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Dr. Bob is Robert Hsiung, MD,
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Posted by chiron on May 10, 2007, at 23:03:04
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressant » john anderton, posted by Racer on May 10, 2007, at 21:49:02
I have been on antidepressants most of the time for about 20 years. I do feel that they now make me cycle. But all of the mood stabilizers make me worse - some much, much worse. So I am pretty much screwed either way. I am just starting to try doing no meds. I still believe in meds, but for some reason they are making me worse. I don't know what I am going to do. I am not good w/out meds, I am just better than I am with them.
Posted by Johann on May 10, 2007, at 23:44:48
In reply to Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by john anderton on May 10, 2007, at 16:08:07
> 1. How many of you have had success with the use of anti depressants on a long term basis without them pooping out or agitating you to wear you quit the med or switch to a new one?
Not me. After about 30 years I switched to mood stabilizers after realizing I had Bipolar Spectrum Disorder.
> 2. How many of you either with diagnosed bipolar or undiagnosed bp but maybe on the spectrum have had long term success on AD's with a combination of mood stabilizers?
After a cycling response (near suicidal), I stopped with ADs.
> 3. How many of you successfully use just a mood stabilizer or combos of mood stabilizers?Yes to that.
> 4. It appears that the best mood stabilizers are lithium, which helps with classic bipolar 1, depakote which can help with rapid cyling and mixed states, and lamictal, which has some perpensity for bipolar depression in some people but just failed several test for the treatment of acute illness.
I would agree.
> Do you all think that it is reletively safe to use anti depressants so long as a mood stabilizer is aboard?
It's not uncommon.
> This may seem like a bit of a stretch, but I think that recurrent unipolar depression is a form of bipolar disorder...I think it's probably more complex than that.
Johann
Posted by notfred on May 11, 2007, at 1:22:30
In reply to Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by john anderton on May 10, 2007, at 16:08:07
"This may seem like a bit of a stretch, but I think that recurrent unipolar depression is a form of bipolar disorder..."
20+ yrs on AD's for unipolar depression and I have never cycled nor had anything close to hypomania.
Posted by bipolarspectrum on May 11, 2007, at 8:18:20
In reply to Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by john anderton on May 10, 2007, at 16:08:07
Hi,
I was treated by many docs for many years as a unipolar depressive.. tried every unipolar drug... nothing helped...I am now on a combination of divalproex/lithium with exceptional results...
I understand the current approach amongst the mood disorder speciality clinics is to use mood stabilizer(s) unless antidepressants seem absolutely necessary..
bps
Posted by sunnydays on May 11, 2007, at 8:37:37
In reply to Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by john anderton on May 10, 2007, at 16:08:07
From a recent research paper I did at school, there is significant evidence that depression and bipolar have a similar genetic basis, so it's not too farfetched to think that recurrent unipolar depression and bipolar are on the same spectrum - many people doing genetic research now think so. I just started Lamictal in addition to Lexapro about two months ago, because with the Lexapro alone I was having really bad mood swings - I could be happy one minute and suicidal the next. The Lexapro worked well for about a year, but then the mood swings came. But with the Lamictal added I feel normal for the first time in maybe forever. I may be on the bipolar spectrum, although much closer to unipolar depression, because my brother has rapid-cycling bipolar I.
sunnydays
Posted by linkadge on May 11, 2007, at 13:17:40
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!! » john anderton, posted by sunnydays on May 11, 2007, at 8:37:37
>From a recent research paper I did at school, >there is significant evidence that depression >and bipolar have a similar genetic basis,
I don't know how they would come to that conclusion seeing as nobody has descovered a single gene that accounts for all of the current manifestations of depression. Even some of the so called *candidate* genes are only showing up in a small fraction of those diagnosed with depression.
Linkadge
Posted by Squiggles on May 11, 2007, at 14:24:32
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by linkadge on May 11, 2007, at 13:17:40
This gene business is good fodder for
the sceptic. It certainly doesn't *seem*
like mental illness is genetic, and it has
such a multitude of thoughts, reflections,
actions, intentions, ideas, memories, sensations,
perceptions, etc. in consciousness, that it is
hard to believe that *1* solitary gene can
be responsible for mental illness.But, I think that there are two possible fallacies
in this way of thinking: one, that there are other conditions of the body and brain which own their origin to a single gene, and two, we haven't really proven what one gene is capable of in its "mental map" manifestation.In searching on this subject, i found a really neat article here:
"Gene Linkage and Bipolar Disorder/Manic Depression by Debbie Wang.
http://serendip.brynmawr.edu/biology/b103/f01/web2/wang.html
Posted by Klavot on May 11, 2007, at 15:09:09
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressant, posted by Squiggles on May 11, 2007, at 14:24:32
The renowned evolutionary biologist Richard Dawkins points out that the analogy of one's DNA being like a blueprint for your body is a poor analogy. Every part of a blueprint corresponds to a particular component of the building or machine that it represents. He says a better analogy would be that your DNA is a *recipe* for the construction of your body. Individual letters or words in a recipe for a cake do not correspond to particular parts of the cake. Likewise, individual genes in one's DNA do not correspond to particular characteristics in your body. Thus, it is unlikely that there would be such a thing as a "depression" gene or a "bipolar" gene that can be switched on or off. If depression and bipolar disorder do have a genetic basis, such basis would represent as a complex combination of gene variations.
