The Frontal Cortex


First of all, thank you to everyone who took the time to write and comment on my recent article on depression. I really appreciated all the insightful emails and I’m trying to respond to every one. In the meantime, I wanted to address some important criticisms of the analytic-rumination hypothesis and of my article, which were raised by an academic psychiatrist. I’ve reproduced his criticisms, and my replies, below:

First, you write “depression is everywhere, as inescapable as the common cold”. No, this is flatly wrong. Major depression is estimated by an absurdly broad range of epidemiological studies to have a slightly less than 20% lifetime prevalence.

I talked to more than a dozen mental health professionals about this precise issue. The general consensus, as near as I could tell, was that the 20 percent range is actually at the low end of the current estimates for lifetime prevalence for MDD. One of the problems with estimating “lifetime prevalence” is that most surveys are based on retrospective memories, as people try to reconstruct their state of mind decades earlier. There’s good evidence that such surveys reliably underestimate the number of people who suffer from major depressive disorder. Consider this recent study, which conducted interviews with a random sample of Canadians during a relatively brief time span. Here are their conclusions:

The annual prevalence of MDD ranged between 4% and 5% of the population during each assessment, consistent with existing literature. However, 19.7% of the population had at least one major depressive episode during follow-up. This included 24.2% of women and 14.2% of men. These estimates are nearly twice as high as the lifetime prevalence of major depressive episodes reported by cross-sectional studies during same time interval. CONCLUSION: In this study, prospectively observed cumulative prevalence over a relatively brief interval of time exceeded lifetime prevalence estimates by a considerable extent. This supports the idea that lifetime prevalence estimates are vulnerable to recall bias and that existing estimates are too low for this reason.

And this is merely the latest longitudinal study to estimate a significantly higher percentage of people suffering from major depressive disorder. One longitudinal study of adolescents living in New Zealand showed that 37% satisfied either the third edition-revised of the DSM or the DSM-IV-TR for a diagnosis of a lifetime episode of major depression.

Obviously, it will always be difficult to precisely estimate the percentage of people suffering from a condition over a long period of time. For one thing, the diagnosis of major depressive disorder is itself in flux. However, I think there are good reasons to believe that the standard estimate of 20 percent is at the low end of the spectrum, especially given current trends. Since 1980, the diagnosis of depression has been rapidly increasing across every segment of the population. To take but one example: between 1992 and 1998 there was a 107 percent increase in depression among the elderly.

Here’s another criticism:

Next – and this is most surprising to me – you rehash their arguments about the VLPFC as though it exists as a kind of anatomic source of depression. Surely you are aware – in fact I know you are because you have written at other times about this very topic – about just how complicated our current evidence base is in the area of depression. I mean even just to mention the well known deficits in hippocampal neurogenesis, the excess activity of the amygdala, or any number of other known reciprocal interactions between subcortical and prefrontal cortices would help an educated lay reader understand that while the VLPFC may be particularly active in ruminative processes, it still needs to be understood in the context of broader functional neuroanatomic findings in depression.

I’m sympathetic to this criticism. In an ideal world, I would have spent another thousand words or so outlining the neuroscience of depression; there is always more to say about a subject as rich and complex as mental illness. As noted above, there are many changes visible in the brains of people suffering from major depressive disorder. (I’ve written at length in other publications about many of these changes, particularly the reduction of neurogenesis.) It’s also worth pointing out that many of these changes don’t appear to be unique to major depressive disorder, but are rather part of larger response to chronic stress. As we now know, chronic stress is toxic for the brain, and tends to shrink the hippocampus and swell the amygdala. (Of course, like just about result in neuro-psychiatry, this claim remains controversial.) Alas, this was not an article about the neuroscience of depression, and so I was only able to discuss the proposed neural substrate of rumination in the VLPFC as it pertained to the analytic-rumination hypothesis. I never claim, of course, that the VLPC is the neural signature for MDD.

I’ve also received several emails from psychiatrists who criticize my reference to the DSM. Here’s a sample email:

I’ve begun e-mailing every author I encounter who uses a phrase like “diagnostic bible” to describe the DSM to ask them to please think a little further on the subject. If there is any use for the DSM at all in the real world, it arises from the intention to create a heuristic document. That is, the very purpose of DSM is to closely describe our current understanding of diagnostic entities so that they may be tested against reality. The purpose is not to hand down scripture from psychiatric gods to psychiatric priests; the purpose is to provide a little handbook that a large group of explorers can use to map out a territory. In psychiatry, we are still trying to figure out whether this or that psychiatric diagnosis accurately describes anything in the real world, or whether it is simply a projection of the the mind of an individual or a culture. DSM, at its best, recognizes that we are largely still groping in the dark, trying to discern what is illness and what is health, whether treatment is needed or can be accomplished.

I think this is right, and I regret my use of the phrase “bible of psychiatry”. I had no intention of suggesting that the DSM is a document of faith, only that it’s an authoritative resource for modern psychiatry. But it was a thoughtless, cliched description.

Needless to say, there are many more criticisms to make, both of the ideas described in the article and of the article itself. As you can imagine, this is a difficult subject to write about, in large part because the facts themselves are so contested. As demonstrated in this widely cited survey, patients with major depressive disorder exist on a continuum of severity, from mild to severe, making it ridiculous to suggest that there is, or should be, only one form of treatment. If a treatment works for the individual patient that is the only fact that matters. Everything else is mere theory.


  1. #1 ChadCroft
    March 1, 2010

    I enjoyed reading your comments and believe that the DSM is a conundrum. One of the main reasons is that it is a process of labeling interactive elements of the human/social landscape and that very process alters the landscape itself. It is somewhat like Escher’s drawing of a hand drawing itself. It almost seems that with each new edition of the DSM it becomes more clear that it has outlived its usefulness as a diagnostic tool. It also seems that any process of labeling is doomed to failure because such process is by definition intended for the purposes of the professional and not for the subject.

