Brains, Genes And Chemical Imbalances

Oh my this one got the commentators responding!

Studies of mental functions, behaviors and the nervous system.

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Re: Brains, Genes And Chemical Imbalances

#61  Postby Federico » Jul 24, 2014 1:45 pm

As a further and more recent example of how important is Nature in the development of schizophrenia I'll quote an article written for Medical News Today and titled: "Researchers identify more than 80 new genes linked to schizophrenia."

Quote:

".... Prof. O'Donovan and fellow researchers from the Schizophrenia Working Group of the Psychiatric Genomics Consortium - an international collaboration of more than 300 scientists set up in 2007 to conduct large-scale research into psychiatric disorders - uncovered an array of genetic risk factors for schizophrenia, shedding light on the condition's biological cause.

To reach their findings, the researchers analyzed 36,989 genetic samples from people with schizophrenia, alongside genetic samples from 113,075 healthy individuals.

The analysis - results of which are published in the journal Nature - revealed 108 specific locations in the human genome linked to schizophrenia. Of these, 83 had not been previously associated with the condition.

The team found that many of these genes were expressed in brain tissue, some of which are related to the functioning of neurons and synapses - responsible for the electrical and chemical signaling between neurons. Furthermore, the team also found that some of the genes were expressed in the immune system, supporting previous theories that schizophrenia is associated with immunological mechanisms.
"

One of the most interesting finding made by Prof.O'Donovan and coll. is that a dopaminergic receptor named DRD2 is linked to schizophrenia, while it's well known that many schizophrenia drugs exert their effects through brain dopaminergic pathways.

In addition, Prof. O'Donovan emphasizes the fact that genetics provides only a marker of biological events taking place in the brain of normal and of mentally affected individuals, but may also open up new understanding of the disease causality and new therapeutic approaches.
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Re: Brains, Genes And Chemical Imbalances

#62  Postby epepke » Jul 24, 2014 6:45 pm

Asta666 wrote:I don't think that only the psychoanalytic culture was worried about designing treatments according to the individual patient.


Clearly not only the psychoanalytic culture; that is an example, and I think the most common and most notably one. Therefore fairly obvious as an example. At least it involved listening to the patient and also staying out of the patient's personal space while listening, which is a very interesting idea. At least it recognizes how easy it is for a therapist, without being aware of it, to drive the process in ways that are not guaranteed to be appropriate.

Psychoanalysis is also the subject of a great deal of popular culture, and there are sometimes great insights about social relationships in what is said through popular culture. MAD Magazine before Bill Gaines died had quite a lot of great stuff that is only now becoming understood by Cognitive Science.

Contract with the individual versus contract with society is huge and is far from limited to psychiatry, but this isn't a thread on all cultural practices. If it were, it would be a lot longer, and people would probably have to spend years reading it.

The behaviour analytic one too (see for a review of some of these issues from that pov http://www.ncbi.nlm.nih.gov/pubmed/22477707) and also practically all the psychotherapy trends I know of.
I think that sorting people into categories might be mainly useful for administrative purposes like counting how many people need insurance and the like, for constituting groups for research and not so much for determining treatment (at least not for psychotherapy).


Might be. Might. What I am saying here is that there is a difference between intent and effect. It's one thing to say that you are going to do something and quite another actually to do it in practice.

Thanks for the link. I'll look at it.

