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Angell’s Review of Psychiatry

Marcia Angell has written a two-part article for The New York Review of Books: “The Epidemic of Mental Illness: Why?” and “The Illusions of Psychiatry.” It is a favorable review of 3 recent books:

and an unfavorable review of the most recent version of the Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR. It paints a disturbing picture of psychiatry. It raises a number of serious concerns but it borders on psychiatry-bashing, a sport that I deplored in a previous post.

Angell has good credentials. She is an MD trained in internal medicine and pathology, a former editor of The New England Journal of Medicine, and is currently a Senior Lecturer at Harvard Medical School. When she speaks, she usually has something interesting to say. In a 1998 editorial she and Jerome Kassirer wrote

It is time for the scientific community to stop giving alternative medicine a free ride… There cannot be two kinds of medicine — conventional and alternative. There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work. Once a treatment has been tested rigorously, it no longer matters whether it was considered alternative at the outset. If it is found to be reasonably safe and effective, it will be accepted.

She has previously criticized the U.S. healthcare system and the pharmaceutical industry in her books Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case and The Truth About the Drug Companies: How They Deceive Us and What to Do About It.

Is There an Epidemic? We are seeing an apparent epidemic of mental illness. 46% of adults are diagnosed with mental illness at some point in their lives. Mental illness is now the leading cause of disability in children, with a 35-fold increase over the last two decades. The tally of those who are so disabled by mental disorders that they qualify for Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI) increased nearly two and a half times between 1987 and 2007—from one in 184 Americans to one in 76.

Is the incidence of mental illness really increasing? Or are we just getting better at diagnosing it? Or have we expanded the criteria for mental illness to where almost everyone can be classified as mentally ill?  It’s not clear.

My skeptical psychiatric consultant, Dr. William Hoffman, comments:

I suspect that the studies overestimate the lifetime prevalence of depression, anxiety, ADHD, etc. either because the diagnostic criteria are sufficiently vague or because normal individuals are incorrectly diagnosed with mental illness (Aragones et al., 2006).  The problem stems, in part, because depression, anxiety disorders and ADHD (this is a subset, but accounts for most of the problem) overlap with sadness, anxiety and inattentiveness that is not pathological. As there is no independent diagnostic test for these disorders, their prevalence depends critically on where the severity line is drawn in the diagnostic criteria.  Tighten the depression criteria and there are fewer depressed people.  Additionally, in clinical practice, diagnostic criteria may simply not be used (Zimmerman and Galione, 2010).

There are several forces that drive looser diagnostic criteria (Mulder, 2008):

  1. Pharmaceutical companies certainly benefit from more inclusive criteria, higher prevalence rates and more prescriptions written. An indication for depression is a gold mine for a pharma company; witness the stampede to get depression indications for antipsychotics. Industry influence can be felt in the design of clinical trials, industry supported education of providers (remember, most antidepressants are prescribed by primary care providers) and direct marketing of the drugs.
  2. Looser diagnostic criteria can give the illusion that the clinician is helping more people. Coupled with the (almost certainly erroneous) belief that pharmacotherapy is at worst harmless, this leads to prescriptive practices treat people who do not even meet the permissive DSM-IV criteria (“Dr. Hoffman, why would you deny this patient the possibility that Superdrug might help them? Can’t you see that she’s suffering?”).
  3. Permissive criteria also indirectly foster the clinical impression of efficacy. Normative sadness is by definition a time limited phenomenon and, if a sad person is treated with an antidepressant, they certainly cease being sad sometime after drug initiation. Clinicians don’t have as much experience with sad people who weren’t treated with drugs and got better sometime after the decision to withhold pharmacotherapy.

It’s reasonable to hypothesize that permissive diagnostic criteria are responsible for the high rate of failed trials of antidepressants and of the meta-analytic finding that ‘mild’ depression responds to antidepressants no better than to placebo. There are other possible (not mutually exclusive) explanations for these findings (diagnostic heterogeneity, e.g.), but criterion creep probably accounts for a lot of the problem.

How much are pharmaceutical companies to blame? The three authors agree that the pharmaceutical industry has unduly influenced our thinking about diagnosis and treatment. Studies have shown that psychiatrists receive more money from pharmaceutical companies than physicians in any other specialty. In his book, Carlat explains that psychiatrists are an easy target because

Our diagnoses are subjective and expandable, and we have few rational reasons for choosing one treatment over another.

It is illegal for pharmaceutical companies to encourage off-label prescription in their marketing efforts. Several firms have been charged with such offenses in recent years. Angell thinks the laws should cover not just companies, but physicians. She says:

I believe doctors should be prohibited from prescribing psychoactive drugs off-label.

I disagree. Sometimes off-label indications are justified by published evidence before formal approval is obtained. A blanket prohibition on off-label prescribing would slow the incorporation of new knowledge into clinical practice and would be an unwarranted interference with physician autonomy and clinical judgment.

Financial considerations affect individual providers and patients as well as pharmaceutical companies.

Like most other psychiatrists, Carlat treats his patients only with drugs, not talk therapy, and he is candid about the advantages of doing so. If he sees three patients an hour for psychopharmacology, he calculates, he earns about $180 per hour from insurers. In contrast, he would be able to see only one patient an hour for talk therapy, for which insurers would pay him less than $100.

Children are increasingly being given psychoactive drugs that have not been studied in children. Children from low-income families are four times as likely to be on these drugs. SSI income is a strong incentive for labeling them with a qualifying diagnosis.

Are These Diseases Caused by Chemical Imbalance? None of the three authors subscribes to the popular belief that mental illness is caused by a chemical imbalance in the brain.  Indeed, the evidence for it is very shaky.  All we really know for sure is that the chemistry of the brain changes in patients on medication.

My psychiatric consultant Dr. Hoffman agrees that the chemistry imbalance hypothesis is simplistic, misleading, and essentially wrong. However, he argues that this is not a reason to abandon psychoactive medications:

This is not to say that major depression, anxiety disorders and ADHD don’t exist or that no one should be treated with psychotropics for these disorders. Severely depressed people, e.g. those with melancholia, do not improve in a short time, are markedly unresponsive to normal rewards, have group differences in fMRI responses and are much more likely to respond to pharmacotherapy and much less likely to respond to placebo (Heinzel et al., 2009; Horn et al., 2010).  Are patients with melancholia qualitatively different from more mildly unhappy people? That is, does the mechanism by which they are unhappy differ from more usual sadness? Do they have a ‘chemical imbalance’? Let’s look at a more straightforward example.

Schizophrenia is a brain disease. ECA (Epidemiologic Catchment Area) estimates of the prevalence of schizophrenia have not changed. The prevalence of schizophrenia is the same (about 1%) in every human culture and ethnic group. The phenotype of schizophrenia is markedly different from normality and does not overlap much with normal behavior. Schizophrenics as a group have many biologically replicable differences from non-psychotic individuals, although the pathognomonic diagnostic test eludes us still. This qualitative and quantitative difference is reflected in the lower rate of failed clinical trials of antipsychotics and the very low rate of placebo response. Is schizophrenia due to a ‘chemical imbalance’?

