those associated with ADHD changes NOTHING, and history confirms this.

Just because something runs in families does not make it genetic.

There is no such thing as a 100% genetic case of ADHD.

The only way to alter the disorder is by focussing on the parts that can actually be altered and that is by altering their expression.

Gene expression is determined through epigenetics and environments therefore as this is the variable this is obviously where focus should be.

Therefore there is NO REAL WORLD upside to identifying the genes in disorders that are not monogenic such as ADHD, they are too complex and gene interactions require context to be meaningful i.e. environment/epigenetics

Identifying genes can only be useful in the real world when done in the context of the real world.


Stop making sense.

SB_UK
03-30-13, 05:29 AM
Perhaps you should have highlighted this part as well:



Geneticists are looking primarily at genes, as well as how things affect the
genes. It doesn't seem to be an either/or situation, and I don't think the
geneticists look at it that way. Really, was there a 'house of cards' to fall?

Not too sure why this is proving so hard to get across.

[1] We look for genes (broken proteins) in complex disorders and do not find them.
[2] We look at the heritability estimates and are left scratching our heads - because finding genes in highly heritable complex traits (should!) be as trivial as finding them in monogenic traits.
[3] We go back to the literature and find that high heritability can be caused by highly genetic or highly epigenetic/environmental influence.
[4] We conclude that the high heritability is definitely not caused by genes (because we've looked) and so accept the highly epigenetic/environmental model.

So - failure to find any broken genes in complex disorders can only result (because of the missing heritability problem) in accepting the line which Lunacie has just highlighted:
These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance, and similar to those expected from genetic effects. epigenetic = sensitivity (metabolic change)
x
environmental = stress (described previously - chronic psych. stress)

-*-

The house of cards to fall - is that human beings are genetically broken and therefore programmed from birth to fall victim to disease.

The epigenetic x environmental basis to high heritability complex disorders defines a small change in environmental infrastructure which'll eliminate disease.

We know that the environmental/epigenetic argument is correct because a 1000 year experiment where 'random' people are taken from across the globe and placed to live in a certain environment - do not get sick to any of the diseases of Western living.

Therefore there is no genetic influence - and environmental factors can overcome epigenetic susceptibility too.

Just environmental change is enough to eliminate human suffering.

Lunacie
03-30-13, 10:34 AM
SB_UK, disagreeing with your theory doesn't mean I don't understand it.

Researchers are finding different genes in people with disorders like ADHD.
It's complicated because it doesn't come down to just one gene. It's like
looking for the half-dozen puzzle pieces that are part of someone's face in
a puzzle with thousands of pieces, I'd hardly call it a "trivial" task.

[4] We conclude that the high heritability is definitely not caused by genes (because we've looked) and so accept the highly epigenetic/environmental model.

But that's not what it said in the quote I highlighted. Research shows that
genetics alone shows a similar causation as epigenetics/environment does.

Tyler Durden
03-30-13, 10:46 AM
Lunacie you are missing some important points.

One of which is that genes cannot be changed, just because you know a gene is linked to a disorder it doesn't change ANYTHING whatsoever, it is the equivalent to captain hindsight, or telling someone who has just been in a car crash that their injuries were likely caused by a car crash, bad analogy ill think of a better one after i finish posting no doubt.

Fact is there is little if any ACTUAL positive consequence to identifying the genes, it could in fact be detrimental as it distracts from what is actually important and can make a real difference and uses resources that would be better focussed elsewhere.

Lunacie
03-30-13, 11:12 AM
Lunacie you are missing some important points.

One of which is that genes cannot be changed, just because you know a gene is linked to a disorder it doesn't change ANYTHING whatsoever, it is the equivalent to captain hindsight, or telling someone who has just been in a car crash that their injuries were likely caused by a car crash, bad analogy ill think of a better one after i finish posting no doubt.

Fact is there is little if any ACTUAL positive consequence to identifying the genes, it could in fact be detrimental as it distracts from what is actually important and can make a real difference and uses resources that would be better focussed elsewhere.

Amtram pointed out that genetic expression can be changed through
epigenetics.

Gene research is beginning to lead to finding better treatments that are
tailored to each person, which could be positive in eliminating the long
and frustrating meds trials that people with ADHD go through now.

Amtram
03-30-13, 12:34 PM
I wonder if the resistance to exploring genetics would be the same if instead we were talking about, say, the fulcrum.

