“but it does strike me as interesting.” --- Philip Dawdy

Ditto…

Warmly,
Herb
VNSdepression.com

Perhaps this finding can provide a link as to why ssri's and other drugs like Chantix induce suicide ideation in some users.

From www.SSRIstories.com comes this interesting Journal Article which explains that SSRIs may be linked to some serotonin receptors which increase the risk of suicide.

Here is the study:
http://www.nature.com/news/2006/061016/full/061016-1.html

Published online: 16 October 2006; | doi:10.1038/news061016-1

Brain changes may suggest suicide risk
Suicidal behaviour linked to serotonin receptors.

Jim Giles

Depression: a condition in its own right?
There is growing evidence that suicidal behaviour is a condition in its own right and not just a consequence of other psychiatric disorders, say brain researchers.

People who commit suicide show distinct changes in their brain that are independent of any mental illness they may be suffering from, according to studies presented on 15 October at the annual meeting of the Society for Neuroscience in Atlanta, Georgia. Such work could lead to new tests for suicide risk, say some of those behind the research.

They speculate it may also help to explain why a small minority of patients on SSRIs, a common form of anti-depressant that boosts serotonin levels, are more likely to commit suicide.

"There is an assumption that people get depressed, get depressed, get depressed....and then finally end it," says Mihran Bakalian of the New York State Psychiatric Institute. "But that is not borne out by the biochemical or psychiatric studies." Bakalian says the idea is becoming firmly established among groups such as his that study suicide, but has yet to filter down to many medical doctors.

Data from researchers such as Stella Dracheva, who is based at the Bronx Veterans Affairs Medical Center in New York, are beginning to change that.

Receptor type

Dracheva and her colleagues examined cell-surface receptors for serotonin, a substance known to be linked to depression, in the brains of 22 people who had committed suicide and 82 who had died by other means.

The serotonin receptor they studied ­ 5-HT2C ­ is unusual in that it comes in 24 different forms. Dracheva found that in one area of the dorsolateral prefrontal cortex, a brain region involved in high-level functions such as planning, one of these forms was present in higher levels in the suicide cases ­ regardless of which psychiatric condition the person had been suffering from, if any at all. Although most suicides happen among those with conditions such as bipolar disorder, depression or schizophrenia, a small number happens among people simply under stress.

Although they don't know for sure that these brain changes are a cause rather than an effect of suicide, the work suggests that some people are at higher risk of committing suicide due a difference in their brain structure or chemistry, Dracheva says.

Aggressive behaviour

Bakalian thinks that the difference is most likely to lie in the systems that modulate aggression. Psychiatric studies have frequently linked aggression with suicide, and it may be that people who take their own lives are unable to reign in aggressive urges towards themselves.

In a study also presented in Atlanta, Bakalian found that suicide victims had a lower density of serotonin receptors in their amygdala, a brain region involved in controlled aggression and other emotions, than those who died by other means.

Bakalian says that psychiatrists should be made more aware of these results. But he adds that there is little they could do at present, because there is as yet no better way to focus treatment.

Dracheva's work suggests that a test for types of serotonin receptor might be useful to identify those most at risk.

She adds that in some cases it might be better for psychiatrists not to prescribe SSRIs. Data from animals suggest that SSRIs can increase the number of serotonin receptors now linked to suicide. That could be why a small minority of patients are more likely to commit suicide once on this medication, Dracheva speculates."

Give an update when the real story, and not just the press release, appears.

This is a case-control study. You take a handful of people who have (or had) some characteristic, and compare evidence for some hypothesized causal mechanism between that handful of people and an otherwise similar group of people who do not (or did not) have the characterisitc.

The logic is that if you actually do observe the suspected difference, then that difference has sone causal connection to the characteristic.

This is a decent way to explore hypotheses, such as: some hypothesis that there is some abberant process going on in brain cells of people who died by suicide versus those who died by other means.

Decent, but not great. There are many limits to a case-control study. So, we will have to look over this paper to see how strong the methods are - the devil is in the details.