Nope. But then, neither is any other neuropsychiatric disorder.

Schizophrenia is one of the most intensely studied neuropsychiatric disorders. No credible neuroscientist doubts that the schizophrenic syndrome arises from genetically influenced brain abnormalities present at birth that interact with subsequent brain development and environmental contributors in a manner that increases the risk of undergoing a psychotic transition sometime in adolescence or early adulthood. Dopamine D2 family antagonists are the only (even partially) effective treatment for some of the symptoms. Despite three decades of looking, there does not seem to be a large primary abnormality in the dopaminergic system in schizophrenics’ brains. Contemporary conceptions of schizophrenic pathology concern abnormalities in brain circuitry (Swerdlow, 2011).  DA modulates the function of some of those circuits and, through this mechanism, DA blockade exerts its influence. Greater DAergic stimulation (like by cocaine) makes schizophrenic symptoms worse and DA blockade makes it a bit better, but the actual state of affairs is quite complex and not due to a simple chemical imbalance.  Depression fits this simplistic model even more poorly, particularly because depression (perhaps of lesser severity) will respond to psychosocial interventions while schizophrenia does not.

Borderline personality disorder, another syndrome that is relatively reliably (don’t know yet about validity) defined responds poorly to drugs and best to specific psychosocial interventions (Gunderson, 2011; Leichsenring et al., 2011). Does response to non-pharmacologic interventions mean that the disorder under consideration is not a brain disease? Does this mean that the individual is somehow more responsible for their disorder than someone with, say Parkinson’s disease? Certainly not. The affective, behavioral and cognitive dysregulation in borderlines is based on genetic and developmental variance from the norm. No one would choose borderline personality disorder as a lifestyle.  It’s just that that disorder, like milder depression, occurs in a brain that is able to respond to techniques that get the patient to practice behaviors that preclude their more troubling symptoms.

This is a source of some confusion and is reflected in some of the authors’ work in the review. Just because the chemical imbalance model is too simplistic (or just plain silly) as an explanation of a disorder does not suggest that the disorder doesn’t exist or imply that (and this is never explicitly stated, only implied) the disorder is not really dependent on brain function in the same way as, say, Parkinson’s Disease. To the extent that the disorder can be reliably diagnosed and has adequate validity (one could readily argue that some DSM-IV disorders lack validity), it must, of necessity, reflect variant brain function.

So why does the model persist? William Hoffman again:

There are many reasons why the chemical imbalance model persists despite no real evidential support of its primary form. Busy clinicians like simplicity. It frees them from uncertainty and provides a guide to purportedly healing actions. A common complaint from psych residents about presentations of the neurobiology of psychiatric disorders is, “But how does this neuroanatomical circuit stuff tell me what to do?” And it doesn’t always tell clinicians what to do, although sometimes it might tell them what to avoid. If one can go through the depression checklist, determine that the person meets criteria, prescribe the first antidepressant on the algorithm (or the miracle drug discussed at the drug dinner last night) and then move on to the next person, one can avoid the anxiety of saying, “Ms. Smith, it sounds like you’ve had a tough time lately. A lot of people react with feelings of sadness in this situation. But most people also pull out of it without having to use antidepressants. I’d like to prescribe an activity schedule that will get you out of the house and doing some of the things that you enjoy. I’m glad you identified a friend who’d be willing to be a short term coach and get you out even when you don’t feel like it. I’d also like you to see Dr. X, who can teach you some new mental techniques that have been shown to help with your kind of sadness. You’ll see him twice a week at first and I’d like you to meet with our activity therapist to review your activity schedule. I’ll see you in a couple weeks to see if you’re able to benefit from this plan.” That’s a complex plan and, because it involves extra visits, it might be more expensive than saying, “Here are some samples of Sliced Bread and a prescription for when those run out. Antidepressants take about three weeks to start working, so I’ll see you for 15 minutes in three weeks.” Pharma is able to exploit clinicians’ desire to help patients and their anxiety in the face of scientific indeterminacy with drugs (Newer! Better! More powerful! [More expensive]) and a plan for their use.

How do psychiatrists arrive at a diagnosis?

[Carlat’s] work consists of asking patients a series of questions about their symptoms to see whether they match up with any of the disorders in the DSM. This matching exercise, he writes, provides “the illusion that we understand our patients when all we are doing is assigning them labels.” Often patients meet criteria for more than one diagnosis, because there is overlap in symptoms.

How do psychiatrists decide which drug to prescribe? Carlat says:

Guided purely by symptoms, we try different drugs, with no real conception of what we are trying to fix, or of how the drugs are working. I am perpetually astonished that we are so effective for so many patients.

Are psychoactive drugs merely placebos? Kirsch has been on something of a crusade to prove that hypothesis. His interpretation of the data on anti-depressants differs from Erick Turner’s interpretation of the same data because of a different understanding of effect size., as I explained in a previous post.

Studies showing that psychoactive drugs are more effective than placebo do not show a very large difference, and it has been speculated that the side effects of these drugs reveal to the patient that he is not getting a placebo, thereby enhancing the placebo effect of the drug. Studies using an “active” placebo that causes side effects seem to support this hypothesis. But a more definitive way to test it would be to do an “exit poll” asking subjects whether they thought they had been assigned to the placebo group or the drug group. In acupuncture studies, subjects who believed they were in the true acupuncture group improved more than those who believed they were in the control group — no matter which group they were actually in! As far as I know, no similar studies have been done for psychoactive medications.

Are these drugs harmful? Whitaker argues that psychoactive drugs may be responsible for turning episodic illness into chronic illness. He says antipsychotic drugs shrink the brain. By altering brain chemistry, they may cause disease. For instance, anti-depressants can cause episodes of mania resulting in a new diagnosis of bipolar disorder. He thinks we are seeing an iatrogenic epidemic of brain dysfunction. It can be difficult to get off the drugs because the brain has adapted to their presence. He particularly demonizes Zyprexa. His arguments are not convincingly supported by evidence, but they do suggest directions for research.

Is the DSM based on science? It appears to be strongly influenced by opinion. It is disturbing that the number of diagnoses keeps increasing, from 182 to 365.

Even Allen Frances, chairman of the DSM-IV task force, is highly critical of the expansion of diagnoses in the DSM-V. In the June 26, 2009, issue of Psychiatric Times, he wrote that the DSM-V will be a “bonanza for the pharmaceutical industry but at a huge cost to the new false positive patients caught in the excessively wide DSM-V net.”

As Angell says,

It looks as though it will be harder and harder to be normal.

The DSM is a noble but flawed effort to standardize psychiatric diagnosis and make it more rational. I’m afraid we are stuck with it. It won’t go away, but we can hope to make it better and more scientific. Despite its flaws, it’s arguably better than going back to pre-DSM days.

