Please read this all the way to the end before responding. I am generally pretty good at reading medical journalese, I am a nurse that works in psycho-geriatrics, I read a lot of drug monographs and understand at least the theory behind them. For some reason this sentence is not making sense to me.
(It is from Wikipedia, I will grant that. But I was using it to understand a medical journal article… which I did mainly understand. I understand more or less the serotonin neurotransmitter functions and how reuptake inhibitors allow more serotonin to enter the synapses. What I do not understand is the “repeat length polymorphism in the promotor of this gene” part… . Could that be familial? Genetic?
This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is the target of many antidepressant medications, including those of the SSRI class. It is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in sudden infant death syndrome, aggressive behavior in Alzheimer disease patients, post-traumatic stress disorder and depression-susceptibility in people experiencing emotional trauma.
The bolded part is referring to a change in the DNA (polymorphism) upstream of the gene. It doesn’t affect the protein itself, but how the protein is regulated.
Repeat polymorphism are sequences of DNA that are repeated (eg AATAATAAT) and are prone to transcription error in which the sequence gets duplicated it otherwise enlarged.
Promoter: gene sequences that control expression of the gene itself, not part of the protein coding info.
The details of the neuroscience, I’m not that familiar with, to explain whether the science makes sense.
If you have one polymorphism, then your serotonin uptake works better or worse than if you had a different polymorphism. Regarding depression (and I assume the others are similar), one thing associated with it is too much reuptake. Your nervous system decides that it is done with serotonin and breaks it down (as outlined in the non-bolded part). But it does that prematurely if you have the specific polymorphism. SSRIs inhibit reuptake, thus increasing serotonin in the synapse. That isn’t the only way to do so, but the most common to treat these disorders.
Just one extra, possibly unnecessary bit of clarification: A polymorphism is any part of a gene that is known to take different forms in different people. For example, a single nucleotide polymorphism (SNP) is a specific spot on the gene where some people have one nucleotide (say, adenosine) and other people have a different nucleotide (say, thymine).
Thank you fpolymorpholgythe detgenetic ndunderstandable replies. I really dont understand genetics and DNA level biology enough, I can tell. One question… would these polymorphisms of the serotonin receptors etc be a heritable trait? Would the polymorphisms be changed in some way and be passed down to subsequent generations…or be expressed by depression in some offspring and dementia in others?
The “short” version can be carried by parents with little impact. On average one out of four of their children could get two of those versions. The thinking is that that “homozygous” condition, having two of the “short” versions, puts people at higher risk of adverse responses to stress and predict response to SSRIs. Having two “long” versions or only one “short one” does not. There also seems to be an impact of gender (stronger in males) and whether or not other gene variants are also present.
I have no information about these polymorphisms and dementia but it makes sense that the exact combination of other gene polymorphisms and experience would have divergent impact on what sorts of clinical pictures were seen.