Neuron Culture

Muddy Ground

The term depression is so messy, muddy, and imprecise that almost any talk about the nature of depression will encounter sloppy ground. Atop that, psychiatry itself is similarly messy and confused.

By chance and rich luck, Louis Menand published a fine article pointing out this muck and confusion the same week that Lehrer's piece appeared. Menand opens by describing a hypothetical case of "situational depression" (You've been laid off and are feeling bleak and increasingly withdrawn...), then asking you to consider whether you should follow your doctor's suggestion that you start a course of antidepressants. That's just the setup, of course, for a knockdown:

However you go about making this decision [i.e., whether to take the meds], do not read the psychiatric literature. Everything in it, from the science (do the meds really work?) to the metaphysics (is depression really a disease?), will confuse you. There is little agreement about what causes depression and no consensus about what cures it. Virtually no scientist subscribes to the man-in-the-waiting-room theory, which is that depression is caused by a lack of serotonin, but many people report that they feel better when they take drugs that affect serotonin and other brain chemicals.

Is depression--insomnia, irritability, lack of energy, loss of libido, and so on--like a fever or like a disease? Do patients complain of these symptoms because they have contracted the neurological equivalent of an infection? Or do the accompanying mental states (thoughts that my existence is pointless, nobody loves me, etc.) have real meaning? If people feel depressed because they have a disease in their brains, then there is no reason to pay much attention to their tales of woe, and medication is the most sensible way to cure them. Peter Kramer, in "Against Depression" (2005), describes a patient who, after she recovered from depression, accused him of taking what she had said in therapy too seriously. It was the depression talking, she told him, not her.

This provides valuable context for considering the ART model. The history Menand covers reminds us that psychiatry and its terminology are sloppy — and that you court difficulty and danger when you discuss science (perhaps especially the science of the mind) without some historical perspective. Every time you zoom out your view of psychiatry and its diagnostic categories, for instance, you see terrain stretching at a scale and in corrugations that the previous, more tightly framed perspective never suggested.

This applies especially to "depression" — a term I air-quote because it's enormously imprecise abouit not just degree and duration of symptoms -- that is, whether you're sad for a few days or in couchbound despair for years -- but also about the biological and neural dynamics involved.

Lehrer notes, for instance, that some studies show that depression generates increased activity in the ruminative, problem-solving areas of the prefrontal cortex, or PFC. Ries counters that other studies show a decrease in PFC activity. Indeed, researchers have found both things.

They've found similar 180-degree differences in how recovery from depression affects PFC activity. A few years back, Emory neurologist Helen Mayberg and colleagues looked at the neural activity of depressed patients as they responded successfully to treatment — drugs in some cases, cognitive behavioral therapy in others. In both cases, PFC activity changed. But it ramped up in people who got better while on medication, and down in people who get better while undergoing cognitive behavioral therapy or CBT. (I discussed this study and its implications in a profile of Mayberg I wrote a while back. My Times Magazine article on Mayberg's experimental brain surgery trial also sheds some light on depression's nature.)

How so? It took a while for Mayberg to figure it out:

“Oh man,” says Mayberg. “I was stumped. For a while I had to just set it aside.” Why did the CBT patients’ frontal activity go from high to low as they got better, rather than vice-versa?

She finally realized that the successful CBT patients were almost by definition going to show this pattern. In CBT, patients learn to recognize and change thought patterns that help depress them. An active frontal area, then, was virtually required to make CBT work. The patients who responded to CBT did so either because they were busier thinkers by nature (and therefore more amenable to CBT) or were, when scanned at the beginning of the study, in an earlier stage of depression in which their frontal areas could still rise to the task. The CBT responders entered the study already trying to think their way out of their depression. The scans showing these initial high levels of frontal activity, then, “were pictures,” as Mayberg put it, “of the tug-of-war between the depression and their attempt to self-correct.” When their attempt succeeded, the frontal areas could relax, and the scans showed the reduced activity.

This is a major point: It's not just depression that varies tremendously; people's reactions to it, and their possible paths out of it (and, doubtless, into it), also vary tremendously. This adds to the difficulty of offering any sweeping statements or theories about depression's nature. Yet sometimes we need sweeping statements to force a broader view.

Back to ART

Which returns us to the analytic-ruminative model. As I noted, I think the ART model has limits. Yet unlike some of Jonah's critics, I think (and I regret to report that I speak from experience as well as study) that even nasty, long, potentially lethal depressive episodes can (but don't always) inspire crucial insight. Why would some episodes do so and others not? Well, the factors I can suggest include a) the nature of the depression (particularly whether it's due to situations you have the power to change) and b) whether you possess at the time the combination of cognitive chops, inclination, and social and/or professional support to generate some insight. In other words, if you're down, maybe even really down, because a particular situation is defeating you, and ... (here you can add a bunch of ifs having to do with your willingness and ability to work the problem, the quality of your therapist, the people around you, etc.) ... then you might solve a key problem or gain a key insight.

The insight might even turn an unsatisfying life into one deeply rewarding. A psychiatrist once told m, and I think he's right about this, that most people don't face a whole bunch of different problems during their lives; instead, you tend to face the same problem presenting itself in different forms. Learn to recognize and better handle the core problem (which you are always, of course, part of), and you'll cut a smoother path. And this recognition can happen even amidst of intense depression; in fact, the depression may the only thing capable of driving you to do the needed work.