Are non-drug options preferable? Angell argues that:

At the very least, we need to stop thinking of psychoactive drugs as the best, and often the only, treatment for mental illness or emotional distress. Both psychotherapy and exercise have been shown to be as effective as drugs for depression, and their effects are longer-lasting.

Yes, but. Non-drug options are not effective for the most severe cases. Psychotherapy can be next to impossible in severely impaired patients, and drug therapy must be added to enable them to respond and cooperate with psychotherapy. And how successful has anyone ever been in getting a severely depressed patient to go out and exercise? Sometimes they can’t even get out of bed.

Conclusion

Angell calls the books she reviews “powerful indictments of the way psychiatry is now practiced.” Indictments have their place, but we mustn’t ignore all the things modern psychiatry gets right. It has (mostly) rejected Freud and is making a valiant effort to become more evidence-based. It has prevented suicides, alleviated incapacitating symptoms, and helped patients enjoy a reasonably normal life at home instead of in a locked ward. Instead of throwing out the baby with the bathwater, how can we employ common sense and rigorous science to improve psychiatric care? Neither Angell nor the books she reviews offer any concrete proposals for improvement. Angell says one thing I can heartily agree with:

Our reliance on psychoactive drugs, seemingly for all of life’s discontents, tends to close off other options… we need to do better.

Hear, hear!

Acknowledgement: Thanks to Dr. William Hoffman for his input. He is a psychiatrist at the Portland VA Medical Center and the Oregon Health & Science University.

Disclaimer: Dr. Hoffman’s opinions expressed herein are his alone and not the opinions of the Department of Veterans Affairs, OHSU, or his cat.

Reference List

Aragones E, Pinol JL, Labad A (The overdiagnosis of depression in non-depressed patients in primary care. Fam Pract 23:363-368.2006).

Gunderson JG (Clinical practice. Borderline personality disorder. N Engl J Med 364:2037-2042.2011).

Heinzel A, Grimm S, Beck J, Schuepbach D, Hell D, Boesiger P, Boeker H, Northoff G (Segregated neural representation of psychological and somatic-vegetative symptoms in severe major depression. Neurosci Lett 456:49-53.2009).

Horn DI, Yu C, Steiner J, Buchmann J, Kaufmann J, Osoba A, Eckert U, Zierhut KC, Schiltz K, He H, Biswal B, Bogerts B, Walter M (Glutamatergic and resting-state functional connectivity correlates of severity in major depression – the role of pregenual anterior cingulate cortex and anterior insula. Front Syst Neurosci 4.2010).

Leichsenring F, Leibing E, Kruse J, New AS, Leweke F (Borderline personality disorder. Lancet 377:74-84.2011).

Mulder RT (An epidemic of depression or the medicalization of distress? Perspect Biol Med 51:238-250.2008).

Swerdlow NR (Are we studying and treating schizophrenia correctly? Schizophr Res 130:1-10.2011).

Zimmerman M, Galione J (Psychiatrists’ and nonpsychiatrist physicians’ reported use of the DSM-IV criteria for major depressive disorder. J Clin Psychiatry 71:235-238.2010).

Posted in: Book & movie reviews, Neuroscience/Mental Health

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273 thoughts on “Angell’s Review of Psychiatry

  1. Tell it like it is says:

    As time marches on and our attitudes and understanding of our ‘self’ improves, what we believe now become irrelevant fossils of a bygone age – no more than curious relics – like all beliefs.

    We laugh when we read about the prudishness of high Victorians who clothed piano legs in stockings so that they would not appear too suggestive and still we draw swords and squabble and fight over differences – and these very differences inhibit man’s progress towards atonement*.

    Any given paragraph that I or our other comrades on this site submit, can be read in a variety of ways: wise, cynical, ribald, witty, fantastic, irreverent, manipulative, and cynical by turns.

    The only tones that we choose to avoid for the most part, are the smirking and the lascivious. Smirking is avoided because we will bring shame to the smirker as we continually wipe the grin off their face; and lasciviousness is avoided because the prudish would still like to clothe piano legs in stockings so that they would not appear too suggestive.

    So why do we persist with our merrie banter? I believe the reason for this is because strong words have the ability to break through our boundaries and shock us into new perceptions. T S Elliot wrote “We shall not cease from exploration. And the end of our exploring is to arrive where we started from – and know the place for the first time.”

    We do not exclude science from this exploration – and yet here we seem to exclude TAM et al and treat them as the enemy; and rather that help them past ‘their’ delusions, and they in turn help ‘scientists’ past theirs; we choose instead to take the stance of the sophist** and the solipsist#. And they do exactly the same. We are not all directly related to Hamlet – or any other fictional character, but we are all related to Shakespeare.

    Most of us are ‘not’ sophists or solipsists and so for the most part, we do not do bring new perspectives by deliberately shooting something down because we have some sort of aversion to it; rather, we do it through a transformative and informative mission of peace and reconciliation, and in so doing we advance our knowledge.

    In an attempt to establish belief in his ‘survival of the fittest’ idea, Charles Darwin chose the fantail pigeon to conclusively demonstrate proof. He systematically ‘culled’ (killed) many generations of birds that did not have the ‘desired’ ‘pure-strain’ fantail characteristic that Darwin sought. In the process, Darwin enjoyed many many years of frustration that turned his beard and eyebrows white.

    Something spectacular blatantly stared Darwin in the face – but he couldn’t ‘see’ it. What Darwin failed to see, and so missed a trick, was that the pigeons Darwin was ‘eradicating’ were not ‘false negatives’ (as we perceived he believed), what his ‘death’ records show is that the CULLED pigeons EXACTLY FOLLOWED THE LAWS OF GENETICS – but Darwin, in his single-minded ‘I am right’ obsession and misconception with ‘survival of the fittest’ paradigm, was looking the wrong way and so he meandered along the wrong line of enquiry.

    This scuppered progress for almost a century until James Watson the American prodigy, and the Brit Francis Crick came along with a radical approach to understanding the situation that presented itself – that of genetics.

    The balance between accuracy and replication ‘error’ is a fine one. Too many errors and organisms cannot function properly and we observe autism et al. Insufficient ability for the DNA to recover from an error and we slowly regress ‘and’ sacrifice adaptability. Mendel observed this ‘degeneration of species’ when he moved from plants to insects, and then to creatures. His cross-breeding produced killer bees and ‘dippy’ cats.

    Because of the embarrassment of Darwinists, it took the sceptical world another twenty-five years before Watson and Crick finally had their discovery accepted in 1986.

    A good leader is a leader for ‘good’ so that we may get to know one another – so that when we finally shuffle off our mortal coils, we leave this place a better place than when we found it.

    Stop the bickering and properly address the problem.

    TILIS

  2. Tell it like it is says:

    This is the footnote – please skip if not required Cheers.

    * The word ‘atonement’ is a special word that has ‘two’ meanings contained within it. These meanings are revealed depending upon how you ‘pronounce’ the word. When pronounced as ‘a-TONE-ment’ it refers to divine punishment that is inflicted upon one because of our misdeeds – the ‘God never pays debts back in money’ allegory. When pronounced as ‘at-ONE-ment’ it refers to mankind’s spiritual quest to seek at-one-ment with the universe.