Klavot
Posted by Squiggles on May 11, 2007, at 15:22:05
In reply to Re: genetic basis for mental illness, posted by Klavot on May 11, 2007, at 15:09:09
> The renowned evolutionary biologist Richard Dawkins points out that the analogy of one's DNA being like a blueprint for your body is a poor analogy. Every part of a blueprint corresponds to a particular component of the building or machine that it represents. He says a better analogy would be that your DNA is a *recipe* for the construction of your body. Individual letters or words in a recipe for a cake do not correspond to particular parts of the cake. Likewise, individual genes in one's DNA do not correspond to particular characteristics in your body. Thus, it is unlikely that there would be such a thing as a "depression" gene or a "bipolar" gene that can be switched on or off. If depression and bipolar disorder do have a genetic basis, such basis would represent as a complex combination of gene variations.
>
> KlavotInteresting. I don't know much about biology.
The "recipe" analogy would have to allow for exogenous factors intervening with an initial pristine plan. Interference--chemical or environmental could warp that plan. However, such factors would have to be gross, as for example, in teratogenic forms of a definite species form, like a cat with too many toes, or Down's Syndrome, or bicephalus. Such things are rare.Bipolar and depression may actually be "normal", in the sense that they are analogous to hair colour or eye colour. It is only the social context that make them weird, whereas the teratogenic forms are obviously an interference with the recipe.
In the end, the proof is in the pudding. :-)
Squiggles
Posted by sunnydays on May 11, 2007, at 16:25:05
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by linkadge on May 11, 2007, at 13:17:40
> I don't know how they would come to that conclusion seeing as nobody has descovered a single gene that accounts for all of the current manifestations of depression. Even some of the so called *candidate* genes are only showing up in a small fraction of those diagnosed with depression.
>
> LinkadgeDepression is a complex disorder just like heart disease, as such, no single gene will account for all manifestations - different genes contribute to susceptibility. Complex disorders are also influenced by environmental factors, so many of the genes that influence them have absolutely no effect without specific environmental factors being present.
The locus I was thinking of that has similar effects in depression and bipolar is called 5-HTTPR. The short allele of this gene is correlated with depression if a person experiences significant stress early in life or more recently. It is also associated with taking longer to respond to SSRIs and with poorer response overall to SSRIs. The short allele has also been found to be associated with nonresponse to lithium prophylaxis in those diagnosed with bipolar I. Lithium is thought to affect the serotonergic system, although the exact mechanism is not known, so it seems depression and bipolar can both be treated with drugs that affect the serotonin system and this gene also affects that system and seems to contribute to at least some of the symptoms of those disorders.
Again, it is important to understand that NO single gene will account for all of the cases of ANY disease or disorder at all except for the simply inherited Mendelian disorders. Depression and bipolar are not Mendelian. Looking for a single gene to explain everything is a common misunderstanding of how genetics works in both the popular media and among many individuals.
Hope this explains what I meant when I made that statement.
sunnydays
Posted by Johann on May 11, 2007, at 16:30:01
In reply to Re: genetic basis for mental illness, posted by Klavot on May 11, 2007, at 15:09:09
Well put, or restated, or whatever.
> The renowned evolutionary biologist Richard Dawkins points out that the analogy of one's DNA being like a blueprint for your body is a poor analogy. Every part of a blueprint corresponds to a particular component of the building or machine that it represents. He says a better analogy would be that your DNA is a *recipe* for the construction of your body. Individual letters or words in a recipe for a cake do not correspond to particular parts of the cake. Likewise, individual genes in one's DNA do not correspond to particular characteristics in your body. Thus, it is unlikely that there would be such a thing as a "depression" gene or a "bipolar" gene that can be switched on or off. If depression and bipolar disorder do have a genetic basis, such basis would represent as a complex combination of gene variations.
