A Suicide Epidemic in Utah, and One Neuroscientist Thinks He Knows Why | Hacker News Reader

A Suicide Epidemic in Utah, and One Neuroscientist Thinks He Knows Why

mic.com

114 pointsjonah55 comments

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.

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.

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

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.

The data seems to point towards a much more likely correlation, rural areas seem to have a higher rate of suicide. How else does Oklahoma and West Virginia get explained? It'd be much better to break the data down by county. Even still, it's all probably just correlation. Another take: http://www.dailyyonder.com/booze-guns-and-rise-rural-suicide...

The article implies that the location is causative, IE that living in mountainous, rural regions causes depressive symptoms. You could also make the argument that people with depressive symptoms might be drawn to mountainous, rural regions.

I don't have any hard evidence or a citation to back this up, but someone once suggested to me that the reason suicide rates are higher in Western, "frontier" states is that people with mood disorders might tend to migrate away from population centers. Population density is highest on the East Coast, decreases through the Midwest, and reaches its nadir in the Rockies. Then it increases again as you reach the West Coast.

I think we could explain their data using that correlation alone. Based on what I'm reading from the article, I'd say my theory is about as strongly supported as theirs based on the available evidence.

I am not certain that population density reaches its nadir in the Rockies. In those states (Utah and Colorado in particular), the population is clustered in towns and cities along the Wasatch and Rocky Mountain ranges. In the midwest there is a more rural distribution.

It would be interesting to look at suicide rates by population density at level lower than state or county.

This could very easily be ruled out by examining whether the people in the sample were raised in those places or moved there as adults.

The majority of Utah residents, like 90%, live in urban and suburban areas. It is not a particularly rural state.

Rural areas tend to have more risk factors -- social isolation; elderly population; poor population; access to means and methods (In England farmers have access to shotguns; vets have access to meds); etc.

Risk of suicide in rural areas tends to be higher even if the total numbers are smaller.

http://www.worldlifeexpectancy.com/california-cause-of-death...

That site has some nice data to noodle around with.

I hope he has better evidence than what is presented in this article - a line chart that should have been a histogram and which muddies the data by inverting the supposed cause and effect; a study that shows a decline in the psychological well being of a group of Marines after a month training at altitude that is blamed (incredibly) on the altitude and not the training; various anecdotes.

I was confused by the chart. Higher suicide rates cause higher altitudes? If the axes were reversed, the interpretation would seem very different (rate shoots up for a small change in altitude, then levels off at higher altitudes). Also the buckets are unequal (but maybe that's what vingtile means. What is a vingtile, anyone?)

I believe a vingtile is like a quartile, except that there are 20 of them instead of 4 (vingt = 20 in French). So I'm guessing each bucket contains an equal number of counties, rather than being an equal size.

I hate teaser headlines like this. How about something straightforward, like "Low-oxygen air messes up serotonin / dopamine levels, can lead to suicide"?

But that's not really a fact, is it? It's a hypothesis from one scientist. There's enough sensationalism in science reporting already. Putting a complex idea into one sentence that is wrong isn't any better than a teaser.

http://xkcd.com/882/

http://www.smbc-comics.com/index.php?db=comics&id=1623

> Low-oxygen air messes up serotonin / dopamine levels

Phrased this way, I'm pretty sure—anecdotally—that at least the converse of that is true, so I would certainly believe a correlation.

I tend to get migraines when in rooms with low-quality/"stuffy" (i.e. low-oxygen, high CO2) air, for example cars with the windows up and vents off. Oddly, deep breathing or purposefully hyperventilating does nothing to alleviate this, so it's probably more a "judgement" by my brain of the air quality than any physiological necessity.

It used to happen only rarely, but when I began taking dopamine agonists, it now happens far more often. It also doesn't seem to happen if I'm dozing off in a room that happens to be stuffy. So, it feels like my brain has a bar for air-quality, below which it will get rather upset at me—and that that bar goes higher the more awake+stimulated it is.

I could believe, if this is a Regular Human Thing, that some bio-feedback mechanism on top of this would then lead people who live in chronically low-air-quality environments to produce fewer of the neurotransmitters that put them in awake+stimulated states, and more of the ones that put them in dreary/dozing/hibernating states.

> When Renshaw peddled his altitude-suicide theory around the mountain states in 2008, he faced prickly reception. Renshaw heard that Utah's governor at the time, Jon Huntsman, was disgusted that the state would fund the anti-Utah research. Huntsman's staff did not respond to a request for comment.

