“Science Belongs to Everybody”: A conversation with
neuroscientist Richard G. Hunter, PhD (Part 1)
“That is the essence of science: ask an impertinent question, and you are on the way to a pertinent answer.”
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In late September, I went down a PubMed rabbit-hole searching for information on epigenetics, glucocorticoids, and SNPs (single nucleotide polymorphisms) just because. That led to my first-ever science research article purchase and, more specifically, to the work of Richard G. Hunter, PhD.
I highly recommend reaching out to neuroscientists. Not only are they engaging, thoughtful, and founts of info-packed sentences, they may also give access to research articles for your nerding-out reading pleasure. Richard kindly agreed to speak with me about his work, about epigenetics, and — well, you’ll see. No spoilers!
Last Friday, I spoke by phone with Richard — he in New England, I in the San Francisco Bay Area — and it’s probably one of the more interesting conversations I’ve had all month (all year?). I ended the conversation with 10 questions that James Lipton (yes, he of the Actors Studio) asks every guest.
Thank you, Richard! This was much fun.
Topics of conversation: neuroepigenetics; epigenetics; schizophrenia; stress research; animal models; ethology; Orphan Black; Jonah Lehrer; “life-ectomy”; antidepressants; SSRIs; experts should just keep their eyes on their own plates; qualitative data; rats; mice; eusociality; naked mole rats; mammals; neurogenesis; Head Start; early childhood development; healing; inspiration; trust; brain damage; hippocampus; amygdala; PTSD; chronic social defeat; graduate school; life; history
Sometimes I write to random people, people whose work I find interesting —
— and sometimes I interview them, so thanks for being open to my asking you random questions.
You, in your professional life, do the kind of work that I read about for fun. I think it’s really important work. And I feel like … I wish more people were aware of the kind of work that you and your colleagues are doing.
Yeah, I would say particularly my colleagues. I’m not sure what kind of contributions — I mean, I think I’ve done some interesting stuff. But the stuff you mentioned, like Richard Anda’s work and Michael Meaney’s research, is pretty significant, and does deserve a lot more play than it gets. Because if you think about something like child abuse, it’s probably one of the biggest contributors to public health negative outcomes in developed societies, period. But it’s completely unreported and unrecognized. You know? We pay a lot more attention to things that affect a lot fewer people.
How did you come to research neuroepigenetics and psychology?
Well, my actual training is as a pharmacologist. And I got into that, I come from a family with a lot of medicine in it — my dad’s a neuropsychiatrist, so the brain stuff came to me early and easy. But I, in college, I spent some time, dropped out of college actually for a while, [and] worked as an orderly in mental hospitals. I was really struck by the amount of people really suffering there, the relatively small investment that our society makes in their care, and the fact that the drugs we have are — at that time and still to this day, particularly for psychosis — not much better than a physical lobotomy.
They are better, but they’re still not great — they have horrible side effects when they’re used long-term. I got a PhD in neuropharmacology, and I got interested in stress [studies] in graduate school and that’s where I did my postdoctoral work with Bruce McEwen, who’s the fellow who trained Mike Meaney [Michael Meaney, PhD] a long time ago, and Robert Sapolsky. So, in good company in terms of who I trained with. Although, obviously, they’re a lot more accomplished guys than I am.
But I’ve just always been interested in that. I wanted to know why things in your life affect you, why life events have the lasting impacts they do. I mean, there’s sort of an obvious intuitive reason why something horrible happening to you can affect you, but some people it doesn’t, and some people it does. So I guess that curiosity’s driven it.
Yeah, [Robert] Sapolsky did his graduate work with him. [Michael] Meaney did his post-doc with him. And he’s [Bruce McEwen] pretty much trained everybody who does stress neurobiology or they’ve been trained by somebody he trained. At some point for his 70th birthday I did a family tree and it’s basically everybody who’s done work in that area, so he’s kind of the great-granddaddy of all kinds of stress neuroscience research.
He started back in the late ‘60s with the discovery that there were steroid receptors — specifically steroid receptors for stress hormones like cortisol and corticosterone — in the brain, and has been contributing ever since. [The McEwen] lab was one of the first labs to show that dendrites on neurons change structure in response to things like stress and estrogen.
One of the first labs to show — in mammals — that there are new neurons being born in the brain, particularly in the hippocampus, and the rate of that is influenced by stress. So it’s a pretty storied lab. Sapolsky’s foundational work was done when he was a graduate student in Bruce’s lab. So he’s of great eminence in the field.