In this sense, the ART model offers a crucial truth. Yet it's part of the muddle of this thing that many depressions — perhaps most but not all deadly serious depressions — destroy rather than create. Thus the depressed PFC activity; thus the anemic powers of thought, memory, and will; thus the frozen emotions, the seized cognitive powers, the sense that every road is fogged over. These depressions just smother you.

Despite all the complexity, it's that simple: Sometimes, for some people, depression ramps up constructive thinking; for other people (or at other times for the same people for whom depression sometimes brings insight), it smothers it. Did Virginia Woolf's bipolar depression bring her insight and creativity? Quite possibly. Yet in the end it drowned her.

The Orchid Angle

The question of depression generating insight leads inevitably to the much-discussed (and sometimes disputed) association between depression and creativity. Does depression, either unipolar or bipolar, generate creativity? There's some evidence it does. There are links. But what's the source of the link?

Well, depression might, as above, sometimes directly inspires introspection and insights contributing to creativity. That's a direct causal relation.

But I think that some attributing creativity to depression may, in some cases and perhaps in general, mistake association for cause — that depression is not the thing that generates creativity and insight but a byproduct of another trait that does. And that this other trait is sensitivity — and particularly the sensitivity that comes from the "sensitivity" genes I recently wrote about in the Atlantic.

The sensitivity hypothesis asserts that some gene variants presently considered "risk genes" for mental health problems in people with stressful lives are actually "sensitivity genes" that make you more sensitive to all experience. One of the genes in question is the serotonin transporter gene, or SERT gene, which helps regulate the neurotransmitter serotonin. Two of the three variants of this gene (the "short-short" or s/s version and the "short-long" or s/l versions) have been shown to put people with stressful life histories at greater risk for depression. The sensitivity or orchid hypothesis asserts that these short SERT variants don't make people more sensitive to bad experience but to all experience, bad or good. It's not a "depression gene" but a sensitivity gene. What you make of that sensitivity naturally depends on other assets or experiences you have.

If this is so, then it's possible that this sensitivity hypothesis may account (wholly or in part) for findings that "depressed people" have more insights or creativity -- only it's not necessarily the depression that generates the insight, it's the heightened sensitivity.

This comes close to being the sort of "spandrel" that Ron Pies discusses in his critique of Lehrer's article. As Pies explains, a spandel, in evo talk, is a neutral or disadvantageous trait that comes along as a byproduct (or one expression) of some larger, broader trait that is adaptive:

In architecture, a spandrel is simply the space between two arches. Molecular evolutionist Richard Lewontin and paleontologist Steven Jay Gould argued that many traits in nature are nonadaptive, and--like spandrels--are simply byproducts of other, presumably adaptive traits. For example, Gould notes that bones are made of calcite and apatite for adaptive reasons, but they are white simply because that's the color dictated by those minerals--not because "whiteness" confers an adaptive advantage.

In her upcoming book, The Pocket Therapist, Therese J. Borchard candidly observes that, "...the sensitivity that produces so much of my [emotional] pain is precisely what makes me the compassionate person I am." ... I believe that Borchard may be gesturing toward one possible mechanism by which depression is genetically conserved: not by virtue of its adaptive value, but by virtue of depression's ability to "hitchhike" along -- as a spandrel -- with a sensitive, altruistic, and compassionate nature: traits that are indeed adaptive, in many social contexts.

As Borchard wisely counsels, we should not renounce or disown the part of us that produces depression -- it is a piece of our messy, complex, and wondrous humanity. And, to be sure: ordinary sadness or grief may indeed be a good teacher. We should not rush to suppress or "medicate" what Thomas à Kempis called "the proper sorrows of the soul." At the same time, we should be under no illusion that severe clinical depression is a "clarifying force" that helps us navigate life's complex problems. That, in my view, is a well-intentioned but destructive myth.

I differ with Pies here. I think — I think I know — that severe clinical depression can sometimes, in some cases, serve as "'a clarifying force' that helps us navigate life's complex problems." At other times, in other cases and other people, serious depression is indeed but a dangerous byproduct — a spandrel —that comes from a heightened sensitivity. And that sensitivity may rise, as described in my article, from gene variants such as the S/S and S/L SERT alleles.

Doubtless the tremendous variability in depression, and the wiggy variations in its association with insight, creativity, and other upsides, depends too on other variables about which we're clueless. Much murk remains

So does this get us anywhere? I think so. Some of Lehrer's critics said he'd contributed but a "sloppy and insensitive article" that insulted the depressed and did the discussion harm. I say otherwise. Given depression's immense complexity, not to mention the muddle that is psychiatry, I think we will always, as Menand put it, "lurch" about rather clumsily in our attempts to understand it.Yet even when people articulate fairly stark positions, as Jonah did in his article and Pies in his critiques (actually, because they take stark positions), these dust-ups can, if people engage them with a willingness to look deeper, think a bit, modify their positions, perhaps even ruminate a bit, produce some useful insights. The muddle can produce clarity, the noise an upside.