The sample size could be small - this would increase the likelihood that some random finding led to the observed difference. Have you ever been in some group where everyone joked: "Hey, didn't you get the memo - today is green shirt day?" cuz a few people in the group, but not all, happened to show up with green shirts on? That is an example of how some random, unrelated detail could get into the spotlight as being possibly meaningful / causal.

The case / control attempts to make two similar groups, limiting the various alternative explanations. This is a decent strategy. Yet, the one thing we know for sure is: these two groups are different! One group consists of suicide completers, and the other group consists of people who, as far as we know, did not die of suicide. How else do they differ? We just don't know, but we know for sure they are NOT the same.

Case/control studies often declare results in clear-cut terms, but when you look at the actual data points, there is overlap. This pattern of data works against the hypothesis. If this brain regulation phenomenon truly is involved in the path to suicide, there should be no one in the non-suicide group with the characteristic brain problem, and everyone in the suicide group with clear evidence of this problem. In some medical issues, this is the case (for example, conducting genetic analysis of people with or without Down's syndrome), but in these mental health situations, things are usually more heterogeneous. For example: we don't know the degree of suicidality of those who died from other causes; the pathology of the non-suicide group may have led to some brain function difference, rather than the suicidality leading to the aberrant brain observaton; some aspect of hospital treatment such as nutritionist-determined meals, could have led to a 'better' characteristic in the brains of those who died of causes other than suicide; etc.

There are other weaknesses of case/control, but those are a couple main ones.

So, if the study design is a good quality, then this could point to some key aspect of emotional instability that could possibly be measured in a living person who has ben bothered by suicidality.

Also, someone could evaluate whether SSRIs contribute to this phenomenon, at lest for some people, and so might account for the suicidality that seems to be associated with SSRIs.

Methylation is routinely checked by alternative care practitioners when treating for mental health issues...

there are supplements that can affect levels of methylation...

I don't know if these findings are related to what alternative care docs do or not...

but it is certainly worth looking into...

I don't think this finding is very significant. Suicide is an extremely complicated human "behavior" and has extremely low "heritability" as they call it (read: twin studies).

Methylation is involved in everything under the sun and you have to wonder what kind of chemical blitzkreig goes on in the brains of recently deceased people. Thats something these studies can never control for and is an everlasting and perrenial problem with this kind of research.

On a social note, I am roundly opposed to wasting any money or brain power on this kind of basic science research as it relates to suicide. Suicide is logically not driven by genetic factors and when people use the word "epigenetic" in this kind of research, it can mean two things: 1) We admit environment may be involved, but we will never study it and continue on with an exclusively molecular approach, or 2) Our theory that "it" is driven primarily by genetic factors just blew up in our face. (i.e. it is increasingly becoming less supportable)

Suicidal people do not need this kind of research. It adds no useful knwoledge to our base. And often, every piece of information produced by a study like this ends up in effect being dumped into a neverending abyss of research conceived on false premises -- eventually.

Very few human diseases are single allele, very few, and we know alot about them, and still they are hard to find drugs to treat. Mental illnesses are not counted among them. And since we have mapped the human genome, it is becoming increasingly clear that genetic factors count for little in mental illness. It is plausible that they count for nothing in any appreciable way. So now the psychiatric genetics field is talking about "intermediate phenotypes" to salvage their failing theories -- here we go again! Another intellectual diversion to forestall understanding human suffering and treatment another forty years -- another dead end.

It's also amusing to me that this field can't apply any amount of introspection to itself, when, for instance, the whole field of cancer is currently in upheaval ( or soon will be completely), because the mutation theory of cancer is quickly losing ground. Cancer is not primarily driven by genes and has mostly complex environmental causes. If we can't get something like cancer right. What makes us think there will be a genetic basis to complex human behvaiors. I don't know, but it would be a good question to ask the editors of Biological Psychology.

B-i-o-l-o-g-i-c-a-l P-s-y-c-h-l-o-g-y... think about it.

July's issue of Nature reported on this extensively, but of course drew the wrong conclusions.

If anyone would like to read serious work that supports these ideas they can read anything by Richard Lewontin. He's an awesome guy.