Why bother studying the fulcrum? All it's good for is see-saws and maybe lifting rocks.

It's never going to apply to anything else, it doesn't explain anything.

The mathematics that explain how it works can't possibly apply to anything else, so why bothering trying to find formulas for it? We just get more and more and more formulas, and then someone comes up with the bright idea of using them to figure out more formulas to "predict" speed and light and stuff, which we can tell about just by looking, and then they make this whole big deal about calling it "Physics."

What has Physics ever helped us with? I mean, we go to all this work making up formulas about how the fulcrum works and calculating force and torque and all that other stupid stuff, and all it does is give us more Physics. I don't use Physics in my daily life, so obviously it's useless and we're just throwing money away at research that doesn't do anyone any good. Can you honestly show how studying "Physics" has done anything except spend our tax dollars on useless research?

Instead of giving money to all these eggheads who sit around all day and play with numbers, we could be spending it on stuff like buildings and bridges and transportation and communication. If we hadn't wasted all that time with the stupid fulcrum, imagine how much more advanced we'd be right now!

/sarcasm

Tyler Durden
03-30-13, 01:14 PM
Lunacie,

This thread is not about everything that could in some tenuous way be linked to gene research, it is about "the up side of finding the genes."

Did you read my posts, regarding genetic expression?

Tyler Durden
03-30-13, 01:27 PM
It would be nice if someone would finally state in no uncertain terms exactly what an upside to finding the genes has been with regard to ADHD...

I mean surely that is the whole purpose for this thread... yet no ACTUALLY REALISED i.e. not hypothetical, upside has been specified, anywhere.

This is not proven science it is speculation.

Lunacie
03-30-13, 01:29 PM
Lunacie,

This thread is not about everything that could in some tenuous way be linked to gene research, it is about "the up side of finding the genes."

Just a side note but i think Amtram actually started a thread attempting to debunk epigenetics in relation to ADHD.

Well, that's what *I* have been discussing in this thread . . . the upside of
gene mapping and gene research. As I mentioned earlier, I read an article
in TIME magazine a few months ago that really caught my interest in this
topic. The article Amtram linked expanded on that topic and I've learned a
few more things here.

I would not speak for Amtram, but the impression I've gotten from reading
her posts (in this thread and others) is that she's delighted with research
and new knowledge in many areas including both genetics and epigenetics.

SB_UK
03-30-13, 01:33 PM
Research shows that
genetics alone shows a similar causation as epigenetics/environment does.
So an epigenetically inherited quality in a particular environment mimics the high heritability index seen in a classical monogenic character
- the null hypothesis (rejected) - that the high heritability in ADHD is caused by 'broken' genes should be interpreted in the world of science to accept the alternate hypothesis that it's an epigenetics/environmental interaction.

So - high heritability means either [Scenario 1] Genetic [Scenario 2] Epigenetic x Environment
[Scenario 1] REJECTED (by experimentation) - absolutely categorically by power analysis - leading us by default to acceptance of [Scenario 2] Epigenetic x Environment interaction as basis to High Heritability index.

It's just the basic scientific method.

Note though that there could be an incredibly large number of genes interacting very weakly to give ADHD (for which the exp. study wasn't sufficiently 'powered' to generate)
- but that's not a scenario which we can do anything about.

Besides - it's really not likely - one has to imagine how such a large number of genes could ever work themselves into a configuration to drive the emergence of a property which affects 5 - 15% of children.

It's either major gene effect or epigenetic x environmental - and major gene effect underlying complex conditions has been rejected.

It's easy to reject major gene effect - the experiment can literally ber performed start to finish in a couple of days.

APSJ
03-30-13, 01:38 PM
I've just read through this thread, and am finding it fascinating.

I am a little unclear on the points being debated, so wanted to see if I can clarify. I apologize if I missed something and acknowledge I haven't read much of the linked materials.


One of which is that genes cannot be changed, just because you know a gene is linked to a disorder it doesn't change ANYTHING whatsoever, it is the equivalent to captain hindsight, or telling someone who has just been in a car crash that their injuries were likely caused by a car crash, bad analogy ill think of a better one after i finish posting no doubt.

Fact is there is little if any ACTUAL positive consequence to identifying the genes, it could in fact be detrimental as it distracts from what is actually important and can make a real difference and uses resources that would be better focussed elsewhere.