That is certainly a valid concern, but given also the much more limited role syndromes can also take suggests to me that whether this is happening or not has to be assessed in more specific terms. (btw sorry for meddling in)


I quite like it. However, it would be interesting to me if you could expand on "the much more limited role syndromes can also take." There are many potentially interesting things to discuss. I could list them, but I don't want to prejudice the discussion. Instead, perhaps laconically, what I will call in a meta-sense "the role of the role." How is the role constructed, to use some trendy critical lingo? What purpose does it serve, and whose purpose is that?
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Re: Brains, Genes And Chemical Imbalances

#63  Postby Arjan Dirkse » Jul 25, 2014 10:30 pm

I think there is an evolutionary and educational factor at play in assigning blame and feeling guilt and responsibility- and accordingly, developing a sense of free will. In an admittedly simplistic example: say if a little toddler goes around the house breaking vases and eating the goldfish and smearing his poop on the walls, his parents will tell him not to do it, and little Johnny will realize he has a choice between "right" and "wrong". However if those parents think "well it's his damned faulty neurons telling him to eat the goldfish, it's not our place to tell him not to", that turns into a self fulfilling prophecy. The kid won't be responsible for it, because he never learnt, and grows into a no good hoodlum who deserves at least the consideration he isn't fully responsible because he wasn't raised right.

So it's an illusion in a way, but an illusion that is necessary. The kid having "free will" to pick right over wrong is really just reacting to stimuli he learnt somewhere in life. Although we behave mechanistically, free will being a form of behavior picking the "right" choice over the wrong in accordance with genes and environment, the ability to judge one's own actions is important.

Of course often we have to weigh certain factors against each other; very often, the drive for instantaneous gratification against the exhortation to do what we might be able to realize is the proper thing to do. In this moment, the illusion of free will is important to weigh the two. To think through how these two compare. "Free will" is how we build order and coherence in our societies, in a way.
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Re: Brains, Genes And Chemical Imbalances

#64  Postby epepke » Jul 25, 2014 10:48 pm

Arjan Dirkse wrote:I think there is an evolutionary and educational factor at play in assigning blame and feeling guilt and responsibility- and accordingly, developing a sense of free will. In an admittedly simplistic example: say if a little toddler goes around the house breaking vases and eating the goldfish and smearing his poop on the walls, his parents will tell him not to do it, and little Johnny will realize he has a choice between "right" and "wrong". However if those parents think "well it's his damned faulty neurons telling him to eat the goldfish, it's not our place to tell him not to", that turns into a self fulfilling prophecy. The kid won't be responsible for it, because he never learnt, and grows into a no good hoodlum who deserves at least the consideration he isn't fully responsible because he wasn't raised right.

So it's an illusion in a way, but an illusion that is necessary. The kid having "free will" to pick right over wrong is really just reacting to stimuli he learnt somewhere in life. Although we behave mechanistically, free will being a form of behavior picking the "right" choice over the wrong in accordance with genes and environment, the ability to judge one's own actions is important.


Well stated with appropriate snark and quite accurate.

The problem comes when this imperative, which may, as you point out, have been selected for by evolution, gets in the way of a better understanding.

I mean, we didn't evolve to take antibiotics or perform surgery or wash our hands before surgery or even take a break from eating each other's feces, so it's all natural, right? It's necessary to jump in the shit after the compound fracture with the bone sticking out.

Well, maybe there isn't. Maybe there's something else that works better. Maybe it's the same with brains as it is bones (might not be the same thing, but it might be the same in that there's something that works better).

Of course often we have to weigh certain factors against each other; very often, the drive for instantaneous gratification against the exhortation to do what we might be able to realize is the proper thing to do. In this moment, the illusion of free will is important to weigh the two. To think through how these two compare. "Free will" is how we build order and coherence in our societies, in a way.


I've been saying this about free will for decades. It's a completely incoherent concept. All that is necessary is that people behave as if they had free will, and even then, it's only a mind hack.

I think this is a bit more honest than Dan Dennett, who spends a lot of claptrap arguing that free will exists, and then when you're about ready to hurl your shit at the guy (because it's obvious that he isn't even trying), he dismissed the actual existence of free with with a wave of his hand, declaring that nobody cares about it. Slimy behavior.
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Re: Brains, Genes And Chemical Imbalances

#65  Postby Templeton » Jul 26, 2014 1:11 am

:popcorn:

How many people show genetic markers for schizophrenia and do not develop the disorder?

