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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by linkline on December 31, 2003, at 12:44:37
am looking for a link that i found on this site (psychobabble) awhile ago to a site which sells DNA tests for home use to test for genetic dispoistion to Seratonin issues. I know that is a very layman-type description, but you can get the gist of my search..... Anybody know the site? I went there last week, so I know it exists, and such a test exists, but failed to bookmark it....duh....please, all i need is the site...no advice about seratonin levels or 'cures'. thanks!
Posted by linkadge on December 31, 2003, at 14:42:45
In reply to DNA TESTING FOR SERATONIN PROBLEMS, posted by linkline on December 31, 2003, at 12:44:37
I don't know, I think something like that wouldn't be terribly accurate.
Linkadge
Posted by linkline on December 31, 2003, at 14:52:56
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by linkadge on December 31, 2003, at 14:42:45
I found the site, and it is a test for Pharmacological reactions to a myriad of drugs, including all SSRI's. In other words, whether you will be affected at all, or adversely thru treatment using these type drugs. And it is incredibly accurate. It is DNA testing, involving genetic precursors and it SHOULD be required before any doctor prescribes anything...which ofcourse they do not. Heck, very few of them even do blood tests or even take your blood pressure!!! But here is the site for anyone interested, http://www.healthanddna.com/orderform.html. It is the DRUG REACTION panel that applies to this situation.
Posted by linkadge on December 31, 2003, at 16:43:44
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by linkline on December 31, 2003, at 14:52:56
Something tells me it is not as clear cut as this. Seeing as no definitive depression genes have yet been identified, I highly doubt that this could predict a responce %100. And what about potential bipolar individuals. Does it have factors to take into acount the possibility of antidepressant induced mania?
Linkadge
Posted by linkline on December 31, 2003, at 16:53:48
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by linkadge on December 31, 2003, at 16:43:44
ok...you are not paying attention to what i am saying. I reported that this site does testing for the effects of SSRI's ( inluding, but not limited to Effexor, Wellbutrin, Valium, Zoloft, Celexa,and many many more drugs, not all of which are even used in psychiatry) on SPECIFIC patients, rather than just guessing as to whether something will help...or even hurt before taking it. . Please go to the site and study it....this is why I asked not to be contacted with anything other than site information....PLEASE go and read the information at the site before discussing it with me. AFTER you read it, then I will be happy to discuss the findings. Other than that, I feel like I am talking to the wall. No offense, but how can we have a discussion that is only one sided???? Read and I will be happy to hear what you have to say. Thanks, and please, I hope you understand...I do not mean to be rude.....I just have a hard time time suffering fools wisely.
Posted by zeugma on December 31, 2003, at 18:21:47
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by linkline on December 31, 2003, at 16:53:48
The drug testing they do here is not testing for serotonin problems. It is testing to see how well you can metabolize certain drugs, including AD's. This is mostly an issue when it comes to drugs such as TCA's which are dependent upon reaching a certain plasma level.
I think there are certain genetic variation involving the 5-HT transporter that have been tentatively linked to response to certain AD's, but it does not appear that this site can screen for that.
1: Mol Psychiatry. 1996 Dec;1(6):453-60. Related Articles, Links
Comment in:
Mol Psychiatry. 1996 Dec;1(6):434-6.A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders.
Collier DA, Stober G, Li T, Heils A, Catalano M, Di Bella D, Arranz MJ, Murray RM, Vallada HP, Bengel D, Muller CR, Roberts GW, Smeraldi E, Kirov G, Sham P, Lesch KP.
Department of Psychological Medicine, Institute of Psychiatry, London, UK.
The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Wurzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Wurzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
PMID: 9154246 [PubMed - indexed for MEDLINE]
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Posted by linkline on December 31, 2003, at 18:39:03
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by zeugma on December 31, 2003, at 18:21:47
AAAARRRRGGGGGHHH!!! i already corrected myself and said that!!!! i understand what the site is, what the testing is, and how the testing can help with understanding one's tolerance to certain AD's!!! --and that the site is NOT about seratonin screening of any type, as I had vaguely thought in my first post--which I mentioned-- I appreciate the note.....but this is becoming redundant.....enjoy the evening, and i Do thank you for the comment...but......