You've got to be kidding me. Whether or not Renshaw's theory pans out, it's "disgusting" to me that a governor would hide research just because it interferes with the economy, rather than considering the well-being of his state's inhabitants.

If I was a politician and there was research indicating something was (or might be) causing medical problems, I would increase funding to figure out what's going on and look for solutions. The laws of physics don't respect political correctness; you can't just shove them under the rug if it hurts your state's tourism.

The NC GOP legislated against recognizing studies on sea level rise. http://www.reuters.com/article/2012/07/03/us-usa-northcaroli...

I'm not sure, but I think it would be more accurate to say they decided not to endorse a government panel's study (perhaps contrary to the default custom).

Which is actually the correct course of action: the government should neither endorse or denounce scientific studies.

Rather, it should be up to real estate investors, insurance companies, homeowners, etc. to decide the level of risk they face from rising water and whether or not they want to take that risk.

And they should not all be required to go by the "official" North Carolina projections. That is just silly. They should be allowed to use their own, independent judgement.

I would rather this scientist travel to all of these high-desert westen counties and live there for a year before making his claims. I've spent a lot of time in many of these areas, and this paper seems tone-deaf to common sense. These are harsh environments that are not hospitable to human habitation. Its not rocket science that these are tough places to live. Altitude is about a 3rd order issue.

http://nepalitimes.com/news.php?id=2905

Its pretty irresponsible to extrapolate that the Nth order element of the environment is the "key issue", however. Thats a vast oversimplification.

On the fip side, saying "people living in harsh environments on the edge of society, and with low pay, have sub-average mortality expectations" has so many caveats and banalities it doesn't make for a good Academic paper.

I can't blame the governor on that one. I'm pretty sure there is an xckd about this topic somewher.

This article was more interesting than I expected. Notably it proposes a mechanism that I hadn't heard suggested before:

> Renshaw believes that altitude has an impact on our brain chemistry, specifically that it changes the levels of serotonin and dopamine, two key chemicals in the brain that help regulate our feelings of happiness.

It would have been interesting to see that heat map extend into Canada to see if the trend along the Rockies continued as expected. I found the following paper that at least anecdotally fits this theory:

http://www.pembina.org/reports/10_suicide.pdf

Apparently Calgary is going through a suicide epidemic:

"suicides are the leading cause of death for boys and men 10 to 49 years of age, ahead of murder, traffic accidents, and all other causes of death in this age group"

Note that Calgary is at high altitude as well, roughly 3500 ft.

When you restrict to men between 21 and 65 you find suicide is one of the leading three causes of death, and often the leading cause of death, in many places.

California has better than US average rates for death by suicide, but that is because the death rate in older people is unusually low. When you look at rates for younger people you find california does slightly worse than the US average.

Suicide is, sadly, very common.

Calgary has also horribly cold winters which forces a lot of people to stay inside most of the winter. Maybe someone should do a correlation study with days/year where temperature doesn't exceed 20F (I know correlation != causation but at least it's one more hypothesis) . I personally feel depressed on days where I have to stay inside all day, and just taking a walk outside for half a hour uplifts my mood quite a bit.

1. "Before training, the Marines reported more balanced mood levels than average college-aged men. By the time they finished, they described mood symptoms comparable to those of psychiatric patients. Ninety days later, they were just as sad and agitated."

Maybe the physical and phychlogical beat down has something to do with mood? Plus--the realization that the military is not quite what it promised?

2. "Serotonin, an inhibitory neurotransmitter, helps stabilize emotions." I guess that's fact these days? Maybe you should include all the studies, along with the metadata, and make these magical claims?

3."By Renshaw's estimates, the brain makes about 20% more dopamine in the mountains." That's quite an estimation on a neurotransmitter that we can't even test for.

4. "SSRIs are probably no more effective than prescription-plan tic tacs." Maybe that should be the title of the article, and redact every other sentence?

5. "You tell me how Salt Lake City and Las Vegas have the same culture." You can't use Nevada(maybe the most depressed state in the nation) as a control. What happens in Vegas stays in Vegas--your liver, you savings, your dignity.

6. "But 30 years after seasonal affective disorder got its name, SAD sufferers plant themselves in front of light boxes to combat the winter doldrums without anyone raising any eyebrows." Again, it's still just a theory. I've never seen a Psychiatrist pull a light box out of his locked box of sample medications.

7. "When it comes to subjects as biologically and environmentally thorny as mental health and suicide, Renshaw said, the answer is always more research." Fine--apply for a grant and investigate the suicide rate among the Sherapas.