Could you tell me more about working as an orderly? Why did you drop out of college?
I didn’t know what the heck I was doing, and got crappy grades, frankly! [Laugh] I mean, I think that I just had got — I was a very smart kid in high school and I got good grades without ever trying and then I got out and into college, and had an easy time with the intro classes. And then I blew off my sophomore year classes and didn’t do so well so took some time off to re-assess. And partially because of my dad’s connections, and partially because of curiosity, I wound up in a job at a mental hospital, which turned out to be a very interesting job and had a lot of influence on the way I think about things even now.
There was never a dull day, that’s for sure. I was the smallest orderly actually, I think at the whole state mental hospital, so I had to get very good speaking skills and cultivate a calm demeanor, which was helpful, I guess. [Laugh]
What was your experience [at the state mental hospital] like, as an orderly?
It was a number of things. The patients are largely schizophrenics and often are very sympathetic people — when they haven’t decided that you’re part of their delusional process. They’re noted for being very kind and straightforward people when they’re not actively psychotic and so there’s a very sympathetic population that — a lot of them had lived on the street and been subject to all manner of abuse. Many of them had acquired multiple diseases. We had one patient I recall who had syphilis, tuberculosis, and HIV simultaneously from living on the street, from being raped.
It’s a population of people who we happily ignore in most of our lives and I was really struck by it and I still hope to be able to help that group of people. And there’s an overlap with that group of people — not just schizophrenics, but people who suffer from profound depression, PTSD, and really severe mental illnesses — that we don’t have much to do for. And so that motivates, that’s the underlying motivation to my intellectual curiosity about looking at how does the brain build these responses, some of which are so horribly maladaptive.
But it was, yeah, it was a very interesting place to be. I had a lot of interesting interactions because my job was basically to take people’s vitals, their blood pressure, check their weight, and then sit with them out in the dayroom eight or nine hours a day. I’d sometimes drive them to appointments and stuff like that, so I spent a lot of direct time with people who were pretty profoundly disturbed that, yeah, it stayed with me.
I’m reminded of the work that Gabor Maté does in [Vancouver, British Columbia’s] Downtown Eastside. He’s a Canadian physician and — are you familiar with his work?
The name sounds familiar, but you probably know more about him than I do.
He works with the Coast Salish people in British Columbia. This may be apocryphal, but he was a high school English teacher and then he decided to go to medical school and dedicated his work to practicing harm reduction but then also working with the First Nation population of Downtown Eastside in Vancouver, where there are a lot of people with addiction and people doing sex work. He talks about the history of trauma, intergenerational trauma, of being First Nation and then the ramifications —
Oh, there’s — both in Canada and in the U.S. — the first Americans or First Nations people as you have it, there’s horrible addiction and horrible intergenerational trauma and abuse. Yeah, you’re talking about another largely ignored population. That is certainly one of them.
Maybe you already answered this question, but what drew you to your current field of study? It sounds it had to do with taking that path where you decided that college wasn’t for you at that point and getting a job working as an orderly. When did you know that this was what you wanted to pursue as a graduate student, for a career, that you wanted to dedicate your life to learning and teaching?
I think it took me a longer time to intellectually come around to it than it did emotionally. When I was in college I sent out a bunch of snail mails — because this was the ‘90s and email wasn’t that common yet — to various scientists around Atlanta, which is where I was from. Tom Insel [Thomas R. Insel, MD, the N.I.H. Director] — who’s now the director of N.I.H. and, at the time, was head of the Yerkes Regional Primate Research Center — was one of the few people who responded to me.
He had me come in and talk to him, and apparently I was impressive enough that he told me to go talk to this guy that they were about to hire who wound up being my PhD mentor[, Michael J. Kuhar, PhD]. And I worked with him as a technician for a couple of years before doing my PhD with him. In the course of that time I figured it out, even though I think I was already on the course then? I think I had to get past the whole medical school thing, because my brother, step-brother, and dad are all MDs, and so I was like, “Well, I guess I should do that.”
And in the course of being a technician and putting out applications to both grad schools and med schools, I took the MCAT, and got a much better score than anyone in my family ever had, and then suddenly I was like, “Wait. Now that I know I can do this” — you know, of course, the bad grades — “I don’t wanna. I really actually like this science stuff.” So, that’s what I did. I thought, “Now that I know that I can do this, I don’t want to do it, so I’m going to be a scientist because that’s what I’m doing anyway,” because I have wandered into this perhaps on purpose. My unconscious was well ahead of my conscious, as far as that decision went.
