Folie à deux

One of the long-standing unanswered questions in medical science is the role of the mind in physical health.

A well-known example is the placebo effect, the reduction or elimination of symptoms in an ill person from taking a "medicine" with no active ingredients.  Less known, but also well documented, is the nocebo effect, where someone believes they will come to harm, often from supernatural means -- as in voodoo curses -- and then actually does.  (Placebo and nocebo come from Latin, and mean "I will please" and "I will harm," respectively.)

The mechanism by which this could occur is poorly understood at best.  We do know that in situations of high emotional or mental stress, the body produces hormones like adrenaline and cortisol, which can have long-term deleterious effects (thus the connection between stress and inflammatory diseases), but it seems like there must be more to it than that.

And that's not even as complicated as it gets.  Consider, for example, folie à deux -- also called shared psychosis -- when two people experience the same strange delusions.  How this happens and the mechanism by which it works are unknown, and the results can be nothing short of bizarre.

[Image is in the Public Domain courtesy of its creator, Chitrapa]

The best example I've ever heard of folie à deux is the case of June and Jennifer Gibbons.  The two were identical twins, born in 1963 in Yemen to British subjects originally from Barbados.  By 1974 the girls, their parents, and three other (completely normal) siblings were living in Haverfordwest, Wales, where their father worked as a Royal Air Force technician and their mother was a homemaker.

The twins started exhibiting odd behavior as toddlers.  They rarely spoke except to each other, and their conversations were conducted in a largely invented language based in part on a sped-up version of Bajan Creole.  (Siblings inventing their own private language isn't that uncommon, and is called idioglossia; but here, the twins seemed entirely unwilling to speak in English, nor to anyone but each other.)

The parents, and the girls' teachers, tried everything they could think of to break this strange link.  Sending them to separate boarding schools completely backfired; both girls became catatonic, refusing to eat or move until they were reunited.  The one way they would let anyone else know what was happening in their minds was through writing.  Given a gift of diaries when they were sixteen years old, they began writing elaborate stories -- but filled with violence and disturbing imagery.

In 1981, following a string of petty crimes they were accused of, the twins were committed to Broadmoor Hospital, where they were eventually to spend twelve years.  And this is where things took an even more peculiar turn, because they told the staff at Broadmoor that the only way one of them would live a normal life is if the other died.  It didn't matter which; to break the spell required one of them to die, after which the other would go on to speak, act, and live normally.

In 1993, they were transferred to Caswell Clinic in Bridgend, Wales, and upon arrival, Jennifer was found to be unresponsive.  She was admitted to the hospital where she lingered, comatose, for a week, but finally died due to what an autopsy found to be acute myocarditis (inflammation of the heart).  Strangest of all, there were no drugs, poisons, or infectious agents in her system that could be found to explain the illness, and the inquest ended with a finding of "ultimate cause of death unknown."

A week after her sister's death, June told a therapist, "I'm free at last, liberated, and at last Jennifer has given up her life for me," and described the moment of Jennifer's death as hitting her "like a tsunami."  She was monitored by psychiatric services for several years, but eventually was discharged, because -- exactly as the sisters had predicted -- the survivor had begun living an entirely normal life.  By 2008 June had a flat near her parents in a small village in western Wales, and was working and socializing like any ordinary person would.

What on earth could have caused this bizarre situation?

The simple answer is "we have no idea."  There is nothing in what is known of the Gibbons family's background that could account for it; judging by statements from the twins' siblings, they seem to have been a completely ordinary working-class family.  Strangest of all is the circumstances that severed the connection between Jennifer and June.  Did Jennifer Gibbons actually "will herself to die" to free her sister, or was there something more sinister going on?  What was the nature of the link between them -- and how can we account for the medical and psychological manifestations of it?

Once again, there are no clear answers.  We're left with more questions -- particularly, how the mind creates the world of perception we live in, and how it can go so drastically wrong for certain unfortunate people.  The treatment of psychiatric illness is certainly far better than it was even forty years ago, when the Gibbons twins started their decade of life in Broadmoor, but we're still largely in the dark about how the mind works -- and how it can so profoundly affect the body in which it resides.

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The merry-go-round of self-blame

Depression is, at its heart, a completely irrational condition.

One of the (many) therapists I've seen during my life told me that the way to deal with depression and/or anxiety was to do a reality check.  Is this feeling I'm having right now consistent with what I know reality to be?  It sounds good, but in practice, it's extraordinarily difficult to do.  Depression and anxiety make it harder for you to be certain what reality is.  The problem is that the depressed and/or anxious response feels just as real as reality does.  You can analyze those feelings in as dispassionate a way as you want, but when the things you're trying to discern seem to be equally plausible, you're in trouble.