8. I'm all for research, but keep it tight. Your audience is not as nieve as we were in the 90's.

9. Personally, I found the disparity of income in the mountians of Utah very depressing. The wealthy moved in and prices from lift tickets, rent, eating out all went up. Plus, it went from a rural, mainly blue collar community to more of a buttoned down place where the people talked about investments/money over the more important things in life.

> 9. I found the disparity of income in the mountians of Utah very depressing.

Ironic comment from "marincounty". In my experience growing up in Utah, it seemed the wealthy people moving in all came from California.

The paper:

http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.20...

"Altitude, Gun Ownership, Rural Areas, and Suicide

Namkug Kim, Ph.D.; Jennie B. Mickelson, B.S.; Barry E. Brenner, M.D., Ph.D.; Charlotte A. Haws, B.S.; Deborah A. Yurgelun-Todd, Ph.D.; Perry F. Renshaw, M.D., Ph.D.

Am J Psychiatry. 2011 Jan;168(1):49-54. doi: 10.1176/appi.ajp.2010.10020289. Epub 2010 Sep 15."

This would seem to be one of the most easily controlled studies possible. Some observations of various individuals at various levels of oxygen in hypobaric chambers (some of them come equipped for extended living) would provide solid evidence one way or another for this hypothesis.

Particularly in a controlled environment, assessing the individual's mental health should be straightforward.

And I have to believe that GE likely even has a branch that manufactures hypobaric chambers...

How do you control for the depressive effect of living for extended periods in a hypobaric chamber? Seems like studying people living at different altitudes would be easier, cheaper and less tainted by experimental environment factors.

"How do you control for the depressive effect of living for extended periods in a hypobaric chamber?"

That's precisely what control groups are for. The idea behind using a hypobaric chamber is that you control for 100% of everything, and only vary the oxygen levels - you could trivially simulate 2500 feet, 5000 feet, 7500 feet and 10,000 feet for a test group, while keeping the control groups at sea level - and observe the differences.

The problem with testing people at "different altitudes" - is there are so many other events that could be contributing (sunlight, exercise, diet, etc...) - hard to eliminate confounding factors.

SSRI take 2~3 week to take effect, for some (AFAIK unknown) reason, a few hours in a hypobaric chamber would not be conclusive.

I'm thinking an extended living Hypobaric chamber - have people stay there for a month.

La Paz, capital of Bolivia, sitting at 12000ft, suicide rate: less that 2%. Quito, capital of Ecuador, sitting at 9000ft, suicide rate: around 6%. I think this article wants to start a new 'epidemic' for which 'expensive drugs' must be taken.

I was skeptical when I heard this, as I've grown up in high altitudes. So I tried to do a check on a few other high altitude cities, and the results are somewhat consistent.

Other cities which are high altitude with very high suicide rates include:

Denver, Colorado Springs, Albuquerque, Reno.

I'd be interested if this were also the case in other countries with high plains populations like Tibet, Nepal, Bolivia, Switzerland, etc. Some places have had stable populations for a long period of time, other populations (and individuals) may be newer, relatively speaking --that might be something to investigate as well, if it hasn't.

The article is paid marketing content from GE. Just saying.

Exactly.

So yeah, okay, then Tibetan Monks and people living there should be very unhappy. All the positive comments about ADD and ADHD medications in the article, and the fact this is sponsored by GE makes me feel this is a paid article made to promote more medication and move people away from the real cause that is causing more and more suicides all the time, and that is, mood-affecting medication. Do your own thinking.

Direct quote from the article: "There is such thing as too much fresh air" :D

Sherpas and Tibetans have thousands of years of natural selection to develop increased survival ability at altitude. Non-native residents of the mountain west states have only been there for no more than 167 years, having mostly immigrated from lower altitude regions.

Right, and some of the genetic variants have even been nailed. Since we can't randomize people to move to Utah (well, the Mormons and Air Force clearly could by randomizing part of their admissions, but it's unlikely they'd cooperate) and since the hyperbaric chambers offer confounds of their own (either people aren't in there long enough to matter or any resulting depression may be due to confinement), the genetics angle seems like the best way forward: collect genomes along with psychiatric status and altitude, and using GCTA, I think, look for an interaction between altitude & depression; if you can establish a genetic contribution to high-altitude but not low-altitude depression, that strongly supports the claim that altitude can cause depression.