So, yeah, the rest is history. That was my vocation. I know the way people talk about being a priest or whatever, you have that moment where they’re just like, “Oh, this is what I should do.” And that was kind of my experience of deciding, finally, “Oh yeah. I’m kind of a scientist, aren’t I? Well, maybe I’ll just stick with this.” [Laugh]
How old were you when you took the MCAT?
I was 25, so it was a little late because college took a little longer than normal. I picked up the review text at Kaplan or whatever put it out, read it three times, and then did really well, and then I was like, “Well, okay, this isn’t that hard!” [Laugh]
Yeah. So. I think it actually is harder. To be fair. [Laugh]
[Laugh] Yeah …
I got lucky. Actually, I got lucky in two ways in that I probably prevented myself from making a decision that I probably would have been a lot less happy with.
Did you do your undergraduate studies at Emory University? Is that right?
No, I did my undergrad at University of Texas at Austin, and then did my PhD at Emory University.
There’s a woman whose work I discovered from a talk she gave at the University of Pittsburgh, where she spoke about the link between depression and early childhood trauma. Her name is Christine Heim, and I wondered if you ever interfaced with her there [at Emory University]?
No, I haven’t interacted with her directly. I read her stuff on occasion. She’s pretty good. But, yeah, I haven’t. She’s at Pitt, you say?
No, she gave a talk there, which I downloaded [from the Internet] a couple of years ago, but she was at Emory. She was teaching at their medical school, but I think she’s moved on. I think she might have gone back to Europe. She’s from Germany.
I think she was there — I think she basically came into Emory right after I left grad school and went to post-doc in New York and then she left. Emory had a big cycle through, briefly, of psychiatry faculty right around the time of the [economic] downturn because Emory was one of these universities that put a ton of money into building new facilities when the N.I.H. was doubling funds all the time.
Since then, the N.I.H. basically has been — as you probably know — it’s been hammered funding-wise for the past 10 years. When that [funding] collapsed, a lot of the support for these new faculty [members] collapsed. So I think that what happened with her was that she was there for a few years and then probably went back when the funding here got horrible.
But yeah, she does good work. She actually works with a couple of people I do know: Elisabeth Binder, who’s also in Germany, and Kerry Ressler, who’s at Emory now, but who’s about to come and be the Chief Science Officer at McLean [Hospital] here in Boston. And Kerry’s work is pretty incredible.
I don’t know if you, in the course of your readings, have been seeing it, but he and Elisabeth have a paper that came out last year where they basically showed that the gene expression patterns and the DNA methylation patterns between people with PTSD who have no history of childhood abuse and people who have a history of childhood abuse who have PTSD, basically they constitute almost completely separate patterns.
In other words, those are two biologically distinct forms of the disorder, which is profoundly significant because this is one of the first times that biology has actually been able to say, been able to come down and provide evidence, that something that exists as this kind of DSM checklist entity actually has biologically distinguishable subsets.
Usually we subdivide it as, “Well, he’s a paranoid schizophrenic,” or, “He’s” — what used to be called a hebephrenic, but now it’s called — “[a] disorganized-type schizophrenic.” But there’s no real biological basis for distinguishing between a paranoid schizophrenic and a disorganized-type. It’s just all, “Well, he looks disorganized,” or, “He’s paranoid.”
The biology just isn’t there but now, thanks to stuff like what Kerry’s been doing, there’s an evolving biology for some of these things that might allow us to actually start to generally work on understanding them because we’ve gone through a period, over the past 30 years with the whole “chemical imbalance” hypothesis — which I think has deeply misled us and we … well, it was kind of this attractive nuisance, as they say in the legal profession. [Laugh]
Because it’s a really simple idea and it’s very appealing, and it kind of fit with the fact that a lot of these drugs that did seem to have some effect — like antipsychotics or tricyclic antidepressants — they affected certain discrete classes of receptors in the brain. It fit with that data, but we got it ass-backwards. As you know, we never really proved that there was a lack of serotonin that depressed people, for instance.
