Gut feelings

I used to teach a semester-long introduction to neuroscience course.  It was a popular class; let's face it, the human brain and sensory systems are fascinating.  But the problem was, not only is the topic complex, our knowledge of how our minds work is still in its earliest stages.  One of my mentors, Rita Calvo, professor emeritus of human genetics at Cornell University, said to me that if she were a graduate student today trying to figure out what part of biology to study, she'd pick neuroscience in a heartbeat.  "With neuroscience, we're about where we were with genetics a hundred years ago -- we know what structures are involved, we know a little bit about how they work -- but the underlying mechanisms are still largely a mystery."

It's why so often, when a student would ask me a question, my response started out with "Well, it's complicated."  Even simple questions to ask -- for example, "how does our sense of smell work?" -- get into deep water fast.  And in many cases, the answer is simply that we don't have it completely figured out yet.

One realm of neuroscience where this lack of knowledge is particularly troubling is the treating of mental disorders.  The ones I'm most familiar with, because of suffering from them myself -- depression and anxiety -- can be remarkably difficult to treat effectively.  My psychiatric NP, trying to find a medication that would blunt the edge of my depression, said that there's no good way to predict ahead of time which medication will be effective and side-effect-free -- you just have to try them, monitor the situation, mess with the dosage if necessary, and hope for the best.  I had weird side effects from the first three meds I tried -- Celexa killed my sex drive completely; Lamictal gave me the worst acid reflux I've ever experienced; and (worst of all) Zoloft, which is a wonder-drug for some people, made me feel like I was in the middle of a psychological electric storm, with severe agitation, anxiety, sleeplessness, and suicidal ideation.

They got me off Zoloft fast.

We've finally landed on Welbutrin, which is moderately effective -- it evens out the worst days, and doesn't give me any side effects that I've noticed.  So it's better than nothing, but still, far from a miracle cure.

One of the problems with treating depression is that we really don't know what causes it.  It's known to have some tendency to run in families; my mother was chronically depressed, and several other family members have fought varying degrees of mental illness.  This would suggest a genetic component, and that has been supported by research.  Back in 2005, a research review by Douglas Levinson found that there was a small positive correlation between depression and differences in one of the serotonin transporter promoter regions in the DNA, which are involved in the production and transport of one of the most important mood-altering neurotransmitters.  But there are plenty of people in the study who had depressive symptoms and didn't show the gene alteration, and vice versa.

A paper in 2017 by Niamh Mullins and Cathryn Lewis, of Kings College London, was more hopeful; the researchers found several genes that seemed to track fairly well with major depressive disorder within families, but it bears mention that Mullins and Lewis themselves pointed out that genetics can't be the whole picture -- the most recent estimates, from twin studies, are that depression has a heritability of 37%, suggesting that there are multiple genes at work, along with risk factors introduced with what a person went through as a child.

It's complicated.

The latest twist, which was just published last week in Science, is that there may be a contribution to mood disorders from our gut microbiome.  The role of bacteria (beneficial and harmful) in our overall health is often overlooked; but keep in mind that there are more bacterial cells in and on your body than there are human cells, and a great many of them have unknown health effects.  A study in Finland found a significant correlation between development of depression and the presence in the gut of the bacteria Morganella.

Morganella [Image artificially colorized]

Apparently, Morganella is a gram-negative bacterium that has a role in inflammation.  Chronic inflammation has already been implicated in a number of disorders -- not just obvious ones like ulcers and acid reflux, but heart disease, lupus, rheumatoid arthritis, some forms of cancer, and (possibly) Alzheimer's disease.  The inflammation isn't necessarily caused by the same thing in each case, but an increasing body of research suggests that treating the inflammatory response is key to treating the symptoms of some of the most awful diseases humans get.

So, apparently, add depression to the list.  The researchers are up front that this is only a tentative finding; correlation doesn't equal causation, after all.  And even if there was good evidence that Morganella was causing at least some cases of depression, it remains very much to be seen how you'd treat it.  There are (thus far) very few drugs that target only a single pathogen, so the danger is that in trying to eliminate Morganella, you'd simultaneously destroy the healthy part of your gut microbiome -- with highly unpleasant results.

