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.