And so we spent a long time building animal models of things, which maybe don’t really exist biologically in people, or in animals —
— um, and —
Yeah. I mean, this is the problem with science: that, as Einstein said, if we knew what we were doing, we wouldn’t call it research! [Laugh]
But sometimes it’s a little difficult to admit that that’s really what’s happening. But I think that there’s been a lot of re-assessment of that hypothesis over the past five, 10 years, and we’re kind of coming back around to doing much more basic stuff and stepping away from our pre-conceptions. And hopefully that means there’s going to be a big move forward and we’re going to get real biology out of this stuff.
But that was a long digression. [Laugh]
That’s okay! [Laugh] Do you consider yourself — so you teach in the, you’re Assistant Professor of Psychology: do you consider yourself a psychologist? A psychopharmacologist? How do you self-identify in terms of the kind of scientist that you are?
I just say I’m a neuroscientist because I’m trained in, my post-doc was in, neuroendocrinology, my PhD’s in neuropharmacology, and now I’m in a psych department. I’m a neuroscientist and sometimes I might say that I’m a neuroepigeneticist, but, you know — [Laugh]
Keep it simple.
— basically neuroscientist fits. It covers most of what I do, at least in my workaday life. [Laugh]
The field of psychology is becoming more interdisciplinary because of these cross-[disciplinary] conversations. Has that always been the case? Or do you think it’s new since new research has been coming out?
I think it’s relatively new. I mean, obviously, I haven’t been around for long enough to comment on psychology since Freud!
But I think it has become more interdisciplinary. I think there was a long time when, say, neuroscience was resisted within psychology departments. It was viewed as too reductionist and biological, but it’s becoming apparent that a lot of this stuff really does have a biological component. And, on the other side, I think because of things like I was just talking about, the heavily biologically-reductionist people are sort of admitting that, “Hey, maybe it’s a little more complicated than this. Maybe it’s not just serotonin.”
Because, if you actually sit and look at people, which is a problem for a lot of research folks — myself included — I mean, I’m lucky in that my dad’s a psychiatrist so I can talk to him and that I have the experience I did actually working with the mentally ill, but a lot of my peers have never actually interacted directly with someone who’s been hospitalized for a mental illness.
And so they’re building models of it, and they’ve never seen it. So it’s something that I think people who are thinking about it recognize really needs to happen, but there remain some disciplinary boundary issues and turf stuff, because the different disciplines — the different sub-disciplines — have very different rules about how they operate. Neuroscientists, we like to … obviously we lead with the science part, and so we’re not as concerned with being advocacy-oriented as, say, someone in psychology might be.
But I think, yeah, that’s the general trend, is to be much more integrated, which is a good thing.
So, just as a human being — [Laugh]
— what’s your take on … so you work with data —
— and you work with large amounts of data, analyze it, and figure out what that data suggests, and you start out with a hypothesis, all these things. But, as a human being, what is your — and you kind of alluded to this with the clinical versus research tension.
I think that’s a false dichotomy. But in terms of qualitative data that you collect, what is its function, or how should qualitative data [be taken into account]? What about the elisions or gray areas? I know that you said that, as scientists, scientists don’t really do advocacy per se, and then there are differences in terms of reductionism. How do people’s stories factor in [to their mental and other health]? It sounds like you’re deeply aware of people’s histories and that history’s effect on their health — mental and otherwise — based on your work as an orderly. Basically, I am trying to ask: Do you care about qualitative data? Why or why not? [Laugh]
History is an important thing to me. Before I started majoring in biology in college, I was a medieval history major, and history is still something I do recreationally, so to speak. And it certainly influences my interest in stuff like epigenetics, because epigenetics is kind of the biological record of an organism’s history, you know? A single organism, as opposed to a species, and obviously I think that’s significant, otherwise I wouldn’t be researching it.
Qualitative data is kind of a broader question, but it’s not an insignificant one. It’s just, within the kind of neuroscience I do, it’s not something that comes up much, other than when you’re doing ethological models. I think it’s something you need to pay attention to, and I think it’s something that, actually — particularly when you’re trying to model things like mental disorders — you need to attend to the ethological context of the species you’re using.
You know, rats and mice are not tiny people. In fact, mice are not even small rats. Mice and rats have very different biologies, they have some organ differences, [differences in] brain structure. Mice are kind of, uh … they’re horrible.