  2. #2 becca
    March 1, 2010

    “One of the problems with estimating “lifetime prevalence” is that most surveys are based on retrospective memories, as people try to reconstruct their state of mind decades earlier. There’s good evidence that such surveys reliably underestimate the number of people who suffer from major depressive disorder.”
    Is this true of other conditions? Does it suggest anything about the likelihood depression is adaptive with respect to learning from bad situations?

  3. #3 royniles
    March 1, 2010

    Depression is, or results from, a defense mechanism, and all such mechanisms are meant to have an upside if and when they work. Pointing that out as the upside would seem to have been sufficient as a premise for the article, but not for the silver lined conclusion .
    Not pointing out that these mechanisms need to evolve their defenses was the problem. because there is no upside in the fact that these defenses often go awry, and leave us with no defense at all for both the near and far futures.
    Which you still haven’t gotten around to doing..

  4. #4 C H Paquette
    March 1, 2010

    Bravo Jonah! I’ve read your NYT piece twice now, as well as the New Yorker article ‘Head Case’ by Louis Menand. (It is very interesting that both were published the same week). I don’t agree with most of the analytic-rumination hypothesis, but commend you for tackling this subject and following up on all of the emails and critiques. It’s what makes this blog so enjoyable to follow.

  5. #5 Cole Bitting
    March 1, 2010

    I read the NYTimes article as a discussion on the general topic of depression rather than one related specifically to clinical depression or MDD. No wonder the pot was stirred so well.

    I think you are having a Steven Pinker moment. Some people refuse, on general principal, the question: does depression have upside?

    One issue which could be explored. The behavior of depression can be adaptive and provide upside even if the extended memory of the feeling of depression can be such a ravaging experience.

    This whole discussion also also goes in the direction of posttraumatic growth, and there again, some don’t want to recognize the possibility that trauma might have upside. [This topic is one I write on a lot.]

  6. #6 Michelle
    March 1, 2010

    This comment has no relevance to science. I am a layman with very limited knowledge of neuroscience and psychology, but I enjoy reading your blog and book. I just wanted to tell you that I appreciate your active responses to comments and criticism. Thank you.

    “He had spent seven years of his life with Tereza, and now he realised that those years were more attractive in retrospect than they were when he was living them.” Also, I’ve been on a Milan Kundera kick lately; I’m currently working through The Unbearable Lightness of Being. I just read this sentence, which refers more to love and philosophy than to depression, but out of context it reminded me of your discussion about retrospective surveying of depression from today’s post. Again, thank you.

  7. #7 Amanda Wang
    March 1, 2010

    I just wanted to congratulate you on being the number one most emailed article on the NYT today! I’ve read both of your books and am enamored with the way you interweave art, literature and science together (especially Keats!). It’s too bad that science and art is often looked at in silos and are not as integrated into our American psyche.

    It takes great courage to be open to criticism and I believe —— with only personal experience to back it up —— that what matters to most people who have a debilitating illness is that they have a purpose to reach for. And if that means that there’s even an inkling of a chance that the struggles and pain we are going through has an upside, then I’m all for it.

    You’ve given a new voice to those who often hear only the negative things about mental illnesses that they have. Thanks!

  8. #8 Dinah
    March 1, 2010

    I put my comments in a post on Shrink Rap. Feel free to visit.

  9. #9 Ronald Pies MD
    March 1, 2010

    from Ronald Pies MD

    Readers of this blog may be interested in my rejoinder to Mr. Lehrer’s NY Times piece, at:

    Although I am very critical of Mr. Lehrer’s essay, I want to make it clear that I bear him no animus, and that I consider him a thoughtful, intelligent, and creative writer. Had I been a senior editor at the NY Times Magazine, I would have said to Mr. Lehrer, “Why don’t you talk to two or three directors of mood disorder clinics, to get their take, and do a more thorough review of that prefrontal cortex literature. Oh, and–why not talk to a couple of people who have actually been through a severe depressive bout, or read some accounts by them in the published literature?”

    As a writer and blogger myself, I am sympathetic to the limitations of time and space that constrain what any writer can do. My critique is thus more in sorrow than in anger, and I hope Mr. Lehrer will take it in that spirit.

    Having tried to help seriously depressed individuals for nearly 30 years–and seen the destruction major depression can wreak on both patients and families–I confess to a certain irritation and dismay when I read about half-baked theories claiming that major depression is “adaptive”. The 15% mortality rate in this condition (based on naturalistic studies), mainly due to suicide, speaks volumes about how
    “adaptive” depression is.

    Finally, in my own essay, I offer a tentative hypothesis regarding depression as a “spandrel”–i.e., as a non-adaptive trait that is a kind of genetic “hitch-hiker”, on the backs of more adaptive traits. I want to acknowledge, as I just discovered today, that my colleague, Dr. Peter Kramer, also suggested this possibility in his excellent book, “Against Depression”. Further discussion of this issue can also be found on the website of Prof. Jerry Coyne PhD [].


    Ronald Pies MD
    Tufts USM and
    Upstate Medical University

  10. #10 Marian
    March 1, 2010

    I very much enjoyed your article. Indeed, Andrews and Thomson’s observations resonate to a great extent with my own experience – not of “depression”, but of “psychosis”. So, the next question, which some people like psychologist Al Galves already have made quite successful attempts to answer, is if there maybe is an evolutionary purpose to “psychosis” as well.

    In my opinion, there’s absolutely no need for you to regret your use of the phrase “bible of psychiatry”.

    While the critical comment you quote states how the DSM maybe should be perceived and applied – a little (???) handbook to help map out a territory – this definitely isn’t how it usually is perceived and applied in practice, which is, in fact, as the one and only truth, a bible. Anyhow, one might argue that the resemblance to a certain book, originally published as early as 1487, is even more striking…

    Maybe, because “map out a territory” reminds me of what Joanne Greenberg says in Daniel Mackler’s film Take These Broken Wings about her having the map, and Frieda Fromm-Reichmann doing nothing but holding the light. To me the DSM looks like the wannabe-explorers attempt to erase the map of experience in favor of their own fictional one.