    ** Sophists are a devious bunch of people who goad others through fallacious and salacious reasoning. Because sophists lack the intelligence to discuss the merits of a philosophical argument, their aim is to use brinkmanship in an attempt to outwit their opponents so as to win an altogether different argument. Their techniques include: using BS, HS, and BE; misdirection; questioning the motive of the person making the argument; attempting to deflate the opposition by exaggerating the propositions stated; and misrepresenting the other person’s words. Humpty Dumpty is a sophist.

    # Solipsists are people who believe that only ‘they’ exist, and life is played out as a ‘virtual-world’ film (movie) which they watch, and in which they ‘appear’ to participate. The moment a solipsist walks out of a ‘scene (e.g. the kitchen), that kitchen no longer exists. I am not exactly certain what happens when you place one foot in the kitchen and the other in the adjacent room – best not ask.

    ‘The Matrix’ trilogy is all about solipsism.

    We encounter solipsism in ‘Alice through the looking glass and what she found there’. When Alice meets the Tweedles – two brothers – one called Dum (dumb – but not) and one called Dee (after fiddle-de-dee, the modern colloquialism of which is ‘whatever’ = believe what you want).

    Alice is participating in a chess game and she sees the Red King who is asleep. Alice is questioned as to what would happen if she was to awaken him and Tweedle Dee informs Alice that Alice is part of the Red King’s dream and therefore it would be impossible for her to stir the King from slumber.

    “He is dreaming now” said Tweedledee: “and what do you think he is dreaming about?” “Nobody can guess that” says Alice. “He’s dreaming about ‘you’ … and if he left off dreaming where do you suppose ‘you’ would be? “Where I am now of course”, said Alice. “If that there King was to wake” added Tweedledum – “you’d go out like a candle”.

  3. Shelley says:

    I am a cognitive behavioral therapist, and CBT works very well for depression, mood, and anxiety disorders. However, when people are profoundly depressed or anxious, getting them to move to do even the smallest thing can be exceedingly difficult. Medication will often lift mood sufficiently that we have something to work with.

    I’m fortunate to work in a team environment and have available a combination of medication and/or CBT or talk therapy depending on the nature of the depression/anxiety (which is sometimes simply situational) and the clinical disposition of the physician. Some physicians use all of the resources available. Others only prescribe and never use CBT or social work.

  4. Harriet Hall “Is There an Epidemic? We are seeing an apparent epidemic of mental illness. 46% of adults are diagnosed with mental illness at some point in their lives.”

    Wow that’s horrible.

    Wait.. how many people get diagnosed with physical illness in their life?

    As an aside, I was told by one of my therapists that many mental disorders, like mild depression, anxiety disorders, etc are not considered “mental illness”. That term is generally reserved for the more severe life threatening disorders like bipolar and schizophrenia. Of course that is semantics, but I do wonder if most people would find that number less shocking if they knew of all the individual circumstances and diagnoses that make up that number.

  5. colli037 says:

    Very nice article, but neglected one key factor in all of this:

    The mildly “ill” patients demand to “fix this with a pill”. My experience in this field suggests that the vast majority of patients either deny there is any problem at all, or do not want to do not want to expend any effort at all.

    The need to treat with a simple pill in a short time is not driven entirely by the physician, but also the demand from the patient, who with rare exceptions would rather come to the doctor for 15 min. every 2-3 months, rather than 30-60 minutes every week.

    tim

  6. passionlessDrone says:

    Hello friends –

    Nice article, but I’m a bit confused by the resistance of mental disorders having a basis in altered brain chemistry. Maybe it is a semantics issue (?), and I’m not trying to (intentionally) subscribe to an over simplification, but some of these statements don’t seem to jive with what (I think) I’ve read, or even each other.

    All we really know for sure is that the chemistry of the brain changes in patients on medication.

    Don’t we also know that there are differences in brain chemistry in these populations without taking medication, also?

    Whitaker argues that psychoactive drugs may be responsible for turning episodic illness into chronic illness. He says antipsychotic drugs shrink the brain. By altering brain chemistry, they may cause disease

    Isn’t this rather inconsistent with the idea that disorders aren’t chemically based?

    The ‘neuroanatomical circuit stuff’ is all about the reliable, or unreliable transport of chemicals. If the data on chemical mediated disorders is so sparse, I didn’t see anything in this article indicating a preferred explanation. Does anyone have any insight or alternative theories they would be wililng to share? What am I missing here?

    Nice article. Thank you.

    - pD

  7. cervantes says:

    You say that Whitaker’s assertion that psych meds can actually cause disease is not well supported by evidence. (It’s actually a bit more accurate to say that he claims they can exacerbate it and prevent normal remission which is the expected outcome of ordinary depression and often happens, in fact, in untreated psychosis and bipolar disorder.) This is an airy dismissal of what is in fact quite a well-documented and strongly reasoned argument.

    Whitaker’s claim is difficult to process to be sure — it is extremely disturbing. He asserts that drug treatment is literally destroying millions of lives by turning what would otherwise be self-limiting problems into severe, chronic diseases. This is far more plausible than you would like to admit, I think. As you concede, people diagnosed with depression, for example, do not have any identifiable abnormality of neurotransmitter levels until after they have been on antidepressants for several weeks. Antidepressants do not treat any known abnormality, they cause abnormalities of brain functioning. This is a cold fact. When people stop taking them, they often have severe withdrawal symptoms because the brain no longer produces sufficient serotonin and has fewer serotonin receptors. This causes rebound depression, so people need to keep taking the drugs in order to stay more functional, in spite of the often quite significant side effects.

    Evidence for the efficacy of antidepressants is based on very short term studies — and it is extremely weak nevertheless. Due to selective publication by the manufacturers this was not fully recognized until fairly recently, but now meta-analyses based on all the available studies fail to find any benefit at all except for the most severe, intractable depression. Although there are problems with confounding by indication, longer term observational studies find better outcomes with unmedicated people.

    BTW Whitaker also asserts that antidepressants cause bipolar disorder in people who originally present only with depression. He makes a strong argument there as well. In the interest of space I will pass over his discussions of schizophrenia, anxiety, and childhood diagnoses, but they also compel respect.

    Whitaker notes that Scientologists are the best friends the psychopharmaceutical-psychiatric complex, if you will, ever had. They can just say “the people making these claims are followers of a wacko cult” and don’t have to actually address the evidence and answer the arguments. That’s what they have been doing. But I think this is a very serious, credible set of hypotheses that compels dispassionate consideration and investigation. We could be creating a vast human catastrophe, as a result of medical science being distorted by pecuniary interests. it is inappropriate and unbecoming simply to dismiss it.

  8. Scott says:

    Nice article, but I’m a bit confused by the resistance of mental disorders having a basis in altered brain chemistry.