Rats are kind of sweet. [Laugh] I might have some prejudices. That’s not my scientific opinion! But, yeah, you have to pay attention to what the species do. Mice are completely asocial, rats are medium-social, for mammals, and then humans and naked mole rats — and some primates — are highly social, as mammals go. Naked mole rats are probably more social than we are, really, certainly, because they’re eusocial. They’re like ants in the way they have their social system organized.
And so you have to attend to that, and you have to attend, also, to the context of humans. I think that, in my discipline, it’s something that you are paying attention to as a matter of designing the right kinds of experiments and bringing caution to how you interpret stuff.
Beyond that I think it’s an interesting thing because I do believe that scientists have to be very careful about being advocates in the political sense because science by itself has a value that is fairly fragile and easily endangered when it becomes associated with too much of one side of an argument. I think that you’re seeing that right now with climate science, where there’s a group within the U.S. who’s decided, “Well, because climate scientists consistently come down and call us stupid, that maybe we don’t believe in science.”
And it’s not entirely on climate scientists, but it is a part of the kind of advocacy — looking back at Paul Ehrlich, where he basically just started screaming at anyone who didn’t agree with him and called them idiots. You don’t want to alienate half of society to science. Science belongs to everybody.
Right? Which is not to say that you need to tolerate all the idiots in the world —
— but I do think you need to be cautious. Because often scientists — Paul Ehrlich being a good example — have a great degree of certainty or they think they do, about their own discipline and they try to extrapolate it into areas where they don’t actually have that much experience. And we know from the science around expertise that experts really tend to not be very good outside of their field.
If you start bringing the weight of your expertise or say, “I have a PhD, and I have a professorship at Berkeley,” or whatever, “You’re obviously dumber than me.” Even if I don’t have a PhD in that, you’re doing some damage to science and you’re doing some damage to the discourse because you really don’t have the right to be saying that because you don’t understand it any better than a man on the street does, typically.
So I have some caution about that. But as far as the issues that I’ve been concerned with, and where that touches on public policy, things like child abuse and things like that, I think that I have a responsibility to report the facts and that is that something like a sixth of the population has four or five or more of Anda and [Vincent] Felitti’s ACEs [Adverse Childhood Experiences], which increases their risk of suicide attempts 300-fold, and — I.V. drug use by 40-fold. Liver disease, heart disease. Your changes of marrying an alcoholic go up by three-fold.
You’re more likely to be crushed by a vending machine than getting bitten by a shark. Statistically speaking.
It’s just all of these things go up with that, and we have no structured advocacy for that anywhere in our society right now. It’s starting to slowly happen. But we pay more attention to things like shark attacks than we do child abuse, and sharks kill less people than vending machines do, you know? Literally.
Vending machines! Is that what you just said?
Yeah, you’re more likely to be crushed by a vending machine than getting bitten by a shark. Statistically speaking.
I love that [stat]! Oh my god. Who knew. So. Longitudinal studies: your thoughts.
Well, I think we need them. The problem with them is that they’re hard to do and they require a kind of dedication to something beyond your immediate career that is hard, frankly, in small, low-funding times, because if you want to do a good longitudinal study, you have to basically build something that’s going to last longer than you are or, at least, than your career is. So I think there are some internal structural problems with them, but, yeah, we need them.
Stuff like Anda and [Simonetta] Fraschetti’s work, stuff like [the Framingham Heart Study], ABCD [Adolescent Brain Cognitive Development Study], and all of these early childhood intervention studies — for instance the Perry Child Health Project [the HighScope Perry Preschool Study] — that have been going on now for decades, and where we’re able to look at what the sequelae of these interventions are. That’s the only way we’re going to find out what works with people.
I mean, I work with rats and one of the reasons we work with rats is that they live two years and they have babies every three months or less. And so you can accelerate that kind of time process and look at these life course, intergeneration, generational effects in a time that somebody like me, I can see that before I retire.
But for science at large and for really understanding how that affects the human condition — because humans are kind of unique animals — we have to do these things. Because we get people aren’t rodents. There are inferences you can build from them, but — and you can build hypotheses that you can apply to human experience off of rodents and off of monkeys, but you still have to test that hypothesis on people, and longitudinal studies are the only way to get at it for some of these questions.
So, we need them. We probably need more of them.
This might be repetitive, but tell me your thoughts on how neuroscience and psychology interface.