  11. #11 CM
    March 1, 2010

    “If a treatment works for the individual patient that is the only fact that matters. Everything else is mere theory.” Really? How are we meant to work this out, in the individual, n=1, case. This is the sort of flaccid thinking that lets homeopaths get away (occasionally literally) with murder.

    Time to remove ‘science’ from the ‘scienceblogs’ url. Please update your blogrolls to

  12. #12 Dr. Meh
    March 1, 2010

    Your “article” is a mindless, disgusting, self-masturbatory journey into a hypothetical state of consciousness fully removed from the actuality of psychiatric care. In other words, you have some quasi-romantic vision of mental illness as a creative and intellectual pursuit rather than as a legitimate disorder of neurotransmitter and receptor.

    Only someone whose primary profession had never ventured into the care of an actual patient with actual suicidality could argue that depression writ large is beneficial. Certainly, among the worried well and the mildly depressed, inertia and thoughtfulness can provide a modest benefit. So, what about the rest of us, whose lives have been hampered and hindered by tricks of our neurochemistry? Where is the benefit provided by crippling mental illness? You make no distinction, ergo there must be one.

    I’ll wait while you figure some hand-waving explanation about how we can’t treat the extremes as if they were representative of the middle.

    I, too, am a PhD in neuroscience. I am not so accomplished as you, however. No, I’ve had to fight to get out of bed most days, try to locate enough motivation in my starving frontal lobes to move around and do my work. Flicker my attention back and forth between those terrible thoughts and the task at hand. And this with the best that psychology and psychiatry have to offer! You, of course, would say that this is all for a good cause. Pray tell, what would that be? Oh right, an intellectual exercise. Just like Sylvia Plath’s intellectual exercises and wonderful writing…right before she offed herself with an appliance.

    You are young. Perhaps you will breed. You will likely breed smart children…most of whom, in my experience, have bouts of serious depression. When you see the agony on your child’s face or that of any other human (real, not theoretical), you might question the adaptive purpose. Then again, maybe not.

  13. #13 Charles V. Packer
    March 2, 2010

    The evolutionary roots of depression might be established
    more soundly if it could be shown that it was similar,
    neurophysiologically, to some simpler, more obviously
    adaptive behavior. We had a cat that at a young age lost
    its naivete about dogs traumatically, by being attacked
    by one. It went into a profound funk for several days —
    a kind of trance. Such a reaction was a surprise to me
    because its injuries consisted of just a few bite marks.
    It occurred to me that it would be advantageous for an
    animal to hunker down and hide until its injuries healed.
    Could our cat have been ruminating, too?

  14. #14 Pepper
    March 2, 2010

    Dr. Meh, I’ve been equally depressed as you and I agree with Jonah.

    I’m sorry people can’t accept that others experience, even if not the same (in terms of how it is interpreted) can be valid.

    I won’t step on your experience of your reality. Please accept that some of us see value in the pain life has dealt us.

    By the way, I don’t have a PhD…

  15. #15 daniel k
    March 2, 2010

    ” … yeah my wife was ***ed and my daughter was ***ed, and now there’s this guy telling me that there is an upside …”

  16. #16 stop spam
    March 2, 2010

    Jonah you hire forum spammers to get people to notice you? Cause it sure looks that way.

  17. #17 Tom Michael
    March 3, 2010

    @Pepper & Dr Meh – I’m also a PhD student who has suffered from depression. On thing we need to remember is that even if we have suffered from depression, we can’t say for sure that our experience was as bad as someone elses. Sure, our behaviour may have been similar, but until the invention of some kind of consciousness sharing telepathy machine, we can’t be sure that our conscious experience was the same.

    I’m leaning towards Dr Pies description of depression as a spandrel – It might be adaptive for a small subset of problems, but on the whole it is a very maladaptive illness. Someone else mentioned the positive feedback loop of being depressed about being depressed. Such a feedback loop describes the ruminations common in depression – it could be that the interaction between our more primitive emotional areas (hippocampus & amygdalae) and our more human evolved conscious control areas (prefrontal cortex) mean that humans are susceptible to rumination far more than animals. Charles Packer above desribes his cat as being depressed, but only for a few days.

    If humans only got depressed for a few days, that would be better than months/years long illness. But because we can ruminate, and get depressed about being depressed, this forms a very very maladaptive feedback loop.

    It could be that earlier in our evolution, depression was useful, but that now we are intelligent thinkers, a Spandrel has evolved which is maladaptive. However, it is likely to stay because both negative emotion and intelligence are vital to our survival. Its an awful twist of fate that the combination of the two can result in such awful suffering.

    (My background – have had several episodes of depression, typically lasting up to 6 months. Currently OK – trying to get PhD in neuropsychology)

  18. #18 Thos. Cochrane
    March 3, 2010

    In your defense, Jonah…

    Even if the prevalence of depression is 20% (or even lower), you wouldn’t be crazy to describe depression as being “everywhere.” If 1 out of every 5 people you meet has depression, it’s pretty much “everywhere.”

    Related: Anyone know what the prevalence (not incidence, prevalence) of the common cold is? It’s gotta be a LOT less than 20%.

  19. #19 Marian
    March 3, 2010

    @Tom Michael: If I read your reply to Pepper and Dr Meh right – and please correct me if I don’t! – you assume that, maybe, Pepper hasn’t suffered quite as much as Dr Meh, why s/he managed to turn the experience into something positive, while Dr Meh didn’t. On what basis do you make such an assumption? Do you know both of them personally?

  20. #20 Ronald Pies MD
    March 3, 2010

    Very interesting comments, everyone!