Genes express according to internal and external environmental influences.

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Re: Brains, Genes And Chemical Imbalances

#66  Postby epepke » Jul 26, 2014 3:26 am

Templeton wrote::popcorn:

How many people show genetic markers for schizophrenia and do not develop the disorder?


Great question. I don't know if there's an answer.

This is a bit old but fairly popular, and it doesn't seem to me to indicate that the story is very good.

http://www.ncbi.nlm.nih.gov/pubmed/3516863

This is more recent but pretty limited.

http://www.sciencedaily.com/releases/20 ... 172951.htm

This isn't a paper, but it's very recent, and it doesn't look all that hopeful.

http://www.cnn.com/2014/07/22/health/sc ... nia-genes/

It kind of feels as if one doesn't really have to go the "developmental adaptation" route until the "we really want there to be a genetic marker" route has been explored.
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Re: Brains, Genes And Chemical Imbalances

#67  Postby Asta666 » Jul 26, 2014 4:36 pm

epepke wrote:Clearly not only the psychoanalytic culture; that is an example, and I think the most common and most notably one. Therefore fairly obvious as an example.

OK.

epepke wrote:Might be. Might. What I am saying here is that there is a difference between intent and effect. It's one thing to say that you are going to do something and quite another actually to do it in practice.

Regarding behaviour analysis I think it certainly is the case in practice, since you necessarily need to go beyond the data from the psychiatric diagnosis and gather data specific to the individual in question, for instance in order to perform a functional assessment, which is what actually determines the treatment plan.

epepke wrote:Thanks for the link. I'll look at it.

You're welcome.

epepke wrote:However, it would be interesting to me if you could expand on "the much more limited role syndromes can also take." There are many potentially interesting things to discuss. I could list them, but I don't want to prejudice the discussion. Instead, perhaps laconically, what I will call in a meta-sense "the role of the role." How is the role constructed, to use some trendy critical lingo? What purpose does it serve, and whose purpose is that?

Basically, the limited role is using the syndromes for research and administrative purposes between professionals when required more than to determine treatment plan and being the reason that is given to the person regarding the cause of his problems. From the psychotherapy pov anyway I don't see any other way around it, but even from the biological psychiatry pov, no matter how much faith federico and kennyc have in it, even some of the most authoritative advocates of the trend that looks for biogenetic causes (the American APA and NIMH) have not long ago recognized that there is not enough evidence to even base diagnosis on this kind of variables, let alone "explain" them (http://blogs.discovermagazine.com/neuro ... formation/ for the references).

epepke wrote:
Of course often we have to weigh certain factors against each other; very often, the drive for instantaneous gratification against the exhortation to do what we might be able to realize is the proper thing to do. In this moment, the illusion of free will is important to weigh the two. To think through how these two compare. "Free will" is how we build order and coherence in our societies, in a way.


I've been saying this about free will for decades. It's a completely incoherent concept. All that is necessary is that people behave as if they had free will, and even then, it's only a mind hack.

Oh but you don't know about quantum fluctuations :roll: .
The behavioral account sets the task for the physiologist. Mentalism on the other hand has done a great disservice by leading physiologists on false trails in search of the neural correlates of images, memories, consciousness, and so on. Skinner
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Re: Brains, Genes And Chemical Imbalances

#68  Postby LucidFlight » Jul 26, 2014 4:39 pm

Did somebody say quantum fluctuations? I love those things!
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Re: Brains, Genes And Chemical Imbalances

#69  Postby epepke » Jul 26, 2014 9:11 pm

Asta666 wrote:Basically, the limited role is using the syndromes for research and administrative purposes between professionals when required more than to determine treatment plan and being the reason that is given to the person regarding the cause of his problems. From the psychotherapy pov anyway I don't see any other way around it, but even from the biological psychiatry pov, no matter how much faith federico and kennyc have in it, even some of the most authoritative advocates of the trend that looks for biogenetic causes (the American APA and NIMH) have not long ago recognized that there is not enough evidence to even base diagnosis on this kind of variables, let alone "explain" them (http://blogs.discovermagazine.com/neuro ... formation/ for the references).