The original post highlighted a concrete example of how knowledge of the genetic cause of a specific condition allowed for someone with that condition to be diagnosed and treated in a fashion that would not have been possible without such knowledge. It's not that we'll be able to somehow go in and 'fix' the genes, but that knowing them can direct appropriate treatment or reveal treatments that were not previously considered.

It doesn't seem like there's any contention that we're already at this point with ADHD, but the *potential* upsides do seem fairly clear:


The upside is that people can be tested genetically and find out what is really wrong with their brains instead of diagnosing problems exclusively by symptoms. The upside is that genetically-targeted treatments can be prescribed, eliminating the trial and error procedure we have now for medication. The upside is that new treatments can be discovered that we already know are safe. If you had read the article, you would see that the effective treatment was originally formulated for a completely different condition that just happened to be caused by the same gene.

So, for example, if we were to discover a genetic connection between the pancreas and the brain that caused the glucose metabolism problem that some people have hypothesized as an underlying cause of ADHD, then perhaps medications for hypo or hyperglycemia could be an effective treatment for people with that form of the disorder - instead of stimulants, antipsychotics, and antidepressants. Without the genetic information, we will continue to treat symptoms only, and prescribe based on general information.

As an example, due to genetics, some cases of ADHD are more related to reuptake issues and others with production of neurotransmitters. In the first case, Methylphenidate might be the be the better medication to start with as it works more as a reuptake inhibitor and an Amphetamine based med such as Adderol might be better in the second as it tends to enhance production of dopamine.

Is the point of disagreement, then, essentially, whether such benefits will materialize for ADHD, as they have for other disorders, because of the complexity of the genetic causes, the number of genes involved?

Is there reason to doubt the progress that's been cited so far toward these ends? The example Dizfriz cites seems to indicate that this research is actually getting close to yielding beneficial results already.

As far as focusing on epigenetics, gene expression, instead of genetics or the genes themselves, does an understanding of epigentic contribution to ADHD not presuppose understanding of genetic contributions? As stated in my prior post in this thread, I'm not at all conversant with these topics, but just looking at the simple definitions of these two fields, it would seem that looking at the impact of gene expression on ADHD would require us to know the genes whose expression affect ADHD.

SB_UK
03-30-13, 01:47 PM
As an example, due to genetics, some cases of ADHD are more related to reuptake issues and others with production of neurotransmitters. In the first case, Methylphenidate might be the be the better medication to start with as it works more as a reuptake inhibitor and an Amphetamine based med such as Adderol might be better in the second as it tends to enhance production of dopamine.If this is the best genetics research can contribute then isn't it clear that this type of research is close to useless.

Ritalin didn't work for me.
Dexedrine did (but only for a couple of years).

Who needs a lab test - just try 'em and see ?

APSJ
03-30-13, 01:53 PM
If this is the best genetics research can contribute then isn't it clear that this type of research is close to useless.

Ritalin didn't work for me.
Dexedrine did.

Who needs a lab test - just try 'em and see ?


That's a fair point, assuming this was the extent of the potential benefit to understanding the genetics. However, given that it would seem we're just beginning to gain an understanding, and already have some potential benefits on the horizon, why would we assume the benefits would stop there?

SB_UK
03-30-13, 01:58 PM
Is the point of disagreement ...

Point of disagreement.

Scenario 1. High heritability score was taken (in the early days of genetics) to mean that a condition was genetic.
Scenario 2. Later discovered that an epigenetic condition in a given environment mimics a purely genetic condition and provides a high heritability score.
3. Much money poured into finding the genes (Scenario 1) underlying ADHD with no genes being found.
4. Natural conclusion - to accept that the high heritability score was due to an epigenetical quality environmental interaction (Scenario 2).

Problem is though that - this means that the pharmaceutical corporation/classical medical/genetics research communities (the organizations with all the power and money in medicine) are barking up the wrong tree
- and that intervention is required in a 'place' where the pharmaceutical corporation / geneticist / medical practitioner doling out medication cannot make a difference

- in environmental change.

-*-

Trying to be as clear as possible.

The point of disagreement is that the Null hypothesis (Scenario 1) is rejected - but instead of moving on
- the scientific community has decided that they just hadn't looked hard enough - and so tried again.
And Scenario 1 was rejected yet again.
They then changed from linkage to association analysis.
Scenario 1 rejected.
Higher density mapping - Scenario 1 rejected.
Higher numbers - Scenario 1 rejected.