    So much of the debate turns on what is meant by the term “depression”. A major problem with Jonah Lehrer’s original piece is that he did not fully clarify what he meant by “depression” –though it is quite clear that the paper on which Lehrer bases his evolutionary claims used the term “depression” to describe DSM-IV “major depression”.
    Second, we need to distinguish three related yet separate concepts and claims: (1) major depression is “instructive”; (2) major depression is “adaptive”; and (3) major depression is “conducive to significant mental health (or physical health) benefits.”
    I would not deny that depression, like other challenges in life, may be “instructive” for some proportion of individuals–though probably a minority. I have very serious doubts (as do most of my colleagues) that major depression is “adaptive” in any significant way, though perhaps very brief and mild bouts of depression could confer some modest advantages in an evolutionary sense; e.g., by increasing one’s empathy toward others, which could be highly adaptive in obvious ways. [cf. “A broken heart prepares man for the service of God, but dejection corrodes service.”— Rabbi Bunam of Pzysha].
    This could be true, in theory, for more severe depression, but there, the maladaptive aspects of the illness would likely outweigh any modest advantages by a huge margin; e.g., the 15% mortality rate in major depression (naturalistic studies), mostly by suicide.
    As regards mental health benefits, such as increased clarity of thought or problem-solving ability issuing from depression, this strikes me as, well–unlikely in the extreme (to use civil language!). So, too, with any putative physical benefits–on the contrary, major depression is associated with substantially increased health risks, such as cardiovascular disease and diabetes.
    I also think it’s helpful to ask, in philosopher William James’s terms: what is the “cash value” of the idea that major depression confers an adaptive advantage by improving our problem-solving skills? Let’s stipulate such an advantage. So what? Where does that information get us, in our attempt to help people live better, more productive lives? How does it help our severely depressed patients? Should we encourage patients to prolong their depressive bouts in order to increase their analytic abilities?
    We have known for decades that the sickle-cell trait provides a survival advantage over people with normal hemoglobin in regions where malaria is endemic—but this trait also increases rates of painful and debilitating sickle-cell disease. If, in a malaria-rich environment, we had the means both to reverse the sickle cell trait and to prevent malaria, would we not do so? By analogy: if we could prevent major depression with all its disadvantages, but still find ways to improve people’s “problem-solving skills”, would we not do so? Surely there are ways of teaching people how to “analyze” their problems without asking them to bear the immense burdens of major depression! By the way: William Styron’s severe depression may have been related in part to alcohol and/or prescription drug misuse—but the horrible symptoms he describes are not at all atypical in many, many severely depressed patients.
    None of this is to say that people who are depressed are in any way “broken” and must be “fixed”. One should never confuse a person’s mood state or illness with his or her value or goodness as a human being!
    The Talmud teaches us that we should learn from all persons, even a thief. For example, thieves work hard at night! I see major depression as a kind of thief. Now, being robbed (of happiness, pleasure, ease of mind and body, etc.) may indeed be instructive–one learns courage, resilience, caution, and the need to take care of oneself. But a thief is still a thief–and few of us would recommend a “good burglary” to our friends or family, as a means of instruction in life’s lessons!
    Ronald Pies MD

  21. #21 Marian
    March 4, 2010

    @Ronald Pies: Who said, we should prolongue bouts of “major depression”? I didn’t read that anywhere in the article. On the contrary, doesn’t it say in the article that we simply should value the enhanced skills for problem-solving which come along with “depression”, and, instead of ignoring, respectively suppressing these skills by treating them, too, as undesirable symptoms, should make constructive use of them in treatment, so that the problem(s) eventually can be solved, instead of merely ignored, respectively suppressed?

    My experience is that it is the latter, not the former, which prolongues suffering. As long as the problem isn’t solved, it will come bouncing back time and again, and we end up with “chronic mental illness”, “depression” or other.

    Andrews and Thomson’s approach seems to be a lot more focussed on potentially health and well-being enhancing qualities of the state of mind that is called “depression”, than the usual approach that doesn’t see anything else but pathology. To me it is obvious which approach is the most constructive in the long run.

  22. #22 Rossa Forbes MBA
    March 4, 2010

    I’m no PhD, nor am I depressed, but here are my two cents worth in response to Dr. Pie’s article at Psychcentral. What does it cost to anyone to point out that depression has an upside? Some people will grab this lifeline. Schizophrenia, with which I am familiar, has many upsides, so depression could and should have some as well, for those people at least who want to take responsbility for their health into their own hands, rather than blame faulty neurotransmitters. You can see it here in the comments. There are the glass half full and the glass half empty people. Rationales for behavior based on brain biochemistry lead to loss of personal responsbility for your own health. Some people are not depressed by this thought.

  23. #23 Ronald Pies MD
    March 4, 2010

    The problem with giving all this press to the supposed “upside” of depression is that it can discourage seriously ill people from seeking help; and instead, encourage them to “buck up”, “pull themselves up by their bootstraps”, “wait it out”, and other such Calvinist nonsense, in order to reap the “benefits” of their depression. Let’s remember, this is a condition with a 15% mortality rate, mainly from suicide.

    Nobody is talking about “suppressing” symptoms. Antidepressants do not “suppress” anything, and there is not an iota of credible evidence that they interfere with one’s learning problem-solving skills while they are being used. Both antidepressants and psychotherapy are useful and effective treatments for severe depression, and probably work synergistically to complement each other.

    It is trivially obvious that people need to work on any underlying psychosocial problems that may be fueling their depression. It is naive and dangerous to assume that we can always identify such underlying issues in all cases. Many people with chronic and severe depression will testify to how good their lives are in all other respects, and that their depression simply comes over them “out of the blue.”
    Intense investigation in treatment often fails to turn up significant “problems” in terms of the patient’s personal, marital, or psychological issues. To insist otherwise in a reflexive and dogmatic way is merely to blame the patient for his or her own depression.

