3 ms·

Quite late here, and I wish I had more time to comment. I guess the main point to make is the assertions about effects on serotonin/dopamine systems of higher

by jrapdx3 12y ago

Quite late here, and I wish I had more time to comment. I guess the main point to make is the assertions about effects on serotonin/dopamine systems of higher altitude locations, and effects of these messenger chemicals on mood/cognition are vast oversimplifications of very complex multiple system interactions. To begin with, in important respects characterizing 5HT/DA as "neurotransmitters" is not quite accurate. Certainly 5HT and DA play diverse roles in the brain and elsewhere, but often act as modulators of neuronal firing patterns rather than primary signal transmission itself. Hence not necessarily "excitatory" or "inhibitory" in a direct sense. Something like a gate in an FET modulating current flow between source and drain. We usually think of glutamate as the main excitatory neurotransmitter in the brain, and GABA being inhibitory, but it's not a clean separation, since there can be a range of effects on subsets of receptors. Furthermore, 5HT, DA, and a host of other monamines and peptides have complex interactions to up- or downregulate transmission in neuronal circuits. It may be true that there are correlations among variables of altitude, suicide, or even attentional disorders. However, not only does correlation not imply causality, it's especially ambiguous when there is a potentially unlimited range of contributors, perhaps far too many to factor in to the results. For instance, I live in Oregon where around 90% of the population lives in the Willamette Valley, essentially at sea-level elevation. Yet according to the graphics in the article, Oregon has a high (but not the highest) rate of depression and suicidal behavior, known issues to be sure. We do suffer other conditions like substantially northern latitude, widespread Vitamin D insufficiency, economic stresses, and other factors to take into account. Perhaps the work described in the article could generate some interesting hypotheses, but painting with such a broad brush seems overstating the case and likely to be misleading.

LnxPrgr3 12y ago
This over-simplification has made it hard to find out what my prescriptions might actually be doing for (or maybe to) me. I'm about to say things as a hopefully decently informed patient. Hopefully it'll more useful than "serotonin = happy," but it'll probably contains errors. Corrections and additional information would be greatly appreciated! My GP prescribed two drugs at the same time: citalopram, an SSRI, to treat depression, and hydroxyzine as a sleep aid. I thought that was interesting because hydroxyzine is a 5HT-2a antagonist, which seemed like it'd interfere with the SSRI. It took quite a bit of digging to learn that it probably wouldn't, which still surprises me. My current understanding is SSRIs play a long game—at first, the lower reuptake rate extends serotonin's effect in synapses (but specific subtypes, because boosting the wrong ones makes you puke), but then autoreceptors (feedback mechanism for the transmitting neuron) undo that by causing less serotonin to be transmitted in the first place. But then, eventually they reset, and then the other end of the synapse gets to down-regulate its sensitivity to serotonin, at which point the SSRI's done its actual job. But the reading I did didn't leave me thinking researchers are terribly confident that that's a complete explanation. It would explain the side-effect profile though—especially the absurd increase in anxiety. Treatment is increasing 5HT-2a activity, apparently intentionally, when another drug is a potent anxiolytic blocking 5HT-2a activity. I quit taking the hydroxyzine, but while I was taking it it seemed to be an SSRI side effect off switch. It also made me a zombie the whole next day, which is why I stopped taking it. And of course, the biggest thing I learned: don't let the drugs be alone in their battle against depression. Odds of successful treatment are much better with the combination of drugs and therapy.
- jrapdx3 12y ago
  Medications are tools not answers. All drugs have multiple effects most of which have received little or no study at all. We are not fortune-tellers. It's impossible to predict exactly what effects a drug will have in a given individual. Hydroxyzine is an old drug, with antihistaminic, anticholinergic, and some degree of 5HT2a antagonism. It can have moderate anti-anxiety effect, and may reduce discomfort of opioid withdrawal symptoms. However, some people respond poorly, or even become agitated with use of such agents. While SSRIs block presynaptic 5HT reuptake, this is also known to be a transient effect. Antidepressant action is associated with "downstream" intracellular neuronal changes that are extremely complex and incompletely understood. Specifically, 5HT2a effects are diffuse and connection to particular symptoms tenuous at best. A quick look here should illustrate this point: https://en.wikipedia.org/wiki/5-HT2A_receptor https://en.wikipedia.org/wiki/5-HT2A_receptor Pragmatically, if a medication produces troublesome effects, don't try too hard to "explain" the problem, but definitely don't suffer in silence. Talk it over with the doctor and try other approaches. Psychotherapies can be effective. I agree, it's not an "either-or" situation, rather "all-of-the-above". By all means use the whole range of effective and tolerable tools at your disposal.

by jrapdx3 12y ago

LnxPrgr3 12y ago

This over-simplification has made it hard to find out what my prescriptions might actually be doing for (or maybe to) me. I'm about to say things as a hopefully decently informed patient. Hopefully it'll more useful than "serotonin = happy," but it'll probably contains errors. Corrections and additional information would be greatly appreciated! My GP prescribed two drugs at the same time: citalopram, an SSRI, to treat depression, and hydroxyzine as a sleep aid. I thought that was interesting because hydroxyzine is a 5HT-2a antagonist, which seemed like it'd interfere with the SSRI. It took quite a bit of digging to learn that it probably wouldn't, which still surprises me. My current understanding is SSRIs play a long game—at first, the lower reuptake rate extends serotonin's effect in synapses (but specific subtypes, because boosting the wrong ones makes you puke), but then autoreceptors (feedback mechanism for the transmitting neuron) undo that by causing less serotonin to be transmitted in the first place. But then, eventually they reset, and then the other end of the synapse gets to down-regulate its sensitivity to serotonin, at which point the SSRI's done its actual job. But the reading I did didn't leave me thinking researchers are terribly confident that that's a complete explanation. It would explain the side-effect profile though—especially the absurd increase in anxiety. Treatment is increasing 5HT-2a activity, apparently intentionally, when another drug is a potent anxiolytic blocking 5HT-2a activity. I quit taking the hydroxyzine, but while I was taking it it seemed to be an SSRI side effect off switch. It also made me a zombie the whole next day, which is why I stopped taking it. And of course, the biggest thing I learned: don't let the drugs be alone in their battle against depression. Odds of successful treatment are much better with the combination of drugs and therapy.

jrapdx3 12y ago
Medications are tools not answers. All drugs have multiple effects most of which have received little or no study at all. We are not fortune-tellers. It's impossible to predict exactly what effects a drug will have in a given individual. Hydroxyzine is an old drug, with antihistaminic, anticholinergic, and some degree of 5HT2a antagonism. It can have moderate anti-anxiety effect, and may reduce discomfort of opioid withdrawal symptoms. However, some people respond poorly, or even become agitated with use of such agents. While SSRIs block presynaptic 5HT reuptake, this is also known to be a transient effect. Antidepressant action is associated with "downstream" intracellular neuronal changes that are extremely complex and incompletely understood. Specifically, 5HT2a effects are diffuse and connection to particular symptoms tenuous at best. A quick look here should illustrate this point: https://en.wikipedia.org/wiki/5-HT2A_receptor https://en.wikipedia.org/wiki/5-HT2A_receptor Pragmatically, if a medication produces troublesome effects, don't try too hard to "explain" the problem, but definitely don't suffer in silence. Talk it over with the doctor and try other approaches. Psychotherapies can be effective. I agree, it's not an "either-or" situation, rather "all-of-the-above". By all means use the whole range of effective and tolerable tools at your disposal.