One good example is my continual fear of talking too much or calling attention to myself in social situations, especially when I've had a drink or two.  If I'm stone-cold sober there's usually no question, because I hardly ever say anything, much less too much or the wrong thing.  But the inhibition-releasing tendency of alcohol consumption blurs the ability to self-perceive accurately, and afterward, I'm always convinced that I said more than I should have or something I shouldn't have, and nearly every time I have to appeal to my wife to do my reality checking for me.

This is why my reaction to a piece of research that appeared last week in the Journal of Psychiatric Research made me say, "Well, duh."  Not, understand, that I am at all critical of research to support what are honestly anecdotal claims; more that what they found is essentially how I live.  A team at King's College London, led by clinical psychologist in mood disorders Roland Zahn, studied the reactions of a group of test subjects -- some of whom had a history of suffering from depression, and others who did not -- to various hypothetical social interactions, and had them identify what would be their most likely responses if it were a real situation.

[Image licensed under the Creative Commons Sander van der Wel from Netherlands, Depressed (4649749639), CC BY-SA 2.0]

What the team found was that people who have depression tend to blame unpleasant social interactions on themselves, even if the circumstances make it unlikely that they were at fault.  "Self-blaming feelings such as guilt, self-disgust and self-directed anger are key symptoms of depression and Freud is widely credited for pointing to the importance of excessive self-blame in depression," Zahn said, in an interview in PsyPost.  "Social psychologists have done research into these so-called ‘action tendencies’, i.e. implicit feelings of acting in a certain way, such as hiding or creating a distance from oneself, which are entailed in complex feelings.  This is why my PhD student Suqian Duan set out to investigate this question.  In this study, we investigated blame-related action tendencies for the first time systematically in people with depressive disorders."

The response Zahn describes is strikingly similar to my experience of clamming up completely in social situations.  "Many people with a history of major depression, despite having recovered from symptoms, showed an action tendency profile that was different from people who had never experienced major depression and are thus at a lower risk of depression overall," he said.  "They were more likely to feel like hiding, creating a distance from themselves and attacking themselves when faced with a hypothetical scenario of acting badly towards their friend whilst being less likely to apologize.  Interestingly, we showed that the label of the emotion did not map one-to-one on specific action tendencies as was often assumed but rarely tested.  Feeling like attacking oneself was specifically associated with self-disgust/contempt, a feeling which we had previously found to be the most common form of self-blaming feeling in depression."

Zahn points out (correctly) that one of the difficulties is there is such a thing as reasonable guilt.  Purging oneself of all guilt feelings shouldn't be the goal; sometimes we feel guilty for a very good reason, and those feelings can prompt us to make amends for mistakes we've made.  "There is... a controversy around how to measure and define healthy forms of guilt, which help us to apologize and try to repair the damage we might have done from unhealthy forms of self-blame, where we take responsibility for things that are out of our control and feel paralyzed by our guilt or sense of failure, so that we hide away from the situation," Zahn explains.

The trouble is, with depression and anxiety, the ability to discern between justified and unjustified guilt or self-blame gets blurred, and depression and toxic narcissism lead to opposite and equally damaging false conclusions; the former, that every negative interaction is our fault, the latter that none of them are.

It's hard to see, in the absence of someone like my wife to do an external reality check, what you could do to get off the self-blame merry-go-round.  When the heart of the problem is an inaccurate but compelling view of oneself and the situation, trying to do any kind of internal reality check is likely to meet with limited success.  That's certainly been my experience.  I can even go into a social situation with the mantra, "I know I don't talk too much, everything is going to be fine, I should loosen up and just chat with people," but afterwards the inclination to self-blame anyhow is awfully powerful.

No wonder we feel like hiding a lot of the time.

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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!]

A pandemic of isolation

When the pandemic started, and I first realized what the implications were, I thought the effect of it on me personally was going to be less than it has turned out to be.

I'm retired from my day job, and now am a full-time writer.  So even before the lockdown started, on a typical day I'd spend most of my time in my office.  (I was going to say "most of my time writing," but given how distractible I am, it'd be closer to the truth to say, "most of my time futzing around on social media and feeling guilty because I'm not writing."  The struggle is real.)  My social life consisted of gym nights with my pal Dave, weekly critique sessions with my writing partner Cly, and the occasional dinner out with my wife.

So I figured, "hey, I'm an introvert anyhow, this isn't going to change my day-to-day life much."

I was wrong.

The social isolation is really getting to me, and has been for some time.  Part of it, of course, is that now I can't socialize with people even if I want to.  I've tried to work in some socially-distanced visits; Dave and I do the occasional hike on a local trail, and I still meet with Cly on her front porch for our critiques, once every three weeks or so.  (What we'll do when the weather turns cold -- which in upstate New York could be by the end of September -- I have no idea.)