There may not be another way around it, but there's a difference between using something that works based on an estimation that it works and supposing some mysterious deep reason that makes it all logical.

While we're trading links, here's one. I asked my excellent friend, Farhat Habib, who is a geneticist, if he was good at markers for schizophrenia. He wasn't in particular, but this is food for thought:

http://www.plosmedicine.org/article/inf ... ed.0020124

As for quantum fluctuations, I know them far too well to get all woo about them.
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Re: Brains, Genes And Chemical Imbalances

#70  Postby DavidMcC » Jul 30, 2014 12:17 pm

Arjan Dirkse wrote:...
So it's an illusion in a way, but an illusion that is necessary. The kid having "free will" to pick right over wrong is really just reacting to stimuli he learnt somewhere in life. Although we behave mechanistically, free will being a form of behavior picking the "right" choice over the wrong in accordance with genes and environment, the ability to judge one's own actions is important.

Of course often we have to weigh certain factors against each other; very often, the drive for instantaneous gratification against the exhortation to do what we might be able to realize is the proper thing to do. In this moment, the illusion of free will is important to weigh the two. To think through how these two compare. "Free will" is how we build order and coherence in our societies, in a way.

A. What is a "learnt stimulus"?
B. I take it that you are using the term, "free will" in the traditionally idiotic way (which is defined to be physically impossible, and is therefore one of the most useless phrases in the English language).
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Re: Brains, Genes And Chemical Imbalances

#71  Postby Darwinsbulldog » Jul 31, 2014 2:20 am

There are about 108 genes associated with the risk of developing schizophrenia [misplaced paper, 2014], and many of these gene candidates overlap for other conditions like bipolar. Clearly, there are also environmental influences at work. eg:-

Cross-Disorder Group of the Psychiatric Genomics, C. (2013). "Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs." Nat Genet 45(9): 984-994.
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17–29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

http://dx.doi.org/10.1038/ng.2711

Petrovsky, N., et al. (2014). "Sleep Deprivation Disrupts Prepulse Inhibition and Induces Psychosis-Like Symptoms in Healthy Humans." The Journal of Neuroscience 34(27): 9134-9140.

Translational biomarkers, such as prepulse inhibition (PPI) of the acoustic startle response, are playing an increasingly important role in the development of antipsychotic drugs for schizophrenia and related conditions. However, attempts to reliably induce a PPI deficit by psychotomimetic drugs have not been successful, leaving an unmet need for a cross-species psychosis model sensitive to this widely studied surrogate treatment target. Sleep deprivation (SD) might be such a model as it has previously been shown to induce PPI deficits in rats, which could be selectively prevented with antipsychotic but not anxiolytic or antidepressant compounds. Here, in a first proof-of-concept study we tested whether SD induces a deficit in PPI and an increase in psychosis-like symptoms in healthy humans. In two counterbalanced sessions, acoustic PPI and self-reported psychosis-like symptoms (Psychotomimetic States Inventory) were measured in 24 healthy human volunteers after a normal night's sleep and after a night of total SD. SD decreased PPI (p = 0.001) without affecting the magnitude or habituation of the startle response (all p > 0.13). SD also induced perceptual distortions, cognitive disorganization, and anhedonia (all p < 0.02). Thus, extending previous rodent work, we conclude that SD, in combination with the PPI biomarker, might be a promising translational surrogate model for psychosis as this method represents a possibility to partially and reversibly mimic the pathogenesis of psychotic states.

http://www.jneurosci.org/content/34/27/9134.abstract

The large number of genes involved [up to 108] suggests to me that psychiatric disease is often a matter of poor gene regulation rather than faulty coding genes. The fact that environment is a factor and disease running in families is strongly suggestive of mostly epigenetic rather than genetic factors.
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Re: Brains, Genes And Chemical Imbalances

#72  Postby DavidMcC » Jul 31, 2014 7:06 pm

Thanks, DBD! :thumbup:
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Re: Brains, Genes And Chemical Imbalances

#73  Postby Templeton » Jul 31, 2014 8:25 pm

Houston we have a problem...What causes genes to express?