At least this adds another link in the chain.  Diseases as complex as mood disorders are unlikely to succumb to a single treatment strategy.  But as we edge closer to understanding how our own brains work, perhaps we can get a handle on why sometimes they don't -- and perhaps, one day find an approach to treatment that isn't as scattershot and stumble-prone as the one we currently use.

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This week's Skeptophilia book-of-the-week combines cutting-edge astrophysics and cosmology with razor-sharp social commentary, challenging our knowledge of science and the edifice of scientific research itself: Chanda Prescod-Weinsten's The Disordered Cosmos: A Journey into Dark Matter, Spacetime, and Dreams Deferred.

Prescod-Weinsten is a groundbreaker; she's a theoretical cosmologist, and the first Black woman to achieve a tenure-track position in the field (at the University of New Hampshire).  Her book -- indeed, her whole career -- is born from a deep love of the mysteries of the night sky, but along the way she has had to get past roadblocks that were set in front of her based only on her gender and race.  The Disordered Cosmos is both a tribute to the science she loves and a challenge to the establishment to do better -- to face head on the centuries-long horrible waste of talent and energy of anyone not a straight White male.

It's a powerful book, and should be on the to-read list for anyone interested in astronomy or the human side of science, or (hopefully) both.  And watch for Prescod-Weinsten's name in the science news.  Her powerful voice is one we'll be hearing a lot more from.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Getting off the merry-go-round

Today's post is about the outcome of last week's election -- but a part of it you might not have heard about, given the media furore surrounding the race for president.

Last week Oregon became the first state to legalize psilocybin -- more commonly known as "magic mushrooms."

[Image licensed under the Creative Commons Arp, Psilocybe semilanceata 6514, CC BY-SA 3.0]

The change came about because of a pair of bills, Measure 109 and Measure 110, which (respectively) made the use of psilocybin legal in a therapeutic setting, including for reasons of "personal growth" (i.e. not to treat a specific condition), and decriminalized the possession of small amounts of a wide range of drugs, making it a minor non-criminal offense on par with a traffic ticket.  I'm not going to get into the second measure, by far the more controversial, except to say that Portugal did the same thing in 2001, diverting the money that would have been spent prosecuting and jailing drug users into treatment programs, and saw voluntary addiction treatment rates rise, and drug use amongst adolescents and deaths due to overdose both decline precipitously.

But passage of the psilocybin measure made me say, "About damn time."  Psilocybin was declared a "Schedule I drug" in 1970, meaning it was claimed to have "a high potential for abuse," "no currently accepted medical use," and "a lack of accepted safety."

All of which, in fact, turned out to be false.  It's non-addictive, rarely if ever causes deleterious side effects, and its efficacy for treating depression has been known for years.  Study after study has come out providing evidence that psilocybin works; so many that it's beginning to sound like the studies disproving the vaccination/autism connection, repeating the same protocol over and over, getting the same result, and saying, "SEE, WE TOLD YOU, IT HAPPENED AGAIN.  BELIEVE US NOW?"

In fact, just last week a study came out in the Journal of the American Medical Association showing that one or two administrations of psilocybin, in a controlled setting, triggered remission of the symptoms of treatment-resistant major depressive disorder for months, possibly years.

This kind of thing is a godsend, because the current state of treatment methodologies for depression resembles a blindfolded game of darts.  I went through three years of considerable hell trying to find an antidepressant that (1) actually mitigated my depression, and (2) didn't give me miserable side effects.  The frustrating part is that an antidepressant that works brilliantly for one person might not work at all for someone else, and no one knows why.  The first two I tried, citalopram (Celexa) and escitalopram (Lexapro), both made me sleepy and completely wiped out my sex drive.  The second one, lamotrigine (Lamictal) gave me thermonuclear-level acid reflux.  The worst was sertraline (Zoloft), which I know is a game-changer for some people, but made me feel like I was at the middle of a neural lightning storm.  I couldn't sit still, couldn't sleep, and couldn't stop out-of-control thoughts that included suicidal ideation.