Approaching whole genome sequencing of probands ... ... ... as we speak.

The problem is - is that when the null hypothesis is rejected - the basic scientific method isn't to keep on repeating the same basic experiment over and over again until it isn't rejected.

At some point the other (epigenetics x environmental) basis for a high heritability score need be addressed
- but it isn't being
... ... because 'the money' does not want that possibility examined.

There's no profit in Scenario 2 being held correct to the power players of medicine.

Abi
03-30-13, 02:14 PM
At some point the other (epigenetics x environmental) basis for a high heritability score need be addressed
- but it isn't being
... ... because 'the money' does not want that possibility examined.

1} As has been stated before, there is no epigenetics without genetics, and a significant proportion of epigenetic factors are heritable...

2} If "environmental" factors (apart from extreme things like TBI and heavy metal poisoning - things like your childhood "stress" and glucose consumption or whatever) are of SIGNIFICANT importance in the aetiology of ADHD, why
{1} are the heritability stats for ADHD so high?
{2} why does ADHD affect children and adults across racial, gender, socio-economic, etc lines?
{3} why are there no studies showing statistically significant correlations between SPECIFIC "environmental factors" and the development of ADHD?

Dizfriz
03-30-13, 02:27 PM
Just for the record, here are some of the genes associated with ADHD: D




This is the first time I have tried to add an attachment:

Not quite what I wanted but it will do.


Dizfriz

Abi
03-30-13, 02:36 PM
Attachment from above:

http://www.addforums.com/forums/attachment.php?attachmentid=2070&d=1364667928

mildadhd
03-30-13, 02:38 PM
Just for the record, here are some of the genes associated with ADHD: D




This is the first time I have tried to add an attachment:

Not quite what I wanted but it will do.


Attached Images
genes.jpg (82.4 KB, 0 views)

Dizfriz


Dizfriz,

Do you have information about environmental influences in the expression of these genes?

Or other information that would help explain how these genes are being expressed?

(I didn't want to ask this question, but since you left it out, I thought I better ask)

Abi
03-30-13, 02:51 PM
I love google.

https://www.google.com/search?q=Environmental+Influences+in+the+Expressio n+of+ADHD+related+genes&rls=com.microsoft:en-US&ie=UTF-8&oe=UTF-8&startIndex=&startPage=1

Dizfriz
03-30-13, 02:58 PM
Dizfriz,

Do you have information about environmental influences in the expression of these genes?

Or other information that would help explain how these genes are being expressed?

(I didn't want to ask this question, but since you left it out, I thought I better ask)
I might suggest that you sign up for the course. It has tests but no one has to take them unless you want credit of some kind and I don't intend to take any. You seem to like watching videos so it might prove useful for you. Can't hurt.

Dizfriz

SB_UK
03-30-13, 03:01 PM
1} As has been stated before, there is no epigenetics without genetics, and a significant proportion of epigenetic factors are heritable...

2} If "environmental" factors (apart from extreme things like TBI and heavy metal poisoning - things like your childhood "stress" and glucose consumption or whatever) are of SIGNIFICANT importance in the aetiology of ADHD, why
{1} are the heritability stats for ADHD so high?
{2} why does ADHD affect children and adults across racial, gender, socio-economic, etc lines?
{3} why are there no studies showing statistically significant correlations between SPECIFIC "environmental factors" and the development of ADHD?

But there's no genetics without subatomic particles ... ... should we be studying physics to understand ADHD ?

{1}But the paper referenced above on missing heritability explains that.
{2}Because the epigenetically defined character represents the selection/emergence of a new metabolic type (reduced energy usage) - the minor changes from race to race aren't really of a concern to the major survival advantage being selected for and emerging at this point in history.
We're looking at a shift which is so strongly evolutionarily selected - that it's occurring simultaneously across the species.
{3}Stress is a convergent process - so for instance whether you're stressed from studying for an exam, being chained to an elephant or having one's toes lopped off - the same basic biological response is elicited
- thereby diluting the effect of any given 'specific' environmental stressor
- at least, beyond formal assessment.

SB_UK
03-30-13, 03:04 PM
Attachment from above:

http://www.addforums.com/forums/attachment.php?attachmentid=2070&d=1364667928


First pubmed hit for "replicated candidate genes ADHD"

DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families. (http://www.ncbi.nlm.nih.gov/pubmed/14699430)

(I was searching for replicated not failed markers)

mildadhd
03-30-13, 03:04 PM
I might suggest that you sign up for the course. It has tests but no one has to take them unless you want credit of some kind and I don't intend to take any. You seem to like watching videos so it might prove useful for you. Can't hurt.