    My suggestion is to put aside the academic theorizing for just a moment, and to read the statement by Rose, a person who wrote in a desperate plea for help on the Psychcentral website. Here is what she said:

    “I have resistan[t] major depression. I suffer constantly, daily with worthlessness, guilt, crying, and helplessness. I have been working with my doctors for years… I have tried suicide and I know it was me reaching out for help…I am desperate for any help. I am a burden for my family and I hate feeling sorry and pitying myself. I just want appropriate help to get this disease cured or at least to achieve relief for myself and my life. Please give any advise… this is a major cry for help. []

    All the clever evolutionary arguments in the world, regarding depression’s “upside” are just a lot of wind,
    when you confront patients with this kind of suffering. And note Rose’s use of the word “disease”. This is precisely the right word for those with serious depression.

    I have seen many hundreds, if not thousands, of patients like Rose over the past 30 years. I have never had one–no, not one–say to me, “Gosh, Doctor, there are some real
    benefits to all this depression!”

    Let’s stop romanticizing a serious illness, shall we? and get on with helping those who suffer with it.

    Ronald Pies MD

  24. #24 Ronald Pies MD
    March 4, 2010


    I would like to clarify my use of the term “Calvinist” in the above blog, since I realize some might take that as a pejorative comment, in a religious context.

    I was alluding to the late Dr. Gerald Klerman’s use of the term “pharmacological Calvinism”,which he applied to an attitude of moral disapproval and condemnation surrounding the use of psychotropic medication. The reference follows. I apologize for any misunderstanding, and I hope the main focus of my posting–the need to treat clinical depression as a serious illness–is clear.

    Hastings Cent Rep. 1972 Sep;2(4):1-3.
    Psychotropic hedonism vs. pharmacological Calvinism.
    Klerman GL.

    Ronald Pies MD

  25. #25 Marian
    March 4, 2010

    @Ronald Pies: Well, you are right when you say that suppress symptoms maybe isn’t exactly what antidepressants do. More precisely, they masque symptoms. I apologize for the inaccuracy. Anyhow, the result is about the same.

  26. #26 Ronald Pies MD
    March 4, 2010

    Another common but erroneous belief is that antidepressants
    “mask” symptoms, but don’t really “treat” them. There is virtually no clinical or experimental evidence to support this notion. It probably stems from the observation that depression is a highly recurrent illness. So, if a patient who was treated with an antidepressant achieves a remission, then has a recurrence three months later, an observer might illogically conclude, “Oh, the antidepressant must have just “masked” the underlying problem.”

    This is no more logical than arguing that if a patient’s cancer returns after a course of successful chemotherapy, that the treatment was merely “masking” the cancer. It is certainly fair to say that the “chemo” was not a cure, just as it is fair to say that antidepressants are in no sense a “cure” for depression–for that matter, neither is psychotherapy. Patients still have recurrences of their depression, even after years of intensive psychotherapy. Does that mean the psychotherapy was just “masking” the problem?

    It is a popular notion that all antidepressants do is “rev up” brain chemicals, like serotonin. This is incorrect. (It is also a view encouraged by much drug advertising, usually under the simplistic rubric that depression is simply a “chemical imbalance”).

    Antidepressants are known to increase various nerve growth factors, such as BDNF, which actually improve connections between neurons in the brain. This is probably why the cognitive difficulties (that’s “difficulties”, not “benefits”)we see clinically in severely depressed patients improve with antidepressant treatment. There are dozens of studies to support this finding.

    This is not a “cosmetic” effect of medication–it is occurring at the most fundamental level, as it involves inducing genes to synthesize new and helpful growth factors.
    Indeed, a recent review of antidepressants and BDNF concludes that antidepressants may lead “ the adjustment of neuronal networks to better adapt to environmental challenges.” [Castren & Rantamaki, Dev Neurobiol. 2010 Feb 22.].

    The “masking” argument is often applied to people with bereavement-related major depression, in which grief is very pronounced along with all the symptoms of a major depression. The argument is, “Medication will interfere with the work of grieving” or will “mask” the underlying grief. There is no credible evidence to support this view.
    Although we need more controlled research, existing studies show that as depression ratings decline with antidepressant treatment, so do ratings of grief [see Zisook et al,
    J Clin Psychiatry. 2001 Apr;62(4):227-30]. If the medication were merely “masking” the grief, we would expect the grief intensity ratings to remain the same, or worsen. This does not happen.

    All this said, I want to be clear that I am not in any way advocating that all major depressive bouts need or merit treatment with an antidepressant. For most mild-to-moderate cases, I would start with psychotherapy. In fact, I have never, in nearly 30 years, recommended medication without urging the patient to be involved in “talk therapy.”

    The peculiar thing about the “upside of depression” argument is that is invites the question, “Why treat major depression at all? Why not just let “nature take its course” and allow the person to reap the marvelous benefits of their enhanced problem-solving abilities?”

    Since nobody advocates this, it is clear to me that the “upside” argument has little or no practical import. If you re-read Roses’s letter, quoted in my earlier posting, you will understand why clinicians believe that it is irresponsible to discourage treatment for severe depression, and potentially life-saving to involve the patient in such treatment.

    Ronald Pies MD

  27. #27 Marian
    March 5, 2010

    @Ronald Pies: I have seen the studies, but I’ve also seen the people. And what I’ve seen in the people is first and foremost a profound alienation. They grieve, but they aren’t aware of it anymore. That may help them “function” again, go to work, be social, forget… Forget. The same effect as ect. Therapy in this case can do one thing: teach people to think what our culture has defined as the “right” thoughts (as in cognitive behavioral “therapy”) . That’s rat-training, not therapy. To solve the problem, you have to be in touch with yourself. No one can be truly in touch with themselves while under the influence of mind-altering drugs.

    The question is, whether we want people to work through and overcome their grief, whether we want them to develop and grow personally, or whether we simply want to “stabilize” them where we think they should be at.

    You mention Rose, who writes she has been working with her doctor for years, and you mention “hundreds, if not thousands, of patients like Rose”. A lot of people for whom the “treatment” you call “effective” obviously does not work. And what do you do? You blame these people: “resistant“. Meaning, if the “treatment” doesn’t work, it’s not the “treatment” something’s wrong with, it’s the person. Their “depression” is “treatment-resistant”.