This kind of research, (reported in Biological Psychology) is like academic masturbation. The beneift is singular.

I've been researching epigenetics for a while now; it could be the answer to psychosis,schizophrenia, bipolar and alzheimers. When I read about it, my first thought was someone had to take a look at a brain, as they did here for further investigation and research.

It's one of the top searches on my blog, and significant, at least for now anyway.

From the studies linked in my post:

"Epigenetic misregulation is consistent with various non-Mendelian features of schizophrenia and bipolar disorder."

"Methylome network analysis uncovered decreased epigenetic modularity in both the brain and the germline of affected individuals, suggesting that systemic epigenetic dysfunction may be associated with major psychosis. We also report evidence for a strong correlation between DNA methylation in the MEK1 gene promoter region and lifetime antipsychotic use in schizophrenia patients."

"Our data are consistent with the epigenetic theory of major psychosis and suggest that DNA-methylation changes are important to the etiology of schizophrenia and bipolar disorder."

I really need to start investing in some medical textbooks because reading abstracts and trying to tie all those little bits of info together by doing wiki searches and using medical dictionaries to decipher exactly what they are talking about in these studies... it's tedious and obviously isn't helping me really understand these things the way I wish I did.

Could you immagine it? Someone who's hobby is educating themselves about biopsychiatry, neurology, psychopharmacology??? (is it pathetic or am I just overly obsessive about my condition like the doctors tell me?)
Maybe I wouldn't feel the need to take these things on as "hobbies" if I could actually find a damn doctor who remembered thier education enough to share certain info with me that I am interested in learning. And if they all didn't have the attitude problem of seemingly not wanting to educate thier patients... "just shut up and take/do what I tell you, I shouldn't have to explain why".

Oh well, at least I find it interesting. Still it woud be much easier to have a smart doctor who didn't mind being an educator and not just some authorative figure who's (delusionaly thinking they are) in control of my life.

I agree with JC. I wish science researches would stop masturbating on my dime.

All human behavior is caused by a combination of genetic and environmental factors from birth to death. As for this study, hmmmm, like with all such studies, we'd need to know if suffering emotional distress and/or physical pain might cause methylation. Looks like the study determined that at the very least, environment plays a crucial role in suicide and genetics a less important role, or else the study wouldn't have downgraded suicide from genetic which the pharma marketing companies, etc. want to epigenetic. If the press comes off this accurately and reports that "genes play less of a factor in suicide than biopsychiatry predicted it would" it will be a good thing but the problem with a dominant, malignant paradigm like biopsych is that it takes all information as proof it is true even when the info directly contradicts it.

Think about it, if children really were bipolar and treatment of children really could prevent adult bipolar, we'd have studies suggesting that bipolar kids don't become bipolar adults, but we have the opposite, which while counter to the biopsy paradigm, is nonsensically held as proof it's correct.

If suicide were truly all rooted in biology, then there would be no difference the rates of suicide between folks who committed suicide following a trauma of some sort and folks who didn't but there's a huge difference.

Nonetheless, it's good the tide is turning a bit. I expect the huge world financial crisis will finally drive home the idea that unhappiness and a desire for change outside of oneself is not a biological defect but a sane state.

I want my dimes back too Sophia. There's plenty of legitimate research to be done.

Look, I would just like to say that the term "epigenetic" refers to the effect of one or several genes on one or several other genes, and sometimes to the effects of environments on one or several genes. It is not something new. Its a term that's applied to everything, not just disease or psychiatric disorders.

Experience is biology. There are some single allele disorders like cystic fibrosis, and others, usually very debilitating conditions that have clear pathology. No mental illness is among them.

We must face the fact that there will never be a single gene psychiatric disorder. There was never any reason to believe there would be to begin with. The field of psychiatric genetics lack serious scientists as does the all of psychiatry which comprises a group of physicians trained in, well, psychiatry -- and not basic sciences.

It is completely useless to say that behaviors are a "complex interaction of genes and environment", because we know so very little about the basic science behind these things. It's a tautology -- like saying " a man is a man". So its close to useless.