Take a single undifferentiated cell - a stem cell, place it in a safe healthy environment, like a petri dish with an agar of nutrient balanced growth medium. In a short while the cell will replicate and after a while longer, where once we had one we now have thousands of happy, healthy, identical undifferentiated stem cells.
Now we take those happy stem cells and divide them into three separate petri dishes with new growth mediums. In one petri dish the growth medium has liver cells, in another muscle cells, and a third bone cells.
What will the genes do?
Adapt to their environment.

What happens if; after our cells,(genes) in their new petri dishes have become liver cells, muscles cells, and bones cells, we add other ingredients to their environments, say for instance, a solution of liquefied Big Mac? or maybe hand lotion, or something directly from the labs of Monsanto? What will happen to the cells?

The point being is, genes express according to their internal and external environment. The symptoms of diseases, whether mental or physical, are the result of an adaptive gene expression which is responding to the environment with which it is immersed.
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Re: Brains, Genes And Chemical Imbalances

#74  Postby Federico » Aug 01, 2014 12:34 pm

Templeton,
haven't you ever heard of Epigenetics?

This is what I wrote about 3 years ago for the thread Is Lamarkism back? (Quote):

"....The way I understand it -- but I won't bet my bippy on it -- the whole RD theory of the selfish gene is based upon the classical Darwinian evolutionary process where genes are mutated in a time frame of thousand of years and according to a scheme which would be advantageous to the individual thus to the gene itself.
The recent discovery of new mechanisms of evolution where not the gene itself is mutated but the genomic apparatus controlling gene's expression is modified by the environment within a much shorter time frame, has given new credence to Lamarkism and the possible transmission within a generation of newly acquired adaptive characteristics.

An article recently published in The NewScientist and entitled "Epigenetic clue to schizophrenia and bipolar disorder " provides new evidence for an epigenetic mode of transmission of Schizophrenia and of Bipolar disorder.

"......TWIN studies have shown that people with schizophrenia and bipolar disorder have changes in gene activity caused by their environment. The finding provides the strongest evidence yet that such gene changes might cause the conditions.
Jonathan Mill at the Institute of Psychiatry, King's College London, and colleagues scanned the genome of 22 pairs of identical twins - chosen because one twin in each pair was diagnosed with schizophrenia or bipolar disorder.

"As expected, the twins had identical DNA. However, they showed significant differences in chemical "epigenetic" markings - changes that do not alter the sequence of DNA but leave chemical marks on genes that dictate how active they are. These changes were on genes that have been linked with bipolar disorder and schizophrenia.
Mill's team scanned for differences in the attachment of chemical methyl groups at 27,000 sites in the genome. Methylation normally switches genes off, and de-methylation turns them on."

"....the most significant differences, with variations of up to 20 per cent in the amount of methylation, were in the promoter "switch" for a gene called ST6GALNAC1, which has been linked with schizophrenia. The twin scans also revealed methylation differences in GPR24, a gene previously linked to bipolar disorder."

"...... [with additional, time-linked studies] [i]It might be possible then to link the alterations to environmental changes such as stressful events or diet, which have been shown to cause inheritable epigenetic changes in mice".

"I feel this is the best evidence yet, from human studies, supporting the hypothesis that epigenetic mechanisms may drive psychiatric disorders," says David Sweatt, who studies epigenetics at the University of Alabama and was not involved in the study.

