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A brain surgeon begins an anterior cingulotomy by drilling a small hole into a patient's skull. The surgeon then inserts a tiny blade, cutting a path through brain tissue, then inserts a probe past sensitive nerves and bundles of blood vessels until it reaches a specific cluster of neural connections, a kind of switchboard linking emotional triggers to cognitive tasks. With the probe in place, the surgeon fires up a laser, burning away tissue until the beam has hollowed out about half a teaspoon of grey matter.
This is the shape of modern psychosurgery: Ablating parts of the brain to treat mental illnesses. Which might remind you of that maligned procedure, the lobotomy. But psychosurgeries are different. And not just because the ethics are better today; because the procedures actually work. Removing parts of a person's brain is always a dicey proposition. But for people who are mentally ill, when pills and psychiatry offer no solace, the laser-tipped probe can be a welcome relief.
Original Submission
(Score: 0) by Anonymous Coward on Saturday June 27 2015, @08:38PM
Someone posted a link to a *serum* serotonin test kit. I do not know if serotonin can cross the BBB but that is all the more reason serum serotonin levels will be irrelevant to the putative role it plays in the brain.
What is the data for this? I believe the connection to serotonin here to be wild speculation. They just name something "selective serotonin re-uptake inhibitor", but nothing is really selective. The drugs can be doing alot of things, serotonin may be irrelevant.
(Score: 2) by tathra on Saturday June 27 2015, @09:28PM
i do know if it can cross - it can't. tryptophan, the amino acid precursor to serotonin, can. i don't know much about the serotonin serum level tests but i'm pretty sure that low serum 5HT would also indicate low brain 5HT since tryptophan (its precursor) is going to be roughly evenly distributed between the body and brain, so if there's not enough to produce enough serum 5HT, there wouldn't be enough to produce enough brain 5HT either. low serum 5HT would probably just mean you need a change in diet though.
there are proteins in the brain [wikipedia.org] that take neurotransmitters from the synapses and put them back into vesicles to be used again. "selective serotonin reuptake inhibitor" means it specifically targets serotonin reuptake proteins and blocks them, thus "selective serotinin reuptake inhibitor". you're right that connecting serotonin to depression is wild speculation, but for the wrong reasons. its actually pretty easy these days to find out how drugs work, and how to design drugs to specifically target certain proteins based on design - thats how most drugs are designed these days, by making modifications to molecules with known mechanisms of action. there is often crossover, eg, its still difficult to make a drug that specifically only targets one receptor or receptor subtype (psychedelics, which mimic serotonin, work on many different receptors, beyond just serotonin receptors; opioids, which mimic opioid peptide, work on more receptors than just kappa+mu+delta), but a big reason for this is not just that we don't know the shape of every single receptor and receptor subtype (there's a lot!), but also lots of receptors have similar enough shapes that there will always be some crossover - even dopamine, an endogenous neurotransmitter, can get transported by serotonin reuptake proteins. the better a drug fits into a receptor, the higher its "receptor affinity". typically the stuff with the highest receptor affinities are antagonists (blocking function) or partial agonists (activates or blocks based on dose), but at any rate we still don't know the specific functions of each receptor anyway, so designing a drug to only target one specific receptor subtype can have all kinds of unforseen consequences (although fortunately that helps us find out the function and shape of that specific receptor and if there are even more different receptor subtypes).
remember though, human experimentation is immoral so we can't experiment on humans to find out the receptor shapes, their effects, how they effect the patient's concsciousness, etc. all we can do is work with the knowledge we get and hope for the best, and continue working for there. like i said though, the profit motive is a giant hindrance to this and is the source of too many of the problems. the prevalence of "antidepressants" and the classification of everything as a "disease" that needs to be cured with pills is due to the never-ending quest for profit.
(Score: 0) by Anonymous Coward on Sunday June 28 2015, @12:13AM
I've learned you have to be careful with what these biologists/medical researchers claim. Often the evidence can be interpreted differently but they do not investigate these alternatives. It is also common for there to be blatant conflicting aspects of the data that go ignored or get hidden by averaging. So I tried to find the earliest paper identifying a serotonin transporter which I believe is ref 1.
I'm not sure if you have access but check out the dose-response curves of various SSRIs in figure 2b of ref [1]. Those are all quite steep, what are the hill coefficients? The authors do not appear interested in this inconvenient aspect of the data. Also the Km for serotonin was only 320 nM, which is quite low affinity. What is the extracellular concentration of serotonin in the brain (quickly checking a few papers it looks like that is 1-20 nM)[2][3]? Back to ref [1], there are other issues. They do not tell us whether the treatments had any effect on cell growth or survival. The more cells and larger cells, the larger the intracellular volume exists to hold the serotonin.
I have no idea if these issues have been resolved in later work, but I would warn you against assuming that the textbook is anywhere near correct. It is unfortunate, but you simply need to go check the actual evidence available for each claim that is made and decide for yourself whether it is reliable. This wastes tons of time, but there is no alternative. Peer review has not been functioning for many years when it comes to medical research.
[1] http://www.ncbi.nlm.nih.gov/pubmed/1944572?dopt=Abstract [nih.gov]
[2] http://www.ncbi.nlm.nih.gov/pubmed/?term=1895110 [nih.gov]
[3] http://www.ncbi.nlm.nih.gov/pubmed/10063489 [nih.gov]
(Score: 0) by Anonymous Coward on Sunday June 28 2015, @12:19AM
I forgot to mention one other thing. Isn't it odd how the paper identifying a serotonin transporter does not show ligand binding curve of serotonin to the transporter? They clearly did this experiment because they report the Km value. This is primary information you'd expect to find. I bet that curve looked strange too.