    I don’t think there is. What’s resisted is the simplistic idea that (for instance) depression is caused by an “imbalance” of having too little serotonin. Is brain chemistry involved in (at least some) mental disorders? Very likely. Is it that simple? Definitely not.

    That’s how I read the post, anyway.

  9. psychability says:

    Legitimate research has demonstrated that antidepressants work poorly in people who are “sad” or “nervous”. Therefore giving a grieving or stressed person an antidepressant is unlikely to have an outcome better than placebo. The meds have more effect in what we used to call melancholic depression – you would never mistake these people for being just sad, they are ill.

    While broadening diagnostic criteria may have provided a larger pool of subjects for antidepressant trials, it has also backfired in that these people are more likely to be non-responders, making the drugs appear to be less effective.

    The medicalization of unpleasant emotions has obfuscated the drug research, prevented many people from living their lives and has greatly embarrassed psychiatry.

  10. passionlessDrone says:

    @ scott –

    I wish I’d seen the ‘chemical imbalance’ hypothesis as strictly defined here. I am in agreement with your position, and the difficult to defend nature of ‘a lack of serotonin causes depression’ model.

    @ cervantes –

    As you concede, people diagnosed with depression, for example, do not have any identifiable abnormality of neurotransmitter levels until after they have been on antidepressants for several weeks.

    I didn’t see that anywhere in the article. Can you provide a link to substantiate this?

    Antidepressants do not treat any known abnormality, they cause abnormalities of brain functioning. This is a cold fact.

    I would be interested in your thoughts regarding the apparent anti-inflammatory nature of many anti-depressants.

    I tend to like what I think is your gist, the very real problems with jiggering around with neurotransmitters acting like we have a clue about what we are doing, but I didn’t see anything here indicating there were no imbalances in neurotransmitters pre-treatment. I am especially concerned about this in children, many of whom are getting multiple types of agents, which I very highly doubt we can understand the interactions with inside the developing brain.

    - pD

  11. Geoff says:

    Having seen many individuals reverse minor to relatively severe levels of depression and other mental illness through dietary intervention, so I feel pretty confident that it is a chemical imbalance. That’s not to say that the current chemical imbalance model isn’t or cannot be wrong. Just that I have seen people get their biochemistry in order and see dramatic improvements in mood as a result, and that I find it pretty implausible that it is in any way “natural” for people to experience chronic sadness.

    Tragedy has always been a huge part of human life, from a 20% infant mortality rate to infectious disease to animal attacks, historically we have always lived brutish lives that involved facing death on a very frequent basis. If “chronic sadness” could occur in a healthy brain, it would have been selected against.

    The psych literature is full of evidence suggesting that intestinal and blood brain barrier permeability play a significant role in brain biochemistry issues, and I suspect that there are other issues at play as well, including certain amino acids missing from the diet that are precursors to neurotransmittors, and imbalances in n-6/n-3 PUFA.

    Metabolic derangement seems to also change the way that amino acids are metabolized into neurotransmitters. For example, I know that an inflammatory state causes tryptophan to be converted disprortionately to kynurenic acid rather than seratonin. All of this points to the idea that lifestyle factors, including food, but also sleep, exercise and sunlight, play a significant role in the chemistry of the brain, as they to in the chemistry of the body.

  12. Scott says:

    Having seen many individuals reverse minor to relatively severe levels of depression and other mental illness through dietary intervention, so I feel pretty confident that it is a chemical imbalance.

    [Citation needed]

  13. qetzal says:

    Shorter TILII, after stripping out the parts that are irrelevant to the actual topic:

    {} (the empty set)

    BTW, Watson and Crick did not discover genetics. They determined the 3D structure of double-stranded DNA. And any suggestion that their discovery wasn’t accepted until 1986 is just ludicrous. They published their structure in 1953 and were awarded a Nobel Prize for it in 1962!

  14. LovleAnjel says:

    What portion of the increase in diagnosis could be attributed to the change in attitude towards mental illness in our society? It seems like it is less shameful to be diagnosed now than, say, 30 years ago. Also the prevalence of direct-to-consumer marketing probably increased the number of people seeking help (not necessarily asking for a pill, but thinking, oh maybe I should go see someone about this). Increased awareness + decreased shaming would seem to increase diagnosis by getting more people through the door in the first place.

  15. Geoff says:

    @Scott

    That was anecdotal. I could introduce you if you’re interested. My friend John is at the top of that list: http://hunter-gatherer.com/.

  16. cervantes says:

    Passionless drone — Whitaker’s book is very well documented. He has posted all of his references on-line:

    Anatomy of an Epidemic

  17. Scott says:

    @ Geoff:

    If it’s anecdotal, then (a) you don’t know that dietary intervention had anything to do with it, and (b) you shouldn’t “feel pretty confident” that it tells you anything about the mechanisms.

  18. cervantes says:

    Just to give people an idea of the extent of the documentation Whitaker provides free, on-line, I’m going to paste an excerpt here. People who really want to follow this up can check it out for yourselves, read the literature, and decide whether he has a case worth considering. (See my previous post for the link.)

    “A. The Natural Course of Depression

    Prior to the widespread use of antidepressants, the National Institute of Mental Health told the public that people regularly recovered from a depressive episode, and often never experienced a second episode. As the NIMH’s Jonathan Cole wrote in 1964: “Depression is, on the whole, one of the psychiatric conditions with the best prognosis for eventual recovery, with or without treatment.” Given this understanding of the natural course of depression, the NIMH’s experts believed that antidepressants might shorten the time to recovery, but they wouldn’t be able to boost long-term recovery rates. The reason, explained Dean Schuyler, head of the depression section at the NIMH, in 1974, was that most depressive episodes “will run their course and teminate with virtually complete recovery without specific intervention.”

    B. The Chronicity Problem Appears

    Once psychiatrists began treating their depressed patients with antidepressants, at least a few observed that these patients, once they got better and stopped taking the drugs, regularly became depressed again. While the drugs might help people over the short-term, they were putting them onto a more chronic long-term path.

    1. Recurrent vital depressions. Van Scheyen, J. Psychiatry, Neurologia, Neurochirugia 76 (1973):93-112.

    After reviewing the literature and conducting his own study, Dutch investigator J.D. Van Scheyen concluded that “more systematic long-term antidepressant medication, with or without ECT, exerts a paradoxical effct on the recurrent nature of the vital depression. In other words, this therapeutic approach was associated with an increase in recurrence rate and a decrease in cycle duration.” As he noted, other psychiatrists had observed that antidepressants were causing a “chronification” of the disease.

    C. The High Relapse Rate After Exposure to an Antidepressant

    During the 1970s and 1980s, the NIMH and other groups reported that patients withdrawn from antidepressants “relapsed” at high rates.

    2. An evaluation of continuation therapy with tricyclic antidepressants in depressive illness. Mindham, R. Psychological Medicine 3 (1973):5-17.

    British researchers found that 50% of drug-withdrawn patients relapsed within six months.