Dizfriz

Do you have the link?

Abi
03-30-13, 03:12 PM
But there's no genetics without subatomic particles ... ... should we be studying physics to understand ADHD ?

Umm.. no comment. Really.

{1}But the paper referenced above on missing heritability explains that.

Ok will read.

{2}Because the epigenetically defined character represents the selection/emergence of a new metabolic type (reduced energy usage) - the minor changes from race to race aren't really of a concern to the major survival advantage being selected for and emerging at this point in history.
We're looking at a shift which is so strongly evolutionarily selected - that it's occurring simultaneously across the species.


What exactly are you suggesting here? That ADHD represents the "emergence" of evolutionary progress towards a ketogenic diet? :confused:

{3}Stress is a convergent process - so for instance whether you're stressed from studying for an exam, being chained to an elephant or having one's toes lopped off - the same basic biological response is elicited
- thereby diluting the effect of any given 'specific' environmental stressor
- at least, beyond formal assessment.

What's the average age of emergence of ADHD symptoms? 4? 5?
What "stress" did these little kids experience to trigger their ADHD?

SB_UK
03-30-13, 03:41 PM
What exactly are you suggesting here? That ADHD represents the "emergence" of evolutionary progress towards a ketogenic diet? :confused:

Aerobic metabolism.
Mitochondrial supremacy !

What's the average age of emergence of ADHD symptoms? 4? 5?
What "stress" did these little kids experience to trigger their ADHD?Parental stress (Peripheral's much better on this subject than I am).

The plain stress of existence (perhaps timed to the human population growth curve) as food/money becomes scarce - is the commonality
- which can't be assessed - because it's ubiquitous.

To be assessed we'd need populations which're sufficiently divorced from money - and any such populations (there will be a few) will be so different so as to make any firm conclusions.

Splurging out the idea in one line ... ....

So - suggesting timing of the emergence of ADHD to the human population growth curve - perhaps based around limiting food availability (kinda' like the ideas of Malthus) - stress based evolutionary selection for more efficient metabolism ... operational at epigeretic level ... ... invoking a switch to ketosis - ideal biochemical environment for the mitochondria - lowered/altered caloric requirements in ADDer.
Stress sensitivity (metabolically) triggered from elegant physiological to pathological under unmanageable stress.

Solution - eliminate chronic psych. stress to eliminate disorder component of ADHD.
The more efficient metabolic profile will (of course - as an evolutionarily selected condition) remain.

Barliman, Aron, Peripheral and Mate have all made the connection between ADDer and 'sensitivity'.
All there's to add is that that sensitivity is metabolic/hormonal in nature.
And physiological sensitivity is terribly easy to shift into pathological over-sensitivity in the 'wrong' environment.

That's all there is to it - high heritabilities accounted for and a reasonable rationale for not just ADHD - but all of the very many complex disorders which plague us currently - with similarly high heritabilities and no 'smoking gun' genes evident underlying causation.

Amtram
03-30-13, 04:18 PM
If you don't know the gene, and you don't know what it does, then you have absolutely no way of discovering or measuring epigenetic change. You have to know what the gene is supposed to do first before you can determine whether it's doing it exactly as planned, or whether something's going wrong.

All those genes in the list Dizfriz provided do things. Their presence alone is a starting point. Once you know that they are common among people with a condition (ADHD in this case) and not in other people, or they appear in different places in the DNA among people with a condition than they do in people without it, or they're adjacent to or overlapping other genes in people with the condition and not in people without it, then you can say you have a reason to look at them.

You look at them by breeding lab animals to have the gene, and see what the lab animals have in common with the humans. You try to alter the genes or influence how they're expressed in the animals to gather some more evidence about what the genes do, and whether they're susceptible to epigenetic change, and what factors induce that change. That way, you discover more about what they do, and whether their expression is subject to change, what makes that expression change, how to know when it's been expressed normally or abnormally.

The alternative is not knowing and not being able to do anything. Not just about the thing you started looking for, either, but everything else that might be connected. The alternative is wild guesses and stabs in the dark and what we have now is the best we ever get.

Tyler Durden
03-30-13, 04:28 PM
I repeat.

What has identifying these genes associated with adhd actually achieved?