There is a lot of "gene speak" that people rattle off with out knowing enough about. And it's usually promulgated by the science sections of major newspapers, NYT, comes to mind.

Genetics won't help us make better drugs for what gets called mental illness. And theyre probably not even discrete conditions with similar substrates. Thats a question the field is facing now. You can look at any journal and read about it.

The fact is that since the human genome has been mapped within the last 10 or less years -- the data generated has continually knocked down the idea that genes contribute in any significant way to what gets called mental illness -- the crap in the DSM. There was no rational reason to believe that initially. Many scientists now are working from an aging, reductionistic model of molecular biology. They're just filling their time with useless lines of investigation.

A comet will hit the earth before we are able to discern all the "many" "small" epigenetic effects that to contribute to what was arbitrarily defined as mental illness in the DSM when polyester pants and vulgar color schemes were so in fashion.

In other words, we'd all be served by not accepting, uncritically, science that goes against every thread of common sense we have.

I'm sure if you're visiting or commenting at this site, you realized long ago that psychiatrists have absolutely no clue what they are talking about and their results speak more to that than anything.

peace

A psychotic or depressed mind that leeds to poor, wrong or irrational choices can exist. I have experienced it. To deny either side, the possible brain chemical imbalance (methylation) or the environmental/emotional side is wrong, when science is looking for answers.

I agree JC, that genetics won't help create drug treatments; because I believe that medications cannot treat genetic based syndromes, etc. The topic is an interesting one though, for me at least, to attempt to understand what's happening to the brain itself for certain things like Alzheimers, or for example all of the genetic syndromes they tested my daughter for that presents with psychosis. Anyway, it's interesting to think about; I learned more from the genetics dept re: psychosis than I did in the psych dept, which as you can imagine only looked at the psychosis as a reason to medicate my daughter. The genetics people did not bring up medication.

I hope this made sense, my chiming in here is based on interest of the topic, though I have no answers at all.(and am skeptical of any answers happening in the near-future, esp if it's always based on psych drug testing/and use for answers for treatment.)

JC,

What troubles me about this is the long term goal of folks like Torrey and NAMI, which seems to be a genetic test to determine who gets forcibly medicated regardless of "symptoms" when of course no two psychiatrists agree what schizophrenia or bipolar disorder or depression are and of course this study involved suicide, not folks with psych labels, from what we know currently.

Sally,

Let me assure you, and I am being completely serious about this -- as far as brain science goes, researchers in any field will sooner develop a genetic test to detect your 5th favorite flavor of Baskin Robin's ice cream than they will to detect mental illness in people without overt symptoms. So, rest assured. As far as worrying about that goes -- you have nothing to worry about. But I understand why you would. Torrey is... there are no words.

We actually know very little about mental illness and biology, but of course we hear huge, wild, overstated pronouncements all the time. If you don't have anything to go on, you make wild claims and speculation. Most valid research findings never turn out to be so spectacular as what gets spouted in this field.

There will never be a test like that in 15 of our lifetimes -- well, you get the picture. But most of this penchant for spectacular advances stems from the 90's when we thought we would discover cures to every human condition once the genome was mapped. It did not turn out to be so, and as far as psychiatry goes, well, the "decade of the brain" is roundly over. Thank God.

Take care.

Methylation is linked to "histadelia" a diagnosis in orthomolecular psychiatry. google it!

Sally said: "What troubles me about this is the long term goal of folks like Torrey and NAMI, which seems to be a genetic test to determine who gets forcibly medicated ...."

I'm pretty sure that in Torrey's ideal world, everybody would be forcibly medicated (except for shrinks, of course), just in case. What an asshole.

Since methylation is such a chemically ubiquitous phenomenon, my first reaction was to wonder if the changes noted by the researchers are a potential cause of suicidal ideation, or perhaps a consequence of other factors (e.g., "stress") that in themselves contribute to suicidal tendencies.

The fields of people who own livestock are apt to be much denser in excrement than the properties of urbanites without these animals, but this does not imply that shit causes cows.

I agree with amibibextrous, and Goethe, that the confusion between cause and effect creates a potential for many misleading arguements.

That's a great comment Mark, thank you.