    3. Maintenance therapy with amitriptyline. Stein, M. American Journal of Psychiatry 137 (1980):370-1.

    Investigators at the University of Pennsylvania reported that 69% of patients withdrawn from an antidepressant relapsed within six months. There was “rapid clinical deterioration in most of the patients.”

    4. Drug therapy in the prevention of recurrences in uinpolar and bipolar affective disorders . Prien, R. Archives of General Psychiatry 41 (1984):1096-1104.

    Robert Prien at the NIMH reported that 71% of depressed patients relapsed within 18 months of drug withdrawal.

    5. Course of depressive symptoms over followup. Shea, M. Archives of General Psychiatry 49 (1992):782-87.

    In an 18-month NIMH study that compared four types of treatment (two forms of psychotherapy, an antidepressant, and placebo), the group that was initially treated with the antidepressant had the lowest stay-well rate by the end of the study.

    6. Discontinuing antidepressant treatment in major depression. Viguera, A. Harvard Review of Psychiatry 5 (1998): 293-305.

    In a meta-analysis of the relapse literature, Havard researchers concluded that at least fifty percent of drug-withdrawn patients relapsed within 14 months.”

  19. Diomedes says:

    While I would agree that there are many criticisms of psychiatry that are well founded, it has become too easy to judge the field. If we even accept that mild depression or anxiety are real disorders (apparently dubious), they simply are not as serious as bipolar disorder, schizophrenia, or severe depression. Do we judge dermatology because there are still teenagers with acne? Or do we judge dermatology by its ability to treat leprosy or leischmaniasis, much more severe ailments?

    The ability to treat patients with bipolar disorder, schizophrenia, and severe depression (melancholia) has been greatly improved by the availability of lithium, antipsychotics, and antidepressants. And the fraction of the population with these serious illnesses has not changed, solid evidence that these are real disorders with a real physical basis.

    People with mild depression and anxiety are not the sickest patients, and may not even really be good candidates for medication at all. Meanwhile, there are genuinely seriously ill patients that are not getting the treatment they need, largely due to lack of access. I know who I’m worried about, and it ain’t the vaguely unhappy.

  20. passionlessDrone says:

    Hello friends –

    I took a look at some of the references on Whitaker’s site. Here’s something from the children page.

    At the end of six years, medication use was “associated with worse hyperactivity-impulsivity and oppositional defiant disorder symptoms,” and with greater “overall functional impairment.

    That’s pretty astounding stuff! Unfortunately, it is highly cherry picked. From the actual paper, also available on Whitaker’s site.

    Medication use in the past year, measured at each
    assessment and treated as a time-varying covariate, was
    associatedw ith outcome over time in a pattern consistent
    with previous studies. It was associated with symptom remission at 74 and 24 months, when medication use mostly reflected randomized treatment group assignment, but it was associated with worse hyperactivity-impulsivity and ODD symptoms and CIS impairment (or showed no association with other continuous variable repeated-measureos utcomes) at 6
    years. Most associations were not significant at 8 years. An exception occurred for math achievement. Past-year medication and math scores were positively associateadt 3 6 months( p = .0011)6, years(p = .0002),
    andB years(/ . .OOOtb) ut not ar 14o r 24 months( p>
    .05). Because past-year medication use at the later
    assessments generally reflected continued and not newly
    initiated medication, these findings suggest a uniquely
    beneficial effect oF continued medication treatment on
    math achievement.
    These associations were present
    whether inirial randomized treatment group assignmenr
    was included in the model
    (my emphasis)

    So, we see more hyperactivity at six years, and no change at eight years, except better math scores. To me, this sounds like noise more than anything else.

    I think that the .pdf was a scanned copy or something, which accounts for the sketchy copy/paste value above. Considering this was the first paper I decided to look at, and came back with data that largely contradicts the finely tuned snipet on the Whitaker page, I’m getting a sinking feeling about some of the larger points he’d like us to believe he has culled from his analysis of the literature.

    What to believe?

    - pD

  21. passionlessDrone says:

    Hello friends –

    The second reference I bothered to check was the same thing.

    From Whitaker:

    At the end of 14 months, core ADHD symptoms were reduced more in the children treated with stimulants than with behavioral therapy. However, at the end of three years, “medication use was a significant marker not of beneficial outcome, but of deterioration. That is, participants using medication in the 24-to-36 month period actually showed increased symptomatology during that interval relative to those not taking medication.”

    Technically true, but he’s leaving out this part from the paper:

    As one mightmay exped if
    selection effects were operative, Comb and MedMgt
    subjects who discontinued medication during the24 to
    36-month period had been doing well at 24 months
    (improvement from baseline of >0.9 on the 0-3 item
    mean of ADHD symptoms) and continued to improve
    through 36 months, whereas Beh/CC subjects who
    began high medication use during the 24- to 36-month
    period had not been doing as well at 24 months
    (improvement of only 0.6 from baseline) but then
    improved slightly after starting or increasing medication
    use. These findings highlight the likelihood of self selection factors among subjectsin their 24 36
    month medication use, in which increases or decreases
    in medication use may be the result rather than the
    cause of 36-month symptom levels

    This isn’t an example of quality documentation, but rather, expediency towards a conclusion at the expense of other potentially salient information. That’s a tough nut to swallow, because I am terrified about kids getting medicated like this, but this isn’t the type of analysis we should be using to show harm, it’s the flip side of the shoddy analysis used to sell the drugs in the first place.

    Boo.

    - pD

  22. cervantes says:

    Well okay pD, but that’s actually saying the drug are probably useless at improving school achievement or treating hyperactivity — and they have very serious side effects. So I wouldn’t say the data contradicts his points at all, even if he may have spun it a bit in the annotated bibliography. The authors of the paper are applying major spin by trying to claim “a uniquely beneficial effect on math achievement,” which seems highly implausible.

    Given the findings in that paper, I would never allow those drugs to be given to my child, that’s for sure.

  23. WilliamLawrenceUtridge says:

    One issue which has me raising an eyebrow is the apparent unspoken assumption that all medications will result in chronic (i.e. lifelong) use. It’s quite possible some people will need the medication for life (the severely depressed, for whom there is the best evidence of a need) while others may use the medication once faced with a particularly difficult time that goes above and beyond the ordinary pains of living.

    Of course, I could simply have to read a bit closer.

    Interesting comments for the most part though. It’s pretty obvious that this is an area of huge debate, which isn’t surprising considering we’re messing with the very organ we use to understand what we’re messing with, and more than most other organ systems studied in medicine, there’s a tremendous degree of adaptability and potential for self-modulation. I hope they can preserve my brain in a jar after my body dies, so I can keep up on this stuff : )

  24. Geoff says:

    @Scott

    That was a lede in a four paragraph comment. Anecdotes are sufficient to make a lede.

  25. Scott says:

    @ Geoff:

    Not when the other three are entirely evidence-free.