    You also mention that you have “never had one–no, not one–say” to you they found some benefit to their “depression”. It doesn’t occur to you, that maybe, just maybe, this is because people are indoctrinated from day one that they suffer from a horrible disease that has nothing, absolutely nothing beneficial to it.

    There are at least three people in this discussion, who indeed have found benefits to their suffering, and who did grow personally as a result of this suffering. I know many, many more, who did. The thing is, the mh system didn’t offer them help to do so. So, they had to leave this system, and liberate themselves from its hopeless messages first, and then find real help elsewhere. That these people don’t figure as “successes” in your statistics doesn’t mean they don’t exist. It only means that they weren’t helped by your “effective” treatments.

    Last but not least, I don’t see how acknowledging an upside, whether it is to “depression” or whatever else kind of existential suffering, would invite anyone to think the sufferer doesn’t need help and support. As mentioned, to me it only means that rather than exclusively focussing on pathology in order to fight it, the help and support probably should focus on how the perceived pathology can be turned into an ally in the process of overcoming existential suffering.

    Finally, we do come from very different places. You have observed existential suffering from the scientist’s detached perspective. I have both experienced it myself, and – not as an observing scientist, but simply as a human being – seen other human beings experience it. You see patients and their neurotransmitters, I see people and their lived experience. The difference couldn’t be more profound, so it seems unlikely that we ever will agree on how to view and define “depression” (or “mental illness” in general). The only thing I’d like to ask you is to show just a little more respect and humility towards other people’s lived experience. Disregarded how different from your observations it might be.

  28. #28 Tom Michael
    March 5, 2010

    @Marian – You’ve kind of read my comment correctly. What I was trying to point out is that its hard for anyone, you, me, Pepper, Dr Meh or Dr Pies to be able to really *know* what it feels like for someone else to be depressed.

    I too have suffered from depression, quite badly when I was younger, though thankfully very little in the past few years (apart from last spring, when I became quite depressed for a few months following some very bad relationship troubles). My point is that, even though I understand depression from both a personal perspective, and as a psychologist, I’ll still never really *know* how you felt during the times when you’ve been depressed – you might have felt just like I did, or very differently. Just because two people are behaving the same doesn’t mean they feel the same, or that depression has been caused by the same thing.

    Depression is different from physical illnesses in that it can be described, like much in psychology, as being a biopsychosocial entity. What I mean by that is, that however much medical doctors may argue it is caused by genetics and neurotransmitters (the bio, for which there is much evidence) or psychologists argue that it is caused by thought habits and ways of thinking (the psycho- part, which is treated by CBT, with much evidence) depression is still almost always related to real and genuinely bad things which have happened in peoples lives (the social part).

    Any model of depression, or attempt to understand it which focuses entirely on biological or psychological causes, and neglects the real life social causes of the illness is a poor way of describing the illness. Its also infuriating for people such as yourself (I’d imagine) and me (I know) who have suffered from the illness and know that there are real life causes for the way we have been feeling.

    If there can be said to be anything that is good about depression, I feel this is to do with recovery from depression rather than the awful illness itself. If people are able to recover from depression by re-evaluating their lives and learning to live them in a more positive or resilient way. There’s also something to be said for a spiritual approach to recovering from depression, whatever people’s personal beliefs are, especially if the person has depression as a result of the grief of losing a loved one, particularly under traumatic circumstances. Losing someone you love is a totally real and valid reason to feel miserable, and sometimes despairing – this is why I sometimes feel that to even call depression an “Illness” devalues the real and awful experience that someone is going through, by calling them ill – and I say that as a psychologist as well as someone who has suffered from depression.

    To summarize, we have to remember that depression is BioPsychoSocial – Biological, Psychological and Social in cause and that to neglect any one of these aspects is to do a very poor job of describing what is wrong, or helping people to recover.

  29. #29 Ronald Pies
    March 5, 2010

    “No one can be truly in touch with themselves while under the influence of mind-altering drugs…”

    “The question is, whether we want people to work through and overcome their grief, whether we want them to develop and grow personally, or whether we simply want to “stabilize” them where we think they should be at.”

    1. Major depression is not only drastically mind-altering, it is mind-killing. People die from it. The effects of medication, in concert with psychotherapy, can often help reverse these cognitive problems, as many controlled studies have shown.

    2. The “question” is posed as a classic either/or, false choice. One can overcome one’s grief and grow personally
    while (a) working in therapy and (b) taking an antidepressant. There is not an iota of credible evidence to the contrary, and anecdotal observations of “people” (how many: 10? 100? 1000?) do not constitute credible evidence. To imagine otherwise is simply arrogance.

    3. “You have observed existential suffering from the scientist’s detached perspective….” It’s a shame we need to reduce other people to easy-to-dismiss caricatures, isn’t it? Usually, that happens when our arguments are very, very weak. For more on what existential approaches to grief, sorrow and depression can teach us, please see my article on the PEHM website:

    4. For an elegant dismantling of the “depression is really good stuff” myth (also known as the “analytic rumination” hypothesis), see

    Ronald Pies MD

  30. #30 Marian
    March 5, 2010

    @ Tom Michael: Well, as mentioned, and although I know the feeling of sadness and even despair, I haven’t suffered from these emotions alone to an extent that would have earned me a label of “depression”, but also from fear, anger and confusion to the extent that it earned me the label of “psychosis”. Anyhow, to my conviction both “depression” and “psychosis” are psychological responses to social stressors, and I don’t agree that biology enters the picture as a cause, but merely as just another, somatic, symptom (cf. epigenetics, and research findings that suggest childhood trauma to change both genes and brain structure/wiring), which is a significant difference. – It is not a question about nature vs. nurture, but whether there can be nature without nurture.

    It seems to me that Pepper already very clearly has stated what you say here. I don’t read anywhere in his/her comment that s/he thinks, we should judge other people’s experience. You obviously do. Why? Because s/he has experienced what you think, people shouldn’t be allowed to experience? Who is the one who judges others’ experience here?