I find these data fascinating, and in some way confirmatory of what I have been writing for a while, namely that mental disorders might be caused by environment- altered genes' functions similarly to some body illnesses.
It would be interesting but difficult to realize is a study of the heritability of such pathogenetic mechanism. (End of quote)
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Re: Brains, Genes And Chemical Imbalances

#75  Postby epepke » Aug 01, 2014 2:13 pm

Templeton wrote:Houston we have a problem...What causes genes to express?

...


We all know this.

When people talk about genetic influences, they are talking about the differences that the presence or absence of a gene or what form it takes makes in the phenotype.
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Re: Brains, Genes And Chemical Imbalances

#76  Postby Templeton » Aug 01, 2014 5:04 pm

epepke wrote:
Templeton wrote:Houston we have a problem...What causes genes to express?

...


We all know this.

When people talk about genetic influences, they are talking about the differences that the presence or absence of a gene or what form it takes makes in the phenotype.


What is a gene? What do they do? Do genes make a decision?

I apologize if I sounded condescending, that was not my intent - It appears that the conversation suggests that genes create disease, and while the Central Dogma in medical science has long believed that the flow of information from the gene is one way, DNA => RNA => Proteins => that assumption is incorrect. Cells in the body receive information from our environment, both internally and externally, and the gene is only a blueprint of information used to adapt to the information received from the current environment. It does not make the decisions.
There are defective genes, (a discussion for another time) though the current estimate, off the top of my head, is that defective genes account for aprox. 2.5% of the population world wide - so roughly two hundred million people. What would be the percentages of researchers actually diagnosing that small a part of the population once or twice in a life time, and yet medical science would have us believe that defective genes are a common occurrence. The focus should be the environment...that is the common denominator in every disease. Genes express according to the information received from the environment, not the other way around, and they change expression in order for us to survive in a changing environment.
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Re: Brains, Genes And Chemical Imbalances

#77  Postby DavidMcC » Aug 03, 2014 4:00 pm

Templeton wrote:...
There are defective genes, (a discussion for another time) though the current estimate, off the top of my head, is that defective genes account for aprox. 2.5% of the population world wide - so roughly two hundred million people.
...

Actually, I suspect that nearly everyone has at least one "defective gene", because we all have two copies of every gene, but only one of them is expressed if it is recessive wrt its equivalent in the other chromosome of the pair. What shows is only the nmber who have two copies of such "defective" genes. When in single copy, they are advantageous (which is why they evolved in the first place), by, eg conferring some immunity from malaria. When in double copy, they may cause a debilitating condition, such a sickle-cell anaemia.
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Re: Brains, Genes And Chemical Imbalances

#78  Postby Templeton » Aug 03, 2014 5:23 pm

The point being is that the genes aren't in control, and therefore not the cause of mutations. Genes express according to internal and external environmental influences, and as such express in response to what we; eat or absorb and breath into the system, how we move (our physical action or inaction), and how we think.
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Re: Brains, Genes And Chemical Imbalances

#79  Postby DavidMcC » Aug 03, 2014 5:43 pm

Templeton wrote:The point being is that the genes aren't in control, and therefore not the cause of mutations.
Not in control of what, exactly? Nobody suggested that genes cause mutations, it's an absurd notion.
Genes express according to internal and external environmental influences,
...

... And in accordance with which alleles of the given gene we have, and of those that affect its expression level.
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Re: Brains, Genes And Chemical Imbalances

#80  Postby Templeton » Aug 06, 2014 10:55 pm

DavidMcC wrote:
Templeton wrote:The point being is that the genes aren't in control, and therefore not the cause of mutations.
Not in control of what, exactly? Nobody suggested that genes cause mutations, it's an absurd notion.
Genes express according to internal and external environmental influences,
...

... And in accordance with which alleles of the given gene we have, and of those that affect its expression level.


Actually it is the prevailing philosophy of medical science that suggests this.

What does the discussion above with regard to Schizophrenia and genetic markers tell you?

Furthermore how are mental diseases treated?
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