>
> Klavot
Posted by Squiggles on May 11, 2007, at 16:35:31
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by sunnydays on May 11, 2007, at 16:25:05
May i ask what is Mendelian? All i recall was
something to do with plants by Mendel. And what
is the significance of a Mendelian gene to behavioural abnormalities. Also, would you say
that homosexuality is a more-than-one-single-gene phenomenon, for example?tx
Squiggles
Posted by linkadge on May 11, 2007, at 16:36:44
In reply to Re: genetic basis for mental illness, posted by Klavot on May 11, 2007, at 15:09:09
An interaction of multiple genes and the environemnt?
While depression or bipolar disorder may be mildly heritable, there could be reasons beside genes for that. Poor nutritional status, for instance, can be passed on from mother to child.
Omega-3 deficianct mothers would give birth to omega-3 deficiant children for instance.
Then of course epigenics.
Linkadge
Posted by linkadge on May 11, 2007, at 16:38:50
In reply to Re: genetic basis for mental illness, posted by Squiggles on May 11, 2007, at 15:22:05
Exactly. Bipolar disorder may have been a highly advantagious disposition.
Cyclic levels of energy and motivation may have timed themselves well with cyclic demands for food, transportation, battle performance, who knows.
Linkadge
Posted by Johann on May 11, 2007, at 16:54:09
In reply to Re: genetic basis for mental illness » Squiggles, posted by linkadge on May 11, 2007, at 16:38:50
A cyclicity of mood may have been adaptive evolutionarily, but not BPD, which by defintion impairs effective functioning.
> Exactly. Bipolar disorder may have been a highly advantagious disposition.
>
> Cyclic levels of energy and motivation may have timed themselves well with cyclic demands for food, transportation, battle performance, who knows.
>
> Linkadge
Posted by linkadge on May 11, 2007, at 17:01:25
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by sunnydays on May 11, 2007, at 16:25:05
>Depression is a complex disorder just like heart >disease, as such, no single gene will account >for all manifestations - different genes >contribute to susceptibility. Complex disorders >are also influenced by environmental factors, so >many of the genes that influence them have >absolutely no effect without specific >environmental factors being present.
>The locus I was thinking of that has similar >effects in depression and bipolar is called 5->HTTPR. The short allele of this gene is >correlated with depression if a person >experiences significant stress early in life or >more recently.I have read some of these studies. But really, why do you think they are focusing on the serotonin transporter gene? Simply because this is the target for antidepressants. The effects of antidepressants were discovered by accident. So, its really just reverse logic. Its just like all of the studies designed to find an abnormality in the DAT transporter in ADHD on account of the stimulants affecting DAT. There are hundreds and hundreds of studies. Just as many show no association as do an association.
>It is also associated with taking longer to >respond to SSRIs and with poorer response >overall to SSRIs. The short allele has also been >found to be associated with nonresponse to >lithium prophylaxis in those diagnosed with >bipolar I.Well this would make some sense. If the individual has an overall lower metabolism rate of serotonin, then pushing it lower with SSRI's is probably not going to be terrably theraputic.
>Lithium is thought to affect the serotonergic >system, although the exact mechanism is not >known,A number of studies show that lithium interacts with the presynaptic 5-ht1b autoreceptor. By desensitizing or acting as an antagonist at 5-ht1b autoreceptors, lithium potentiates serotonin release in certain areas of the brain.
>so it seems depression and bipolar can
>both be treated with drugs that affect the >serotonin system and this gene also affects that >system and seems to contribute to at least some >of the symptoms of those disorders.Perhaps. This does not account for the clinical efficacy (or lack therof) of drugs like valproate, carbamazapine or other mood stabilizers. Lithium too, affects a heck of a lot more than just serotonin. GSK-3b, BCL-2, PKC, glutamate, PIP2, Inositol metabolsm, sodium channels, the list goes on.
One needs to ask themselves just how strong the association is between the SS varient of the serotonin transporter and lithium failure, as well as the interaction of other genes. For instance, some studies have shown that certain varients of GSK-3b genes are associated with lithium response.
One needs to also look at how lithium and SSRI's differ. Lithium decreases PKC, wherase antidepressants increas it. Lithium lowers GSK-3b wherase antidepressants increase it. Some even suggest that the effect of SSRI's has nothing to do with serotonin reuptake inhibiton, but infact has to do with modulation of the potent gabaergic nerosteroid allopregnanalone (sp.). Lithium also tends to increase monoamine uptake, (or at least monoamine metabolism). So, in general I wouldn't say that one similarity between a medication makes the disorders alike.
>Depression and bipolar are not Mendelian. >Looking for a single gene to explain everything >is a common misunderstanding of how genetics >works in both the popular media and among many >individuals.What I mean is that I think any link between bipolar and unipolar disorder would be very weak at this point in time.