What could it realistically achieve?

Simple question really,

Someone? Anyone?

Dizfriz
03-30-13, 04:30 PM
Do you have the link?
Sure,

https://www.coursera.org/course/adhd

Dizfriz

APSJ
03-30-13, 05:05 PM
Point of disagreement.

Scenario 1. High heritability score was taken (in the early days of genetics) to mean that a condition was genetic.
Scenario 2. Later discovered that an epigenetic condition in a given environment mimics a purely genetic condition and provides a high heritability score.
3. Much money poured into finding the genes (Scenario 1) underlying ADHD with no genes being found.
4. Natural conclusion - to accept that the high heritability score was due to an epigenetical quality environmental interaction (Scenario 2).

Problem is though that - this means that the pharmaceutical corporation/classical medical/genetics research communities (the organizations with all the power and money in medicine) are barking up the wrong tree
- and that intervention is required in a 'place' where the pharmaceutical corporation / geneticist / medical practitioner doling out medication cannot make a difference

- in environmental change.

-*-

Trying to be as clear as possible.

The point of disagreement is that the Null hypothesis (Scenario 1) is rejected - but instead of moving on
- the scientific community has decided that they just hadn't looked hard enough - and so tried again.
And Scenario 1 was rejected yet again.
They then changed from linkage to association analysis.
Scenario 1 rejected.
Higher density mapping - Scenario 1 rejected.
Higher numbers - Scenario 1 rejected.

Is epigenetic, then, synonymous with environmental? My sense of it was that it referred to something more specific, like, the way that specific genes can express in different ways. Thus, to be able to look usefully at epigenetic causes of something, you'd have to know the genes involved.

Is that not correct? Is epigenetics just a way of saying "not genetic" Like, if someone dies because they are poisoned, is that due to epigenetics? If this is the case, it seems strange that epigenetic causes *would* mirror genetic causes as you describe.

With regard to non-genetic causes generally, and again, I'm basing this on what I happen across and haven't done any surveys, but it doesn't seem to be the case that people are looking at genetic causes to the exclusion of all else. I actually see more articles about studies of links to ADHD or ADHD symptoms with environmental causes, such as sugar, or artificial coloring, or most recently, sunlight.

I'm also a bit confused by the link between medication and genetics. It would seem to me that research into genetics offers the possibility of revealing new treatments for people who don't respond to medication, or alternatives for those who do. Medication, as I understand it, isn't something that's used because of genetics, but rather because it's effective in treating the symptoms. I'm actually not familiar with any current treatment for ADHD that's based on an understanding of its causes, genetic, epigenetic, or environmental.


I repeat.

What has identifying these genes associated with adhd actually achieved?

What could it realistically achieve?

Simple question really,

Someone? Anyone?

I haven't really seen it asserted that research into the genetic causes of ADHD has had any direct effect on treatment yet, but a number of significant benefits have been suggested as realistic possibilities for the future.

Also, as stated, I haven't seen any concrete progress stemming from research into non-genetic causes either. It seems like there's a new tenuous link found to some environmental thing every few months, which then fails to be substantiated later. Basically one step forward two steps back, whereas my sense of the genetic research is that it has been progressing steadily forward.

Is that not the case?

Amtram
03-30-13, 07:44 PM
Helpful links about epigenetics (http://www.alisonblogs.com/wordpress/index.php/2013/02/13/epigenetics-links/). There will be updates in the near future.

Epigenetic does not mean environmental. Epigenetics is the means by which gene instructions from DNA are translated by RNA, sent out as messages by histones to the proteins that build the cells of an organism. The most important phase of this is prenatally, as the organism goes from being a couple of cells to a being that can live outside of the womb (or egg, as it were.) It slows down after birth and creates the cells that are needed in order for the body to grow, triggers the release of hormones that start sexual maturity and its secondary characteristics, and replaces cells that die off naturally (a process called apoptosis.)

Where environment comes into play, what it does is disrupt the epigenetic process, causing the histone signals to be changed, and making the proteins create abnormal cells. A good example of this is certain cancers, in which the genetic predisposition might be there, but it takes either a chemical exposure to activate the process, or normal aging causes imperfect cell replacement. But for the most part, epigenetics does only what it's supposed to do - make cells according to the genetic instructions in the DNA, whether they are new or replacement - and the only way environment has been demonstrated to change genetic expression so far has been to act along with susceptible genes, when introduced at the right time, and to the right point of origin in the body.