Well, I think now neuroscience lives in a place between psychology and biology. I get comments from the biology department, “Well you should be in our department!” and I’m sort of considered — within my department — to be the most biological. So we’re kind of in the interstices and some universities have kind of built it out so that there’s a separate neuroscience program that operates between multiple departments.
Neuroscientists, by nature, we’re very interdisciplinary so we kind of extend into some space where psychology usually doesn’t tread. And psychology is often off in spaces where we don’t exist, too. I think that there’s a lot of fruitful interaction there, but both areas are very broad and there are parts that don’t talk that much.
Social psychology doesn’t interact very much with social neuroscience, but I think that that’s something that should probably change. I think the more clinically oriented disciplines are much more likely to interact, just because a lot of the funders and a lot of the problems are similar.
Within our department we have people who do clinical interventions, who do cognitive neuroscience, and people like me who do basic neuroscience all collaborating around autism spectrum disorders, for instance. When there’s a clinical thing like that, where you have a biological element that’s apparent and you have a cognitive and clinical aspects, you see a lot of overlap and interdisciplinary talk within departments. But, the further you get from that kind of stuff, it seems like there’s less interaction.
I actually discovered your article because I was searching for information on SNPs, single nucleotide polymorphisms. How do those fit into the research that you do? My understanding of SNPs — or “snips” — is pretty much nonexistent that they are a sort of fingerprint, I guess, within the DNA … ? Yeah. So maybe you can clear that up for me. [Laugh]
Sure. Yeah, so SNPs are just fine-scale mutations. That’s literally what they are: they’re mutations in a single nucleotide of a gene. Part of how the whole Human Genome Project was sold to the public was, “We are going to discover the causes for all of these genes because they all live in the blueprint of our genome in our DNA.”
And that kind of “gene hypothesis” causation for complex diseases has dominated a lot of research over the past 20 or so years — in complex diseases including mental disorders — and so people have been doing genome-wide associational studies [or GWAS], looking for SNPs that are associated with diseases, for a long time.
I have some issues with it. I think it’s useful, but if you think from an evolutionary-biological perspective, things that are major contributors to disease that are genes are removed from populations. They don’t survive. That’s how natural selection works.
And so the probability is — if you take account of evolution — that major contributors to disease, major genetic contributors to disease, are unlikely to exist in other than small portions of the population. They’re likely to be rare and, in fact, that’s what all the data shows thus far. The GWAS, for instance, that we just had for schizophrenia in the past year showed that something like 120-odd polymorphisms — so that’s SNPs — contribute less than seven percent of the risk for schizophrenia. They had over 100,000 subjects in that study.
I think the answer’s much more likely to lie less in this hypothesis that you have “bad genes” or you’re just not getting enough serotonin, but in the fact that you’re having a complex response to a difficult social environment.
So these are huge studies that are very expensive and I don’t doubt their value, but on the other hand I am personally somewhat dubious of the gene hypothesis of complex mental disorders. Other than, like, you have a brain and it’s human.
I think it’s much more complicated than that. I mean, I think in something like depression — we see that, or something like it, in other species. That’s what Sapolsky started with: the fact that a lot of his low-dominance animals [whom he studied] looked depressed, they looked sick. There was an interrelation between these things, and if we think about depression, I think the answer’s much more likely to lie less in this hypothesis that you have “bad genes” or you’re just not getting enough serotonin, but in the fact that you’re having a complex response to a difficult social environment.
Maybe you’ve been beaten as a kid, and so you’ve been left with a legacy of perception of other people that’s fundamentally based on hostility. You’re expecting the beating because that’s what your parents modeled for you. And that’s not your gene’s problem, right? [Laugh]
That’s your parents’ problem.
Yes. That’s where the epigenetics come in!
Right? Or maybe you’re depressed because you’re — yeah. I make this point at conferences and in talks. Maybe you’re depressed because you have a crappy job or you have a crappy husband, and maybe you need a divorce.
I mean, it’s true! The whole psychopharmacological, the excessively biological approach — and I say this as someone who’s really biological in my approach to mental illness — is that it has let us step away from the fact that people have real problems in their lives, and that those problems are problems. [Laugh] Maybe Prozac is not the solution to your marriage, or Prozac is not a solution for your abusive childhood.
It’s palliative, it’s something that helps you cope with it, but it’s not the same as doing therapy and really talking through and dealing with the fact that you have habits of mind and habits of behavior that you acquired from some very pathological parents and that you need to process out of that.