    My experience is that my suffering was both the incentive to seek change, and thus to recover, and indeed the map I needed on the path to recovery. What from the outside looked like an illness, I experienced as an attempt to heal from what I regard the real illness: years and years of denial of myself, or my self, if you want, in order to live up to others’ expectations of who and what I should be. So, if ever I have been ill, I was so before I became “psychotic”. That is, during all the years I seemed to be a healthy, functioning person.

    Today, I am grateful to have experienced the suffering I did. And I am especially grateful that I was allowed to own and define my suffering. If I hadn’t been met with that respect, recovery would hardly have been a possibility. To me it is self-evident that no one can heal as long as any attempt to do so is invalidated, labelled an illness in itself, and “treated” (=fought/suppressed).

    Why is it so immensely important to prevent everyone from owning and defining their suffering themselves, and telling them their humanity is an illness they have to fear and fight, when in fact it is the suffering, that is the essence of the human condition, that forms the basis for real recovery to occur?

  31. #31 Marian
    March 5, 2010

    Ronald Pies: “Depression”, major or other, doesn’t kill people. No one has yet died from any “mental illness”. To say anything else is pure sensationalism.

    There’s by now overwhelming evidence that antidepressants hardly ever work better than placebo in regard to symptoms. While there also is overwhelming evidence that they do work unexceptionably in regard to side effects. Among a remarkably long list of side effects there is akathesia, which can lead to suicidality.

    You drew the caricature yourself.

  32. #32 Ronald Pies MD
    March 5, 2010

    As my final entry into this series of exchanges, I’d like to make a few brief points:

    1. I do not respond directly to attacks or critiques by anonymous bloggers, or those who use first names only. Those of us who put our names and reputations on the line every day in our professional writing find such “drive-by” attacks very disturbing.

    2. It is one thing to embrace the supposed virtues of suffering, for oneself; it is another to inflict that view of life on others, as if one is speaking from the moral high ground. This is narcissism masquerading as humanism.

    3. It is true that major depression does not “kill” in the direct way a bullet or a stroke does. Rather, it induces in people a state of suicidal despair and hopelessness, and weakens their usual coping mechanisms, such that many will indeed kill themselves. For families who have lost loved ones to suicide (and I speak from personal experience), it is speciousness combined with callousness to insist that the disease did not directly kill the individual.

    4. Though the issue of antidepressants has nothing fundamental to do with the question of how “adaptive”
    depression is, the notion that antidepressants “hardly ever” work better than placebo is a gross distortion of

    Usually, people who take this position cite the meta-analyses by Kirsch et al and Fournier et al. Both studies are flawed in many ways. The Kirsch et al study looked only at studies done prior to 2000. The Fournier et al study “cherry picked” 6 out of many dozens of studies, selecting only those that failed to control for placebo responders. Two of the 6 studies used sub-optimal doses of

    Nonetheless, both studies clearly found antidepressants superior to placebo for precisely the kind of depression medication was intended: the most severe type. That the effect of medication diminishes as one moves from very severe down to mild depression is not surprising: the closer one comes to “normal sadness”, the less specific the effects of treatment. Furthermore, neither the Kirsch nor the Fournier studies looked at the efficacy of maintenance treatment, which clearly show antidepressants to outperform placebo in maintaining remission. Critiques of these studies may be found at:


    Ronald Pies MD

  33. #33 inverse_agonist
    March 5, 2010

    It’s completely taboo to consider the possibility that depressed people are right. It’s a fact that some people are so alienated that they’ll never fit in. It’s a fact that some people are ugly. It’s a fact that some people die alone. It’s a fact that the world situation with respect to food, energy, climate, and biodiversity is hopeless (it is, don’t kid yourself). It’s a fact that most of how we’re asked to spend our daily lives is empty and meaningless, for many of us. It’s a fact that much of the social sphere in general is shallow and empty.

    Some people realize all these things and conclude, rationally, that it just isn’t worth it to continue. The bright side of things just isn’t worth the bother, on balance. Any discussion of depression is disingenuous without admitting this possibility. The idea that suicide is always irrational is a religious edict, not an objective feature of the universe.

    Yes, we all love beautiful sunsets, but it’s taboo to spend too much time looking at the nasty, ugly, brutish, cruel, and disgusting part of life. Most of us don’t look at photographs of dead children in war zones, or read accounts of torture and sadism. Most of us don’t look at anything that’s too “negative.” Well, the nature of life on this planet is harsh and senseless to a great many people. It’s tragic, and dwelling on it can lead one to despair.

    The absurdity of living in the world and facing social stigma for saying these things out loud just cements the senselessness of the world that much more.

    Yes, it’s genetic and it’s related to stress, social defeat, that sort of thing. At the same time, you aren’t SUPPOSED to waste all your hard won food energy on pointless things. What could be more maladaptive than that?

  34. #34 Marian
    March 6, 2010

    @Ronald Pies: It’s no big deal to find out exactly who I am. A click on my first name here, and voilà. To help you, the full name is Marian B. Goldstein. Does it make a difference? Does it make you any happier to know it? Oh, btw, there’s probably more personal info out there about me, than about you.

    I don’t inflict anything on anyone. I just ask that people have their lived experience respected. No matter if it matches your scheme of things, or not. But I’ve also realized a few comments ago that you seem to think, your title gives you the authority to invalidate others’ lived experiences. Unfortunately a rather common misconception among professionals. But well, so be it.

  35. #35 bariatric surgery
    March 6, 2010

    People who take this position cite the meta-analyses by Kirsch et al and Fournier et al. Both studies are flawed in many ways. The Kirsch et al study looked only at studies done prior to 2000.The argument is, “Medication will interfere with the work of grieving” or will “mask” the underlying grief. There is no credible evidence to support this view.There are the glass half full and the glass half empty people. Rationales for behaviour based on brain biochemistry lead to loss of personal responsibility for your own health. Some people are not depressed by this thought.