So, again, you can't argue epigenetics without understanding genetics, because the epigenetic processes that are susceptible to disruption are specific to certain genes, the environmental factors that can affect those susceptible epigenetic processes are limited, and the timing of that interference is often a specific window outside of which there will be no change.

When you think of the sheer number of possible arrangements of DNA, times the number of different things that could change how the histones instruct cell-building proteins, times the number of different ways that effect could influence gene expression depending on when it happens during a human lifespan, it's far from a simple cause and effect situation. Compared to the complexity of finding an epigenetic correlation for something, tracking down the genetic root is third grade material.

To even begin to figure it out, you absolutely must find out what the gene is telling the proteins to do - because you can take a Hox 6 protein and make it do all kinds of things, like growing eyes on the backs of fruit flies and ears on the sides of mice. If you don't know what the gene is telling that protein to do, you don't know whether it's doing what it's supposed to or not.

Tyler Durden
03-30-13, 08:11 PM
Even if that was the whole picture, so what?

Genes related to adhd have been identified, there have been no actual consequences.

Even a best case scenario creates more problems than it solves.

Whether it can have any impact at all on adhd in the real world is all speculation.

This is a theoretical/hypothetical discussion, none of this exists in relation to adhd, or any similar disorder, so why is it in the scientific and not theoretical section?

Lunacie
03-30-13, 08:19 PM
Even if that was the whole picture, so what?

Genes related to adhd have been identified there have been no consequences.

Even a best case scenario creates more problems than it solves.

Whether it can have any impact at all on adhd in the real world is all speculation.

This is a theoretical/hypothetical discussion, none of this exists in relation to adhd, or any similar disorder, so why is it in the scientific section?

Scientific knowledge begins with theories and hypotheses, no? :doh:

Abi
03-30-13, 08:25 PM
Scientific knowledge begins with theories and hypotheses, no? :doh:

That's one door you DON'T want to open.

Lunacie
03-30-13, 08:45 PM
That's one door you DON'T want to open.

What? What do you mean? :confused:

Amtram
03-30-13, 09:03 PM
Some genes have been identified. I suppose you haven't been paying attention to the details in this thread, which have outlined pretty clearly that finding the genes is part of the solution, and that there are lots of other steps, right?

Nonetheless, we have tons of examples of conditions that have been identified by their genetic origins, and have been effectively treated because of that. The story in the OP is only one. No evidence that any of these have created more problems than they solved. Real world impact.

Just this week, researchers announced that they've identified a gene that causes prostate cancer, and are testing genetic therapy that so far seems to be effective in curing it. They've also developed a gene therapy for diabetes that is finishing up successful testing in dogs, gene therapy for color blindness, hemophilia B, epilepsy, and malignant gliomas are going through human testing right now. One can only imagine the horrible problems that will be caused by treating and curing things like these! And yes, they are happening in the real world.

It's not even all that difficult to find these examples - you don't need to work in the field or subscribe to professional journals or anything. On the other hand, it takes a great deal of concerted effort not only to be completely unaware of these real world examples, but to assert that they don't exist when they're easily accessible all over the internet. And looking at them on a timeline, where you can see the breakthroughs coming faster and faster, more research every year making in through human trials, more complex conditions being worked on each time, it's completely irrational to claim that they in no way indicate that progress has been made and will continue to be made in the areas of genetic research.

If your frame of reference is things that happen in the real world, then claiming that none of these things is of any current or potential value would require a complete redefinition of what the real world is. In the real world that the rest of us live in, genetic research is leading to knowledge, technical advances, and life-saving treatments every day. In the real world, that kind of success usually indicates that predicting even more of the same is a perfectly reasonable, rational assumption.

This (http://www.michaelhanscom.com/eclecticism/graphics/2003/07/graphics/lalalala.gif) does not make things stop happening.

Amtram
03-30-13, 09:07 PM
Scientific knowledge begins with theories and hypotheses, no? :doh:

Actually, it begins with observation, experimentation, then hypotheses. (Then more observation, experimentation and hypotheses, ad nauseam, or until the funding dries up!) If things go right, then you end with facts, Theories, and Laws.

Tyler Durden
03-30-13, 09:09 PM
This is all hypothetical/theoretical, you do understand that right?

No actual benefits/"up sides" exist in relation to adhd or similar non monogenic disorders.

If they ever will is speculation.