Linkadge
Posted by Squiggles on May 11, 2007, at 17:03:18
In reply to Re: genetic basis for mental illness, posted by Johann on May 11, 2007, at 16:54:09
I can imagine a cyclicity of mood actually belonging to seasonal changes, and evolving into something else. To say that something has an evolutionary advantage in the Darwinian sense, is sooo hard to prove. I am not sure that everything that changes in an organism over time, does so in an intelligent, adaptive manner-- it may actually be a response to an environmental threat at time X, but not at time P.
But, to look for statistical clusters at Chromosome 11 for BP for example, and compare the Amish populations in Pennsylvania to Java ones, and find a 98% correlation in one versus 10% in another, may provide some certainty regarding the heredity of mental illness.
But how do they look at genes anyway? Sorry, I am out of my depth, and you don't have to reply. I can do my own research i suppose.
S
> A cyclicity of mood may have been adaptive evolutionarily, but not BPD, which by defintion impairs effective functioning.
>
>
> > Exactly. Bipolar disorder may have been a highly advantagious disposition.
> >
> > Cyclic levels of energy and motivation may have timed themselves well with cyclic demands for food, transportation, battle performance, who knows.
> >
> > Linkadge
>
>
Posted by sunnydays on May 11, 2007, at 17:12:29
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressant, posted by Squiggles on May 11, 2007, at 16:35:31
> May i ask what is Mendelian?
*** It means one gene is responsible for the disorder. Examples of such disorders are Turner Syndrome, etc. They are inherited in specific patterns and based on whether you have the specific gene or not determines whether or not you have the disorder.
All i recall was
> something to do with plants by Mendel.*** Yes, Mendel studied pea plants. For example, if a pea plant has a form of one gene, the peas will be yellow, but if it has two 'green' copies it will be green. It's a lot easier explained with a picture, unfortunately.
And what
> is the significance of a Mendelian gene to behavioural abnormalities.**** I don't know of any behavioral abnormalities that are simply inherited like Mendelian disorders are.
Also, would you say
> that homosexuality is a more-than-one-single-gene phenomenon, for example?*** One of my classmates did a research project on that, and found that most of the researchers today think that multiple genes contribute to it, as well as environment. It's a complex trait.
sunnydays
Posted by sunnydays on May 11, 2007, at 17:16:51
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by linkadge on May 11, 2007, at 17:01:25
I don't know enough to adequately respond to your post, but I think in general I agree. The drugs all affect many things in the body, because everything in the body is interconnected.
sunnydays
Posted by Squiggles on May 11, 2007, at 17:23:47
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressants!!!, posted by sunnydays on May 11, 2007, at 17:16:51
One thing seems certain-- whether depressions
are genetic or not, they have to be treated without
access to the genetic make-up, unless of course you eradicate certain genetic pools, believed to be carriers. But a lot money is being spent on the research. I don't really see the point, except for scientific curiousity, rather than treatment.Squiggles
Posted by linkadge on May 11, 2007, at 17:44:02
In reply to Re: genetic basis for mental illness, posted by Johann on May 11, 2007, at 16:54:09
>A cyclicity of mood may have been adaptive >evolutionarily, but not BPD, which by defintion >impairs effective functioning.
But assesment of effective functioning is completely relative to the task at hand.
For instance racing mind, excess energy, or self confidence may hinder the proper affixation of postage stamps, but in battle they might save your life!
Linkadge
Posted by Squiggles on May 11, 2007, at 17:47:23
In reply to Re: genetic basis for mental illness » Johann, posted by linkadge on May 11, 2007, at 17:44:02
You could just as well say that about
thyroid disorder-- the cyclicity is not
exactly good timing, at least not as
a remnant of a once advantageous trait.Squiggles
Posted by sunnydays on May 11, 2007, at 19:10:03
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressant, posted by Squiggles on May 11, 2007, at 17:23:47
If you know the genetic basis of a disorder, drugs can theoretically be designed to interact with the proteins those genes code for. Research underpins all biological treatment for any disorder.
sunnydays
Posted by Squiggles on May 11, 2007, at 20:15:49
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressant, posted by sunnydays on May 11, 2007, at 19:10:03
> If you know the genetic basis of a disorder, drugs can theoretically be designed to interact with the proteins those genes code for. Research underpins all biological treatment for any disorder.
>
> sunnydaysThat sounds promising, but the match must be
as difficult to get as the current AD--depression-type.Squiggles
Posted by linkadge on May 12, 2007, at 8:11:25
In reply to Re: Bi Polar/Recurrent Unipolar and Antidepressant, posted by Squiggles on May 11, 2007, at 20:15:49
But we are still just working with varients of drugs that were discovered by accident.
I don't know how much the acitions of these drugs are methodically planned out.
Linkadge
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