Posted by Larry Hoover on December 31, 2003, at 19:09:02
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by linkline on December 31, 2003, at 14:52:56
> I found the site, and it is a test for Pharmacological reactions to a myriad of drugs, including all SSRI's. In other words, whether you will be affected at all, or adversely thru treatment using these type drugs. And it is incredibly accurate.
It is not accurate, it is specific. Those are not synonymous. Testing for the specific genotype of three cytochrome enzymes will not determine drug response, but only the predicted rate of metabolic transformation of the drug, and only if it is a substrate for that enzyme. If it is, the drug will be converted to metabolites, which must themselves then interact with other genetic elements to determine response. As the latter genetic elements, e.g. transporter subtypes or receptor subtypes, are not being tested here, you know very little more than you started with, and your wallet is somewhat emptier.
> It is DNA testing, involving genetic precursors
Either you don't understand the language, or you don't understand the language. There is no such concept as a genetic precursor to consider.
> and it SHOULD be required before any doctor prescribes anything...which ofcourse they do not.
It would more often predict side effects and drug interactions than pharmacological response. Only in the case where an active metabolite is responsible for the predominant pharmacological effect would cytochrome enzyme activity become a response-related variable, and once again, only if one of those three cytochrome isozymes was involved. There are many dozens of cytochrome isozymes to consider. Dose is the other variable that interacts with cytochrome enzyme activity to determine individual pharmacokinetics.
> Heck, very few of them even do blood tests or even take your blood pressure!!!
Then find a new doctor, would be my advice.
> But here is the site for anyone interested, http://www.healthanddna.com/orderform.html. It is the DRUG REACTION panel that applies to this situation.
It's a start (towards tailoring the drug to the patient), but it is far too limited in scope and applicability to support a $500 fee, IMHO. Please report back to us on the outcome of your personal research.
Lar
Posted by linkadge on December 31, 2003, at 20:38:13
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS » linkline, posted by Larry Hoover on December 31, 2003, at 19:09:02
Posted by BobS. on January 1, 2004, at 19:36:26
In reply to Lar's pretty much summed it up (nm), posted by linkadge on December 31, 2003, at 20:38:13
Stanford Research Finds Gene Variations That Alter Antidepressant Side Effects
STANFORD, Calif. - Researchers at Stanford University Medical Center have identified a genetic marker that can explain why some people experience side effects to common antidepressants while others do not. They also found that a key liver enzyme involved in breaking down these antidepressants surprisingly played no role in the development of side effects nor in how well the drugs worked. The findings may lead to fewer side effects for patients undergoing antidepressant drug therapy."Antidepressants are among the most widely prescribed medications in the world," said lead author Greer Murphy Jr., MD, PhD, associate professor of psychiatry and behavioral sciences. "One of the mysteries at this point is why some people get debilitating side effects and others don't."
To start solving the mystery, Murphy and Alan Schatzberg, MD, the Kenneth T. Norris Jr. Professor of Psychiatry and Behavioral Sciences, wanted to find differences among patients in the function of proteins - and the genes that encode those proteins - that could account for the varied response to drug treatment. Their findings appear in the October issue of the American Journal of Psychiatry.
Good candidate proteins for studying an antidepressant response include the receptors that the drug interacts with in the brain and the enzymes in the liver that metabolize the drugs. Murphy and Schatzberg chose one of each for their research. In what Murphy said is the only double-blind randomized prospective psychiatric genetic study of its kind, the researchers analyzed DNA samples from 246 depressed patients who were randomly assigned either paroxetine (marketed as Paxil) or mirtazapine (marketed as Remeron) for eight weeks.
All of the patients studied in 18 U.S. outpatient clinics were 65 years of age or older. Side effects are particularly relevant in this age group, Murphy said. Older people, for example, are more susceptible to injury from a fall caused by dizziness, which can be a side effect of some antidepressant drugs. "Being able to pick the best drug would be a huge advantage when you are dealing with older people," he said.