  26. JJ from Cowtown says:

    Correcting Geoff’s post…

    “Having seen many individuals reverse minor to relatively severe levels of depression and other mental illness through any intervention, I feel pretty confident that it is necessary to perform well-constructed studies to separate the truly effective interventions from the ones that simply appear effective.”

    Restated in the words of Dr Crislip: The three most frightening words in medicine are “in my experience.”

  27. Geoff says:

    @JJ from Cowtown

    We do know that biochemistry plays a role in a number of mental disorders. We know that SAD for example, can be treated with sunlight. We know that tryptophan deficient diets lead to diminished levels of serotonin.

    I am taking it one step further, and saying that any chronic sadness is a symptom of biochemistry problems in the brain. I am saying this because if it’s not biochemistry, then what is it? The only alternative that I see is life events, but again, I find it highly suspect to suggest that tragedy can cause chronic sadness, for a number of reasons.

    The most important is evolutionary plausibility. It is well established that wild homo sapiens experienced an inordinate amount of tragedy/death in their lives. 20+% of children not making it to the age of 5, lives being cut short by predators, dehydration, starvation, infections that they cannot cure, etc. But I find it hard to imagine that these events would cause chronic sadness, because if it did, it would be a massive survival disadvantage, and would get quickly filtered out of the gene pool. This is actually backed up by more recent anthropological data. Many an anthropologist has been shocked by the level of happiness among healthy hunter gatherer tribes given the amount of tragedy they experienced.

    And yes, another reason why I favor biochemistry as an explanation is because I have seen people anecdotally reverse various forms of depression. But the brain is an emergent system, and so I don’t necessarily think that drug treatments are a smart way of tackling these biochemical issues. It’s far too reductionist, and it treats the symptoms, not the causes. In my opinion, the causes are diet, lack of sleep and lack of sunlight.

  28. Rob Tarzwell says:

    I’ve never been terribly impressed by arguments of the form, “There is a demonstrable brain lesion, therefore X is a Real Disorder (TM)!”

    If I see someone who has been on the couch at home crying for a week and wishing for death, I see someone in trouble who has come for help, and the hunt for a lesion is a bit beside the point, once I’ve ruled out the important must-never-miss stuff.

    I don’t care whether you call it a “disease” or a “disorder” or a “problem in living.” For anyone who cares to do a bit of reading in the philosophy of psychiatry literature, there are actually some very skilled efforts at analyzing those concepts. Szasz and Laing somehow still get trotted out, 50 years later, as though they are *still* les enfants terribles of psychiatry. What they said was important, and at the time urgent, but the critics have replied, decisively in my view.

    Harriet does state above a big reason for the medicalization of misbehaving children: money. The American social safety net has been thrown on the fire to a large degree. A desperate single mother with an out of control child needs the help of a no-longer-extant extended family. Failing that, she could turn to social services, but oops, they’ve gone away too. Who’s left holding the bag? Some poor schmuck psychiatrist who sees the desperation in her eyes, sees the problem for what it really is, but also knows that if he calls the kid, “ADHD,” she’s going to get some desperately needed grocery and childcare money, maybe some expanded Medicaid services too. And voila!

    This is hardly an evil conspiracy or a complacent and smug field. It is simply making the best of a bad situation in the face of an enormously changed social, cultural, and political landscape over the past 5 decades.

    I’m not exactly sure what Angell’s beef with psychiatry is, but it smells a bit too “J’accuse!” to me. I doubt she’s ever spent a day in an inner city mental health clinic, where most of the medicalization of kids is happening.

    As for Whittaker, I really like Bob Whittaker, I enjoyed reading “Mad in America,” and I’ve even corresponded with him from time to time. However, and I’m sure he’d agree, he’s not immune to critique. He points to early 60′s proclamations by the NIH about the natural history of depression, showing it as a self-limited, one-time problem.

    Well, the problem here is, frankly, in the 60′s, we sucked at psychiatric epidemiology. We’ve got a lot better, and it just does seem to be the case that a significant subset of depression sufferers really do experience recurrences. And yes, there are large enough groups of them who have never been treated to form meaningful comparisons. I commend to you the Epidemiological Catchment Area study (ECA), the National Comorbidity Survey (NCS), and the NCS-R (Repeat).

  29. Rob Tarzwell says:

    NCS-R is *Replication* not Repeat. Apologies.

  30. nybgrus says:

    @Geoff:

    As someone who holds a degree in medical anthropology, who graduated with high honors in the field, I can tell you that using anthropological ideas and evolutionary stories to justify plausability is going to be wrong vastly more than it will be right. Most of anthropology, particularly medican and evolutionary, is rife with “just-so” stories based on loose strings on evidence, framed in extreme cultural relatively (hence your “happy natives” comment), and steeped in the skills and tradition of the raconteur. While they may generate the correct story from time to time, not only is that going to be a very small portion of the time but it is impossible to tell when that is. If understood from the point of view of best guesses at a good story, then it is a fine (if lacking in rigor) field. But taking it to offer plausability for scientific statements is simply bound to fail (and spectaculalry so, as we have seen time and time again).

    Furthermore, this concept of “we evolved 30,000 years ago” and therefore whatever diet, selection criteria, etc were in existence at that time is still the most valid model for us today (like the paleo diet, for example) is total garbage. We have evolved quite a bit since then and are still evolving today. Gene pressures and selection for traits still exist and can change over relatively small time frames, just like any other evolutionary process. Even more so, since most of the things discussed re: this topic specifically are pleiotropic and complex in phenotype and involve the modeling, remodeling, and plasticity of the brain. Brain development is not done for years after birth, so changes in sociocultural context can have profound influence independent of gene variance. So not only is it too simple to say “The most important is evolutionary plausibility. It is well established that wild homo sapiens experienced an inordinate amount of tragedy/death in their lives. 20+% of children not making it to the age of 5, lives being cut short by predators, dehydration, starvation, infections that they cannot cure, etc. But I find it hard to imagine that these events would cause chronic sadness, because if it did, it would be a massive survival disadvantage, and would get quickly filtered out of the gene pool” but it is also very wrong to assume that just because 300 years ago that would have been the case, it still must be the case because of some sort of stagnation in evolution at that point in time.

  31. nybgrus says:

    wow, I re-read my comment and there are many a typo…. should still be understandable, I reckon.

  32. qetzal says:

    @Geoff,

    This issue is not whether biochemistry plays a role in mental disorders. At some level, biochemistry MUST play a role in any disorder, mental or otherwise.

    The objection is to your claim that:

    Having seen many individuals reverse minor to relatively severe levels of depression and other mental illness through dietary intervention, so I feel pretty confident that it is a chemical imbalance.

    I’ll happily accept your word that you’ve seen individuals recover from depression after dietary intervention. That by no means shows that they recovered through dietary intervention. That’s especially true for a condition like depression, that tends to resolve over time in lots of people, regardless of intervention.