The next area to look, then, would be the native peoples of the Andes. They have a different set of high-altitude adaptations, which aren't as good as the Himalayan ones.

As one who has lived at 5500ft elevation or higher for all but of few of my 40+ years, this is pretty interesting...

I still wouldn't trade the Rockies for anything.

Couple of warning signs: (1) Article is actually a paid advertisement, and doesn't pretend to anything like peer review. (2) "In addition to the statistical evidence, Renshaw collected anecdotes that supported his developing theory." Seriously?

As we don't have anything like a useful theory of what depression is and the details of how neurotransmitter levels are connected to mood, especially over the long term, he's really jumping to conclusions. His statistical correlation is weak, and correlates to a lot of other things (maybe Republicans cause suicide, or proximity to harbors protects you from suicide). He needs a causal mechanism and a LOT better data before this is anything like a useful hypothesis. By the way - lets note that Switzerland's suicide rate is considerably lower that France, and half that of Japan (most of whose population centers are near sea level).

Addendum: I also note that Pakistan, Peru and Nepal report very low suicide rates versus world averages. Usual questions about what "report" means, but one would probably think they would discuss this apparent problem with their theory.

I just wish more than One neuroscientist knew. I've seen such headlines a lot about science, they are sensationalistic but how often does this "one scientist" get the establishment to accept their work through the regular channels - peer reviewed journals - and how long dods it take?

This is a case of SA;DR. Sponsored article, didn't read.

I wanted to read the article, honest I did. But as soon as I saw the General Electric (GE) logo smack-dab in the middle of "Brain.Mic"'s own logo (who the f%^$ does that!?, what self-respecting company, particularly a journalism publisher, DOES that!?), I tuned out. I won't trust a publication that sells itself out that way, and consider the content of the article suspect. Sorry, but that's how I roll.

Read the article, thought Eureka. I moved to SLC to train as an adaptive ski instructor and immediately had those altitude affects, loss of appetite and sleep, irritability etc, that were familiar from lots of time spent sleeping at mountain altitudes (7-8k feet above sea level, generally). Being at about 4300 feet above sea level or so on the east side affected me heavily, tho i figured the native population just got used to it.

(Aside from that, I love Utah

One wonders how this particular correlation rates in comparison with other better-known correlations: youth, maleness, poverty, stress, solitude, access to firearms. I suspect that it would kind of disappear into the noise. I wonder if investigating the effect of poverty (Utah is 40th in per-capita GDP by state, and has the 4th highest unemployment rate) and access to firearms in this particular case might be a bit more diagnostic.

The article seems to be in favor of SSRIs (e.g. Prozac). However, SSRIs have also been linked to suicidal & violent behavior.

http://www.drugwatch.com/ssri/suicide/ http://www.theguardian.com/science/2000/may/22/drugs.uknews

Sorry, I'm not reading a webpage with a busted layout like this: http://imgur.com/TsN7sUg

The top non-scrolling region is quite large, and then they add on a facebook and twitter curved thing as well? Infuriating! Am I the only one seeing this?

It's because the higher you live, the greater you will see the beauty of the world and so, the less you are already self realized, the more you will feel a bigger discrepancy with it. And it can hurt.

I live in a ski town, this might explain why my family tends to sleep so much. I try for 10+ hours per night, which would make sense if I need extra time to replenish seratonin.

Interesting theory, but one which my guess is unlikely to hold up if the study is carried out it in really mountainous, high altitude areas.

A very interesting article. For me two key statements come toward the end.

"Did you know that at high altitude, the brain goes through metabolic changes, and some people can adapt while others can't, based on their DNA?"[Renshaw]

"Renshaw, too, is confident his findings are beyond the realm of a fluke, but he isn't willing to dismiss other explanations for the suicide-altitude connection, including studies on gun access. Multiple overlapping factors, he says, are likely in play."

Did they check the lithium levels in those places?

http://www.nytimes.com/2014/09/14/opinion/sunday/should-we-a...

See http://www.ncbi.nlm.nih.gov/pubmed/23733285 :

"The correlation results showed a negative association between lithium levels and altitude. The regression confirmed a negative association of lithium levels and suicide mortality. Altitude was found to be positively associated with suicide mortality. On the other hand, lithium effects on suicide mortality were found to be moderated by altitude. In lower altitude regions the effect turned out to be negatively related to suicide mortality, while lithium had a positive association in high-altitude regions. These results provide evidence for the fact that the relationship between lithium, altitude and suicide rates is more complex than hitherto assumed."

Reply on news.ycombinator.com