The two antidepressants work in completely different ways, though both affect serotonin, a neurotransmitter that binds to specific receptors found abundantly in the brain and peripheral nervous system. Serotonin has many effects, including mood control, but it also affects the gastrointestinal tract, the sleep-wake cycle and levels of alertness.
The researchers looked at one type of serotonin receptor called 5HT2a, thought to be involved in causing antidepressant side effects. Mirtazapine completely blocks this receptor, so the researchers predicted that variation in the 5HT2a gene would not influence mirtazapine side effects. Paroxetine, on the other hand, is a selective serotonin re-uptake inhibitor, or SSRI, which works by allowing more serotonin to remain in the brain. Paroxetine does not directly interact with serotonin receptors, so they remain functional, which can lead to unwanted side effects such as stomach upset, dizziness, insomnia, agitation and sexual dysfunction.
One variation of the 5HT2a gene, based on a single nucleotide change in the DNA sequence, is thought to affect the amount of the receptor on nerve cells. When the researchers compared the version of this gene that a patient had to his or her experience taking the drug, the differences due to gene variation were striking. People with the one version of the gene were much more likely to discontinue therapy due to intolerable side effects when compared to the two other versions (46 percent vs. 16 percent).
In the mirtazapine patients, there was no effect due to the serotonin receptor gene variation, as predicted. The ability of both drugs to work as an antidepressant was unrelated to what version of this gene a patient had.
To explore a different hypothesis - that drug response is directly affected by how efficiently the liver metabolizes the drug - they chose a particular liver enzyme called CYP2D6, a key player in the metabolism of many medications, including paroxetine and mirtazapine. Most people have a normal level of this enzyme, but 7 to 10 percent have a variation in the gene for the enzyme that makes it work very slowly, causing the drug to build up in the blood, potentially leading to significant side effects. Another 3 to 4 percent have genetic changes that cause excessive enzyme activity, resulting in the drug breaking down rapidly, perhaps before it has had a chance to work.
Many in the medical field have assumed that genetic variation in this enzyme is responsible for the side effects a patient experiences. "I can't tell you how often this hypothesis is stated," said Murphy. "Whole marketing campaigns have been built on whether or not a drug interacted with this enzyme."
The enzyme has at least 40 genetic variations, but to their surprise, the researchers found that the variation did not alter treatment outcome or side effects. Murphy emphasized that this study, like all genetic association studies, will need to be replicated, and the results may not apply to other antidepressants. The researchers will further analyze the data they have from this study, looking at more genes to see how they relate to antidepressant efficacy and side effect frequency. "We have many other markers in the pipeline in other candidate genes that we are exploring and so we feel like this is just sort of the first stab," said Murphy.
### Funding for this study was provided by Organon Pharmaceuticals, Inc., the manufacturer of Remeron; the National Association for Research on Schizophrenia and Depression; The Nancy Pritzker Network and the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
Posted by Dr. Bob on January 2, 2004, at 0:53:38
In reply to Re: DNA TESTING FOR SERATONIN PROBLEMS, posted by linkline on December 31, 2003, at 16:53:48
> you are not paying attention to what i am saying... I feel like I am talking to the wall... I just have a hard time time suffering fools wisely.
Please don't post anything that could lead others to feel accused or put down:
http://www.dr-bob.org/babble/faq.html#civil
Thanks,
Bob
Posted by Larry Hoover on January 3, 2004, at 11:49:01
In reply to Linkage and Lar - Any thoughts on this article, posted by BobS. on January 1, 2004, at 19:36:26
Hey, Bob. I hope you don't mind the delay. I wanted to wait a while, and read it again before I answered.
Overall, this was a very balanced summary of what the study showed, and what it didn't. However, it does raise some ideas I'd like to discuss more fully.