I got off that stuff fast.

I was on the verge of giving up, but my doctor recommended trying one more, bupropion (Welbutrin).  Welbutrin doesn't give me side effects, which is kind of awesome.  I wouldn't say it erases my depression -- none of them really do that, pretty much for anyone -- but it blunts the edge of the worst of it.  On Welbutrin I don't have the crashing lows I used to get, and have experienced with clocklike regularity every four or five months for pretty much my entire adult life.

On the other hand, if psilocybin works for you (which it does for the vast majority), it works.  People report complete remission of symptoms, something I can't honestly imagine.  Best of all, it only takes one dose to get long-term positive effects.  

I take Welbutrin every day; for me it's a maintenance med.  The idea that I could take one dose of something and get off the merry-go-round of self-medication, to be able to throw away the little orange bottle I have to carry around with me when I travel, is incredibly appealing.

I find it somewhere between absurd and appalling that the government has dragged its heels on decriminalizing psilocybin and authorizing its use as a therapeutic.  Okay, fine, regulate it; allow it only under a doctor's orders and a doctor's care.  We can argue about whether recreational drugs should be legal another time.  But here we have something that could dramatically improve the lives of an estimated eighteen million people in the United States -- about seven percent of the population -- addressing the main reason for the sky-high suicide rate, averaging one person choosing to end his/her own life every twelve minutes.

Would I try it?

Damn right I would.  In a heartbeat.

I know whereof I speak about this.  I'm lucky to be alive.  I attempted suicide twice, ages seventeen and twenty, only pulling back from going through with it at the last minute out of fear.  I had another serious period of pretty much continuous suicidal ideation in my mid-thirties, and that time was saved by the knowledge of what it would have done to my kids.  I still struggle some days, but with the love and care of my wife and friends, and a medication that takes away the deepest lows, I'm on an even keel most of the time.  But the worst of what I've experienced I wouldn't wish on anyone, and it's unconscionable that our government is creeping along in addressing a disorder that is a direct contributor to the horrifying statistic that suicide is the second leading cause of death in the United States of people between the ages of ten and twenty-four, and the tenth leading cause of death overall.

It's time to start pushing our leaders into doing something, into following Oregon's lead, and into getting correct information to voters that "decriminalizing drugs" doesn't mean "encouraging everyone to become an addict."  That all current Schedule I drugs aren't the same -- lumping heroin, marijuana, ecstasy, and psilocybin in the same category is somewhere between scientifically inaccurate and downright idiotic.  That people with major depressive disorder should have a choice to try something showing tremendous promise not as a maintenance treatment, but something damn close to a cure.

Please write letters, make calls, get involved.  It could change lives.  Hell, it could save lives.  And I'll end with doing something I rarely do: ask my readers to share this post.  Link it, retweet or repost it, email it.  The word needs to get out there.

If we can get one person out from under the black shadow of depression, help one person to step out into the light, it'll be worth it.

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This week's Skeptophilia book-of-the-week is about our much maligned and poorly-understood cousins, the Neanderthals.

In Rebecca Wragg Sykes's new book Kindred: Neanderthal Life, Love, Death, and Art we learn that our comic-book picture of these prehistoric relatives of Homo sapiens were far from the primitive, leopard-skin-wearing brutes depicted in movies and fiction.  They had culture -- they made amazingly evocative and sophisticated art, buried their dead with rituals we can still see traces of, and most likely had both music and language.  Interestingly, they interbred with more modern Homo sapiens over a long period of time -- DNA analysis of humans today show that a great many of us (myself included) carry around significant numbers of Neanderthal genetic markers.

It's a revealing look at our nearest recent relatives, who were the dominant primate species in the northern parts of Eurasia for a hundred thousand years.  If you want to find out more about these mysterious hominins -- some of whom were our direct ancestors -- you need to read Sykes's book.  It's brilliant.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]