So, in terms of SNPs, I think that they’re scientifically important, but I tend to think that genetic explanations for mental illness are oversold, and that we really do need to step back and think, “What is this really? Let’s go back and look at the patients. Let’s go back and look at their life histories.” Because we do have very powerful — I mean, I think you might have quoted Felitti — the fact that your suicide risk goes up 3,000 percent or whatever, just from having a bad childhood.
That’s not your genes!
You know? That’s your environment. But it’s obviously something that lasts and sticks with you. And so, to the extent that we believe that our mind resides in the biological entity — which is our brain — I think there has to be something happening there, but I don’t believe it’s … it’s not an SNP, and it’s probably not as simple as one neurochemical being out of whack, either. I think it’s much more complicated.
And honestly I don’t think we should be surprised by that [idea]. The brain is the most complicated artifact humans have ever come across, and it remains really complicated. [Laugh] It should be fairly unsurprising!
But, as scientists, we are human. Our brains are limited. We’d like to think that we’ve got this simple, totalizing idea that explains everything. And it’s hard — and it’s easier to sell those ideas, because everybody likes those ideas. It’s like those viral marketing things on the Internet: one weird trick to get rid of belly fat or whatever it is that —
— you know?
That works because that one simple thing will explain blah blah blah, and that works in the marketing of scientific ideas as much as it does in spam. [Laugh]
[Laugh] Yeah. Before his fall from grace, Jonah Lehrer — who kind of wrote pop neuroscience articles — [Laugh]
— there was an article asking, “What is the function of depression?” In one portion of that essay, Lehrer was quoting a psychiatrist who said, “I gave this woman medication, and she was happier, and then I asked her, ‘How are things going?’ The woman said, ‘Well, I’m no longer suicidal, but I’m still married to the same asshole.’” [Laugh]
In recent years, Thomson has cut back on antidepressant prescriptions, because, he says, he now believes that the drugs can sometimes interfere with genuine recovery, making it harder for people to resolve their social dilemmas. “I remember one patient who came in and said she needed to reduce her dosage,” he says. “I asked her if the antidepressants were working, and she said something I’ll never forget. ‘Yes, they’re working great,’ she told me. ‘I feel so much better. But I’m still married to the same alcoholic son of a bitch. It’s just now he’s tolerable.’ ”
—Jonah Lehrer, “Depression’s Upside”; The New York Times (2010)
— and I think what you’re alluding to is sort of what I was asking about earlier. I call it the qualitative factors in people’s lives, the environment, where people are — there are these structural things like microaggressions, if you’re a person of color, if you’re a young gay child — all of these different factors that —
— as a uniquely, highly social species, we’re particularly vulnerable to social rejection. And so, in your — this article that I purchased off of ScienceDirect! — you talk about chronic social defeat. Could you talk about that a little bit?
Yeah. So that was a model that was developed a while ago in Siberian hamsters [Huhman, 2006] — and it’s been made popular by Eric Nestler, who’s Chief of Neuroscience at Mount Sinai [Hospital] in New York.
What it is, basically, is it’s doing something that’s ethologically relevant — it’s [chronic social defeat] something that actually happens in rats and mice, and that is that a dominant male — typically — will beat up on non-dominant males. And this is a part of how dominance hierarchies are enforced is that there is – in mice, at least — a certain level of physical aggression, and so you basically build that so that the animals aren’t killed, because mice are not very nice to one another. They will kill each other if you give them a chance.
You basically give them 10-minute exposures over the course of 10 days, where the animal can’t physically aggress against the other: you leave them [the non-dominant mouse] under a dome in the cage so that they can smell the aggressive mouse, but [that dominant mouse] can’t hurt it. You do that for 10 days and the animal, unsurprisingly perhaps, starts to show a depressive-like phenotype — they respond to a lot of these basic assays of depressive behavior like a depressed person would, or at least [how] we’d likely think they would. And it’s something [where] you can rescue some of those effects by giving tricyclic antidepressants.
So it has a lot of both “face” validity and ethological validity and it’s, I think, a much better way of modeling these things in rodents, to the extent that these things are model-able in rodents. I think this is probably the best way available right now to do it, because it’s plugging into something that actually happens to rodents, and it fits with what we know about depression in humans — that depression in humans is often a disorder of social distress or social subordination.
Or social isolation. Social isolation is another model that probably needs more study, but not in mice because [male] mice actually get happier when they’re socially isolated.
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