> The enzyme has at least 40 genetic variations, but to their surprise, the researchers found that the variation did not alter treatment outcome or side effects. Murphy emphasized that this study, like all genetic association studies, will need to be replicated, and the results may not apply to other antidepressants. The researchers will further analyze the data they have from this study, looking at more genes to see how they relate to antidepressant efficacy and side effect frequency. "We have many other markers in the pipeline in other candidate genes that we are exploring and so we feel like this is just sort of the first stab," said Murphy.
As a first stab, I wonder if people realize just how trivial this information is, in the greater scheme of comprehending how the body works. They looked at two genes, and found an experiential correlation in one of two genes, but that effect was a difference between 16% and 46% of subjects discontinuing due to intolerable side effects. People want to think that genes are 100% or 0% of an effect, not wishy-washy middle of the road numbers like 16% or 46%. Moreover, we aren't told if the discontinuers discontinued for the same reason, or numerous different ones.
There's been a lot of hype about the Human Genome Project (HGP). About how we'll soon understand everything about people, how miraculous treatments are at hand.....Not!
We're mapping the DNA of *one* person. The excerpt I've retained above describes 40 (known) variants of but one gene. Mapping one individual isn't going to tell us a friggin thing about gene variants. We don't even have an idea how genes vary among races. Up until now, most genes are sequenced in white people, and Japanese. There are lots of other people out there. We won't know we've got every gene variant until we sequence every person, not just one white guy.
One outcome of the HGP is the novel idea that there may only be about 30,000 genes in all our DNA (I think there are more, but there certainly can't be less). And I know there are many genes with huge numbers of variants (40 known versions of the CYP2D6 enzyme, for example), but let's settle on an average of six for each gene.
Okay, so how many different people can you construct, if there was a unique individual with every possible combination of those genes? That would 30,000 to the sixth power, or 24,300,000,000,000,000,000,000 individuals. Now, few diseases arise from problems in single genes (diseases like Tay-Sachs and Huntingdon's were identified simply because they involve one gene variant.....those are easy). What about diseases that arise from the interaction of two genes? To consider the possible ways that each of two genes might interact, in all those people, would require consideration of more interactions than there are grains of sand on Earth. If you consider three-gene and four-gene interactions, you're probably dealing with more grains of sand than there are in the Milky Way.
We're also commonly assuming that genes are on or off, or that they're dominant or recessive. Some cases, like eye colour, quite neatly fall into those cute little mental boxes. But that's not the way the vast majority of genes work. They're sort of on, or sort of off. Geneticists call that incomplete penetrance. Factor that into the mathematical possibilities. Just try.
Now factor in disturbances in DNA caused by viruses. And gamma rays from the sun. Environmental effects like exposure to stress, or pathogens, and dietary effects.
My mind boggles. And I hope yours does too.
To back off from what must seem to be a fatalistic viewpoint.....
What we learn changes our ability to guess correctly. A lot of what we "know" is not reproducible in text or mathematical formulae. That's what makes one doctor better than another, methinks. Or one musician. Etc.
I don't know that scientific reductionism is the way to go.....this gene here predicts that effect there 46% of the time.....what do we get from that, really? We already know that certain drugs are safer for geriatric use than others, ya know? Do we need the details?
I don't wanna burst anybody's bubble, but sometimes pin pricks are a part of life too. Like the guy who thought the $500 dollar test was gonna give him insight into what drug to take. Sorry, but, the only thing I can predict from that lab test is that lab will get your $500. Next!
Just my perhaps all too cynical but typically opinionated response.
Lar
Posted by BobS. on January 12, 2004, at 20:25:50
In reply to Re: Linkage and Lar - Any thoughts on this article » BobS., posted by Larry Hoover on January 3, 2004, at 11:49:01
Lar,
Thanks for your opinion. I was on vacation and just got a chance to read it. AD side effects were a particular problem for me. So I found the article interesting, even though it was sponsored by the makers of Remeron. Regardless, after spending years reading on this forum, I believe something impacts a subset of patients using ADs. I guess you think we have a long way to go, before that "something" is found. I was hoping that this might be the beginning of a new dawn, but your analysis indicates otherwise. Let's keep hoping.
Regards,
BobS.
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