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.

*********************************

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!]

The power of relentless positivity

I have a friend whom I frequently take out for walks.  I'll call him Jim.  Jim doesn't have it easy; he's of normal intelligence but has a lot of serious developmental disabilities, and things that most of us don't even give much thought to -- brushing teeth, shaving, showering, changing clothes -- are time-consuming and arduous chores for him.  His only living relative is a five-hour drive away, so he is completely reliant on non-family members for his care.

Despite this, Jim is the single most positive person I've ever met.  Whoever coined the term "sunny disposition" must have known him.  Whenever we get together, he always tells me how much he appreciates my help and companionship.  At the end, he thanks me again, and says, "I had a lot of fun.  It was a good outing.  Thank you so much."

He also cares deeply about the people around him.  He always asks me how I'm doing, and unlike with some people -- for whom "how are you?" is a perfunctory and rather meaningless greeting -- Jim honestly seems delighted when I tell him what's going on in my life.  

He's like that about almost everything.  One Friday I told him I wouldn't see him till Monday, but I hoped he had a good weekend.

He gave me a big smile and said, "Gordon, I hope you have a great weekend more than you hope I have a great weekend."

Yesterday we went for a walk in Cass Park, a big, sprawling piece of parkland along the west shore of Cayuga Lake.  We'd only been out for a few minutes when Jim said, "It sure is a beautiful day.  Isn't it a beautiful day?"

For the record, at the time he said this it was about thirty degrees Fahrenheit, spitting snow, and there was a stiff breeze off the lake.  Here's a photo I took of Jim's beautiful day:

Okay, the Finger Lakes region of New York, where we both live, is pretty gorgeous even in midwinter, but I was immediately struck by the fact that no one I've ever met -- other than Jim -- would have characterized the day as "beautiful."  We were both well-wrapped with coats, scarves, and gloves, so we were comfortable enough, but it was still gray, chilly, and windy.

But for Jim, it really was a beautiful day.  For him, a beautiful day is a long walk with a friend out in the fresh air in a place he loves.  He's not impervious to discomfort; when we got back to the car, I turned the heater up, and he said, "That feels nice.  My hands are cold."  But what stands out to me is that Jim chooses to accept the discomfort because he appreciates what he has so deeply.

As we walked, it came to me that there was a descriptor for Jim: he's relentlessly positive.  There's nothing forced about it.  It's completely genuine.  He doesn't do it to be polite, or because it'll get me to come back and walk with him another day, or to make me feel good.

He's relentlessly positive because he chooses to focus on the beautiful things in his world rather than the (many) difficulties.

I wonder what it'd be like if more of us were like Jim.  Recognizing the problems we face and doing what we can about them, but first and foremost appreciating what we have.  As a lifelong sufferer of depression and anxiety, I know that telling a person "just be happy" is the opposite of helpful; and that's not what I'm saying.

What I'm saying is make the choice to look at the positive things first, and be grateful for them.  Make a practice of aiming for relentless positivity.

Jenny Lawson puts it differently in her amazing book Furiously Happy: A Funny Book About Horrible Things, which should be on everyone's reading list.  Lawson has struggled with serious, debilitating mental illness her whole life, and this memoir (and her first book, Let's Pretend This Never Happened) are the only books I can think of that made me ugly cry and howl with laughter, sometimes on the same page. 

Hell, sometimes in the same damn paragraph.

Lawson writes:

I’ve often thought that people with severe depression have developed such a well for experiencing extreme emotion that they might be able to experience extreme joy in a way that “normal” people also might never understand, and that’s what Furiously Happy is all about.  It’s about taking those moments when things are fine and making them amazing, because those moments are what make us who we are, and they’re the same moments we take into battle with us when our brains declare war on our very existence. It’s the difference between “surviving life” and “living it”... To all who walk the dark path, and to those who walk in the sunshine but hold out a hand in the darkness to those who travel beside them: Brighter days are coming.  Clearer sight will arrive.  And you will arrive too.  No, it might not be forever.  The bright moments might be for a few days at a time, but hold on for those days.  Those days are worth the dark.

It's like my walk yesterday with Jim.  There were probably people walking that same path in Cass Park yesterday who spent the entire time focusing on how miserable the cold is, how gray it all was, how a cold snap on the first day of April was a bummer.  Jim chose to look instead at the stark beauty of the lake under the gray clouds, the way the wind was making the fallen leaves tumble and rattle under our feet, how pretty the snowflakes looked swirling past our faces.

All of us were cold, out there in the park.  But some of us were cold and miserable; Jim was cold and relentlessly positive.  And I'm guessing that despite the continuous difficulties he lives with, he's the only one who got home and grinned and said, "Nice to be in a warm house again... but wasn't that fun?"

I'll end with one more quote from Jenny Lawson, that captures what I'm trying to say better than I ever could: "I see that there is dust in the air that will eventually settle onto the floor to be swept out the door as a nuisance, but before that, for one brilliant moment I see the dust motes catch sunlight and sparkle and dance like stardust.  I see the beginning and the end of all things.  I see my life.  It is beautifully ugly and tarnished in just the right way.  It sparkles with debris.  There is wonder and joy in the simplest of things."

*********************************

The sad truth of our history is that science and scientific research has until very recently been considered the exclusive province of men.  The exclusion of women committed the double injury of preventing curious, talented, brilliant women from pursuing their deepest interests, and robbing society of half of the gains of knowledge we might otherwise have seen.

To be sure, a small number of women made it past the obstacles men set in their way, and braved the scorn generated by their infiltration into what was then a masculine world.  A rare few -- Marie Curie, Barbara McClintock, Mary Anning, and Jocelyn Bell Burnell come to mind -- actually succeeded so well that they became widely known even outside of their fields.  But hundreds of others remained in obscurity, or were so discouraged by the difficulties that they gave up entirely.

It's both heartening and profoundly infuriating to read about the women scientists who worked against the bigoted, white-male-only mentality; heartening because it's always cheering to see someone achieve well-deserved success, and infuriating because the reason their accomplishments stand out is because of impediments put in their way by pure chauvinistic bigotry.  So if you want to experience both of these, and read a story of a group of women who in the early twentieth century revolutionized the field of astronomy despite having to fight for every opportunity they got, read Dava Sobel's amazing book The Glass Universe: How the Ladies of the Harvard Observatory Took the Measure of the Stars.

In it, we get to know such brilliant scientists as Willamina Fleming -- a Scottish woman originally hired as a maid, but who after watching the male astronomers at work commented that she could do what they did better and faster, and so... she did.  Cecilia Payne, the first ever female professor of astronomy at Harvard University.  Annie Jump Cannon, who not only had her gender as an unfair obstacle to her dreams, but had to overcome the difficulties of being profoundly deaf.

Their success story is a tribute to their perseverance, brainpower, and -- most importantly -- their loving support of each other in fighting a monolithic male edifice that back then was even more firmly entrenched than it is now.  Their names should be more widely known, as should their stories.  In Sobel's able hands, their characters leap off the page -- and tell you a tale you'll never forget.

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