  36. #36 Marian
    March 6, 2010

    I wonder what all the professionals who recommend a combination of psych drugs and therapy as the best treatment option would say if their clients had a couple of drinks or smoked pot (or what about some acid, btw??…) right before they turned up for each therapy session. Yeah, I just wonder…

    Ask any half-way meditation-experienced person about mind-altering drugs and enlightenment: it ain’t gonna happen.

  37. #37 Aaron
    March 6, 2010

    I wonder if the field of psychiatry wouldn’t be well-served if its practitioners were to spend a little time ruminating on the source text for this apropos (and cynically presented) slogan:

    “One cubic centimetre cures ten gloomy sentiments.” — Aldous Huxley, Brave New World

  38. #38 Tom Michael
    March 7, 2010

    @Marian – I totally agree with you that its impossible to judge someones first person feelings of how bad their depression was from comments on a blog. That’s why I made the comment that I felt Pepper couldn’t conclude he’d felt just as depressed as Dr. Meh – I basically agree with most of what you have said here.

    Except for one thing though, a small number of people do die from depression, as depression is the cause of their suicide. Its true that this is a small percentage, but Jonah’s latest post notes 20% of psychiatric samples, and that’s pretty bad.

    I won’t comment more here but might comment on Jonah’s latest post 🙂

  39. #39 Marian
    March 8, 2010

    @Tom Michael: There’s a reason — or several ones actually — why I think it isn’t appropriate to over-simplyfy and say that people die from “depression”, or any other “mental illness”. As mentioned, I know about quite a few people who died not in spite of, but because of the “treatment” they received/were subjected to in the mh system. Either they couldn’t stand the side effects and/or the humiliations anymore, and decided to end their suffering — not from the “illness” but from the “treatment” –, or they died from the mentioned side effects of the “treatment”. At least in Denmark where I live, especially the latter deaths are frequently explained away by professionals, who state the cause of death to be “psychosis” in death certificates of people who died while hospitalized/institutionalized. This prevents further investigation into the real cause of death — which more often than not must be suspected to be overmedication — by the authorities, and it is an outrageous practise, if you ask me.

    Another reason why I reject the idea of the potential fatality of “mental illness” to be inappropriate is that it fuels fear in people. It fuels the labelled person’s fear of themselves, their thoughts, their emotions, and it fuels others’ fear of the labelled person, which only contributes to the discrimination against and marginalization of labelled people. My experience is that nothing is more counter-productive in terms of recovery than fear. Fear leads to aggressiveness, and, indeed, what the mh system does today is fight “mental illness”. “What you fight, you strengthen. What you resist, persists.” I’m not surprised, that, by and large, recovery in the mh system doesn’t occur. That I managed to achieve a full recovery from “schizophrenia” is not least due to the fact that I was met with a minimum of fear, if any, by a colleague of yours.

  40. #40 Marian
    March 8, 2010

    …and of course I don’t reject the inappropriateness of the idea of “mental illness” to be potentially fatal, but the idea itself! 🙂

  41. #41 markps2
    March 11, 2010

    re:”If a treatment works for the individual patient that is the only fact that matters. Everything else is mere theory.”

    Patient or prisoner?
    Theory is that psychiatric help is a form of medical help.

    If the patient is not voluntary, the fact then is the person is a prisoner to psychiatry. A prisoner on the precognative ability of a psychiatrist to see a future harm, crime, or medical emergency happening.
    Crime prevention should only occur in obvious psychosis, where a person can not be communicated with, otherwise pre crime is taking away a persons self determination and freewill to chose right and wrong.

    Looking to drugs for a solution might work. Work in the same way a successful alcholic uses the drug alcohol to cope with life.
    Dope dealer of a lesser deadly poison, abusing the “doctor” title of healer.

  42. #42 Rita Bendlin
    February 16, 2011

    I have been diagnose with Bipolar I (manic depression) since 1971. At the time I was going through a divorce, had a set of triplet (2 girls 1 boy) and pregnant with my 4th child, my twin brother was MIA Viet Nam and my ex-husband, gave me no support and was on his own LSD trip with someone of his own kind. My adult family where either dead or did not care or understand that they should. After months of no regular sleep, I broke down and ended up in a pcych ward. The reason I am bring this out. I did not know I was suppose to be depressed. I did not know there was anything wrong with accomplishing many things or doing nothing. I did not know when my husband told me and his friends while they where passing their joint around and wanted to know if I wanted a hit, my husband simple explained: “Rita does not need a hit, she is all ready high” I did not understand I was sick. I just thought this is the way it is. I only see myself now as a self-accomplish person. In some ways, I think of myself as a female Forest Gump. Like Tom Wootton explains, A Black Swan who does not know he is differ from the other Swans. I see life as a situation not a problem. ” It is not the problems you have it is the problems you face up too. I am a Dual Diagnose Counselor now and always been in the public eye. “I am who I am so Let It Be” If it not broken why fix it. If anything I am a victom of Mankind Thoughts. Knowing how many famous people are diagnose with mental illness, gives me a sense of pride. It is just a matter of where and who you are with. Remember “The differants between a Mental Ill Person and a Normal Person. Is they have not caught the Normal’s.” “What is Normal. Being Normal is doing the right thing at the right time. Mother of 6 Grandmother of 14, Great Grandmother of 2. Remember the Keys of the Kingdom, Jesus gave Peter was and is,’Opportunity and Knowledge’ I hope people will always be proud to be a Black Swan. 🙂

  43. wow, there is a lot of people interested in debating and clarifying things. What I wanted to say is a short note reminding you that well, when talking about mental illnesses, we don’t have statistical patients, but unique patients. But we do have to know statistical data,this is where the DSM could become the little Bible that needs to be reinterpreted (again and again until, who knows)You have to remember that being gay/lesbian meant having a mental disease some time ago, so things do change.

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