You have had plenty of opportunities to identify actual realised upsides in relation to adhd as I have asked many times over the last 134 posts.

This is a theoretical/hypothetical thread. And so belongs in that section. Do you understand what I am saying?

Lunacie
03-30-13, 09:21 PM
Actually, it begins with observation, experimentation, then hypotheses. (Then more observation, experimentation and hypotheses, ad nauseam, or until the funding dries up!) If things go right, then you end with facts, Theories, and Laws.

Okay, observation comes before hypotheses,
then comes testing and experimentation,
and all of that comes before scientific knowledge*, yes?

*scientific knowledge - aka - facts, theories, laws

Lunacie
03-30-13, 09:29 PM
This is all hypothetical/theoretical, you do understand that right?

No actual benefits/"up sides" exist in relation to adhd or similar non monogenic disorders.

If they ever will is speculation.

You have had plenty of opportunities to identify actual realised upsides in relation to adhd as I have asked many times over the last 134 posts.

This is a theoretical/hypothetical thread. And so belongs in that section. Do you understand what I am saying?

If you think it should be moved, send a message to the mods.

However, according to the headers on both these sections, since this
thread isn't specifically about ADHD it would seem to fit better in the
Scientific Discussion section.



Theoretical & Philosophical Discussion (http://www.addforums.com/forums/forumdisplay.php?f=336)
This forum is for new, unconventional, or untested ways of thinking about ADHD that challenge current thinking, and welcoming posts in any format


Scientific Discussion (http://www.addforums.com/forums/forumdisplay.php?f=337)
This forum is for discussions tied to published/presented scientific research, in a quasi-academic format, with references where appropriate

APSJ
03-31-13, 11:33 AM
This is all hypothetical/theoretical, you do understand that right?

No actual benefits/"up sides" exist in relation to adhd or similar non monogenic disorders.

If they ever will is speculation.

You have had plenty of opportunities to identify actual realised upsides in relation to adhd as I have asked many times over the last 134 posts.

This is a theoretical/hypothetical thread. And so belongs in that section. Do you understand what I am saying?

This is what I was trying to clarify in my earlier post. It doesn't seem, then, that there's any disagreement on the point that there are currently no ADHD treatments based on genetic research.

So, the disagreement then is whether the various benefits proposed as possible/probable in the future due to genetic research really *are* possible or probable because ADHD is not a monogenic disorder?

That leads to a few of clear questions then:

1. What about the concrete benefit Dizfriz cited for medication selection? Is there reason to believe the progress toward that is illusory?

2. Is there reason to believe that research into environmental or epigenetic causes is more promising? What benefits have been realized concretely from such research?

3. For epigenetics, is there any argument that, contrary to Amtram's assertion, we *can* research these causes *without* first gaining a better understanding of the genetic causes?

4. SB noted that the benefit cited by Dizfriz isn't terribly significant given that we can select medication through trial and error. Is the argument then that medication is an effective enough treatment that we don't need to know the causes? While I've been taking medication for twenty years, and it works, it's awfully inconvenient and has side effects. If research into genetics can yield alternatives, the possible benefits do seem worthwhile to me.

Amtram
03-31-13, 11:53 AM
And since this thread started off with an example of successful clinical trials based entirely on knowledge acquired from peer-reviewed published research, and everything we know about genetics and epigenetics was acquired by scientific testing that has been peer-reviewed, published, and reproduced, we are no longer dealing with genetics or epigenetics as hypotheticals - we are able to develop and test new hypotheses based on solid evidence, and perform experimentation that supports or disproves these hypotheses using well-established scientific protocols.

someothertime
03-31-13, 12:00 PM
Scope for environmental cause studies is too broad without cherry-picking a pre-disposed target group with the help of sequencing.

Tyler Durden
03-31-13, 12:13 PM
So everyone agrees this is hypothetical and there is nothing to confirm any of this will ever result in a real impact on adhd.

It is not about environment or genetics, it has not been a valid argument for a long time, it has always been both, it is about there having been no real up side to identifying adhd genes, and believing they ever will is at best speculative.

Amtram
03-31-13, 12:15 PM
This is why we need fruit flies and rats and mice. I don't mind so much about the fruit flies, but I feel kind of bad for the rats and mice. It's a necessary evil, though.

Tyler Durden
03-31-13, 01:18 PM
How is that useful or relevant?

Because fruit flies tend to benefit more from adhd than rats and mice?