But it's been hard.  I miss people.  I miss being able to travel.  I was going to sign up for a three-week retreat in Thailand in January 2021 led by John Aigner, who led the transformative weekend retreat I attended last November (and about which I wrote here), but due to the piss-poor response our country's leaders had to the pandemic, there's now what amounts to a barrier around the United States preventing any of us from leaving and infecting the rest of the world.  (Donald Trump wanted a wall.  Well, he got one.)

I know in the grand scheme of things, this is all minor stuff.  First-world problems, you know?  And honestly, I'm fine with making these sacrifices to slow down the spread of this horrible disease.

But I'd be lying if I said it hasn't affected me.  And I'm not alone.  Research published this week in the Journal of the American Medical Association found that since the pandemic started, the rates of depression in the United States have tripled.  The increase, unsurprisingly, is higher amongst people with low income, who are not only facing the social isolation but fears of medical bills, loss of jobs, threats of eviction, what to do about their children who are now staying home from school when they can't afford daycare, and being in a situation where just to survive they have to expose themselves and their families to illness.  The effect, though, was there regardless of demographic.

[Image licensed under the Creative Commons Sander van der Wel from Netherlands, Depressed (4649749639), CC BY-SA 2.0]

We're social primates, and a strong social context is important even to us introverts.  A study published this week in Nature Neuroscience looked at the effects of early social isolation in mice, and found that being alone caused an inhibition in activity in the neurons that link the prefrontal cortex to the paraventricular thalamus -- known to be part of the reward circuitry active in adults.  While the research could lead to targeted medical treatments for psychiatric disorders impairing socialization, it immediately made me wonder whether this could be at the heart of the spike in depression we're currently seeing.

Because that's part of what I'm experiencing in my own behavior since the pandemic started -- less activity in areas where, prior to the lockdown, the primary reward was dependent on socializing.  Now that I'm not hitting the weights at the gym three times a week with Dave, I haven't been using my home weight bench nearly as much.  I don't have Cly expecting me to have a chapter to read every Tuesday night, so I've been writing way less.

It's been an interesting exercise in self-examination to find out that basically, I'm extrinsically motivated.  When I'm at home alone, and no one is expecting me to get my ass in gear and write something on my work-in-progress or get my gym gear together and head on down to lift for a couple of hours, it's way easier just to say "I'll do it later" and go back to the inevitable focus on the news and social media.  I do have some pastimes I've kept up with -- I'm an amateur potter (not all that good at it; in my hands it's more "playing in the mud for adults") -- and I still hit the wheel three or four times a week.  But it's kind of astonishing to me now that I have more free time, in that I'm no longer teaching eight hours a day, I actually spend less time engaged productively.  And I think a lot of that has to do with the aimlessness that comes from being adrift, on a typical day having no contact with anyone but my wife.

Zoom and Skype and social media only take you so far.

Put simply, I -- and lots of people like me -- are lonely.  It's a hard time for everyone, but I think we can't discount the emotional toll this is taking on ordinary, average people.  There are a lot of jokes going around about how once the pandemic is over, we'll all be celebrating with drunken orgies, but the truth is, I think it's going to take us a long time to recover our equilibrium.

Like I said earlier, I'm still completely willing to make these sacrifices for the common good, and I think the people who are flouting the rules and getting together in large groups anyhow (or people like Florida's governor Ron DeSantis who have steadfastly refused to mandate wearing masks) are simply assholes.  But the fact remains that a lot of us are struggling.  So check in on your friends and family, even the ones for whom it's easy to say, "Oh, well, (s)he's an introvert, I'm sure (s)he's fine."  We need to be kind to each other in these times, and to understand that the illness itself isn't the only concern.

And take care of yourself, okay?  We need all of you to stay happy and healthy and whole through this.

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This week's Skeptophilia book recommendation of the week should be in everyone's personal library.  It's the parting gift we received from the brilliant astrophysicist Stephen Hawking, who died two years ago after beating the odds against ALS's death sentence for over fifty years.

In Brief Answers to the Big Questions, Hawking looks at our future -- our chances at stopping anthropogenic climate change, preventing nuclear war, curbing overpopulation -- as well as addressing a number of the "big questions" he references in the title.  Does God exist?  Should we colonize space?  What would happen if the aliens came here?  Is it a good idea to develop artificial intelligence?

And finally, what is humanity's chance of surviving?

In a fascinating, engaging, and ultimately optimistic book, Hawking gives us his answers to the questions that occupy the minds of every intelligent human.  Published posthumously -- Hawking died in March of 2018, and Brief Answers hit the bookshelves in October of that year -- it's a final missive from one of the finest brains our species ever produced.  Anyone with more than a passing interest in science or philosophy should put this book on the to-read list.

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