  33. Rick says:

    Thank you for reviewing this. I read Dr. Angell’s articles with much interest and posted some excerpts in comments on SBM. It appears this will continue to be a grey area to do the subjective nature on how many mental illnesses are reported, presented and diagnosed since there is not an objective lab or radiological study to aid the clinician. To me, this is the kind of issue that SBM should be weighing in more often. Would be great if one of you was posting on Scientific American since they seem to be debating things that are a little more grey like pro-biotics. I think most of us that have been reading SBM for a while know most of the pitfall of the anit-vaccine movement and sCAM. While, keeping up-to-date with the on goings of those anti-science folks perhaps on a monthly or quarterly basis, I am much more interested on SBM’s thoughts on other areas.

  34. WilliamLawrenceUtridge says:

    You can’t compare hunter-gatherer societies with modern on a lot of things. The diet, exercise, social structure, belief systems and so much more are too different. Further, as Robert Edgerton’s Sick Societies points out – hunter-gatherer societies are not near so idyllic as many myths have presented them. There’s more violence, less food, more anxiety, less medicine, and far, far less diversity. You have a role, you occupy it. You’re plagued by spirits, hounded by ghosts, bound by taboos, and in modern times you are probably being forced to change. As for the “savages suffer less/more than us” argument – I don’t think it’s even comparable. You live in a tightly-knit community where death is common. You believe your ancestors live after their death and you communicate with them directly and indirectly. The entire landscape is enchanted (is that the word? I think there’s a specific anthropological term that’s used to describe the way supernatural etiologies are projected onto the landscape). It’s such a different life that any comparison would seem to fail and any justification based on “well, hunter-gatherers do it” seems rather absurd. The life of a hunter-gatherer is hard, civilization is essentially an effort to get away from it, and with substantial justification.

  35. daedalus2u says:

    Geoff, that facile analysis that “If “chronic sadness” could occur in a healthy brain, it would have been selected against.” holds for every chronic illness. As you point out, there are many circumstances where acute events do cause acute sadness in healthy brains. Is chronic sadness the equivalent to acute sadness that has not been compensated for by the acute sadness compensatory pathways?

    Healthy brains have to be able to instantiate both joy and sadness so as to be able to regulate mood and compel organisms to do activities that produce joy and avoid activities that produce sadness. From that perspective, chronic sadness derives from a problem with the control pathways that turn off the sadness producing signaling pathways and turn on the joy producing pathways.

    There are environmental triggers that can differentially produce these different moods (birth of a child, death of a child, recovery of a child) those moods must be mediated through differential signaling pathways in the nervous system. A “chemical imbalance” that skews the signaling pathways to increase the ability of an environmental trigger to cause sadness and decrease the ability of an environmental trigger to reverse that sadness would increase the incidence of sadness in the population.

    Because the triggering of mood changes by environmental signals is already ongoing, any skewing of those changes would have an effect, with no threshold, even if the change might be too small to measure and might only be apparent over large populations.

    Nitric oxide is involved in the signaling pathways that regulate mood, but that signaling is complicated. Skewing the nitric oxide level would skew the mood regulatory pathways of the organism with the skewed nitric oxide status.

    Nitric oxide is involved in other physiological pathways too. It regulates blood flow (low NO means lower blood flow). It regulates energy status (low NO means lower ATP). It regulates steroid levels (lower NO means higher androgens). It regulates blood pressure (lower NO means higher blood pressure).

    As far as I can tell from the literature, if there is a “chemical imbalance” in depression, a reduction in nitric oxide status of a depressed individual is consistent with the symptoms and comorbidities of depression. Depression is a complicated state and requires the whole brain (and organism) to be in the depressed physiological state (which is why it affects the brain and the whole rest of physiology), but it is a state that organisms have evolved to be able to invoke when needed.

  36. Geoff says:

    @daedalus2u

    I agree. In my opinion, every chronic illness, with the exception of a select few genetic mutations, is preventable.

    I don’t necessarily think that acute sadness is equivalent to chronic sadness that hasn’t been compensated for. In fact, I suspect that in most cases, it is the opposite. The brain chemistry makes someone sad, then they find something to be sad about.

    I don’t understand this nitric oxide theory. Not to say that it’s wrong, but I would be interested to learn a little more about it. At this point, nitric oxide does not factor into my understanding of nutrition or disease at all.

    @nybgrus

    I now know that that is your opinion, but you are wrong. Just because something is outside of our evolutionary experience doesn’t mean that it is harmful, but the fact that something is in our evolutionary experience does mean that it is almost definitely not, at least at normal levels obtained by whole food sources.

    With the science not in, it is a respectable position to take, however, in this case, you happen to be wrong. Still, I’m not saying that we should just guess, I am saying that we need to use an evolutionary framework to evaluate the evidence. So you do a bunch of studies with a bunch of different conditions, and they all tell you different things. The thing that unifies them is that they are all biology, and thus results of our evolutionary history.

    @WilliamLawrenceUtridge

    I’m not talking about a reenactment. When we put animals in a zoo, we feed them food that is appropriate for their evolutionary metabolic millieu. When we don’t, they get sick. http://hunter-gatherer.com/blog/health-problems-disappear-when-captive-gorillas-fed-wild-diet

    Our pets get the same diseases that we have when we feed them inappropriate chow. They are healthiest on an evolutionarily appropriate diet as well: http://hunter-gatherer.com/blog/health-lessons-westminster-kennel-club-dog-show. Why wouldn’t this be true for humans as well?

  37. evilrobotxoxo says:

    A couple of comments:

    1) Angell has good credentials

    Yes, but credentials for what? There is no indication that Angell has received any specialized mental health training or clinical exposure beyond doing a psychiatry rotation in med school decades ago. I don’t think that means she has excellent credentials to criticize the entire field of psychiatry.

    2) off-label prescribing

    Angell identifies something that is, to some extent, a real problem. However, her proposed solution is counterproductive and intellectually inconsistent. It is counterproductive because it would discourage off-label use of cheaper, older medications because no company will pay for FDA indications for an off-patent drug. Essentially legislating psychiatry into the pocket of big pharma. It is intellectually inconsistent because Angell bashes the DSM, fairly to some extent, but then comes up with a plan to use DSM diagnoses, basically entries in a book of billing codes, to dictate treatment decisions. It makes no sense.

    3) “chemical imbalance”

    This is a straw man argument, pure and simple. No one in psychiatry really believes things are that simple. As has been pointed out here, there is a subtle underlying notion that because the pathophysiological mechanisms of mental illness are not known and readily detectable using objective tests in the clinical setting, that these actually don’t exist. One thing that critics of psychiatry ignore is that most psychiatric disorders actually have differences that can be detected with neuroimaging, in autopsy studies, etc. However, the problem is that none of these tests are sensitive or specific enough to be useful in the clinical setting. That doesn’t mean the objective findings are not real. It’s also worth noting that for many conditions, studies have shown that imaging groups of patients before and after treatment (either pharmacological or psychotherapeutic) changes their brain activity to be more “normal” than before.

    4) psychiatric evaluation

    Carlat’s notion that psychiatrists simply ask about symptoms then match them up to the DSM is flat out absurd. A lot more goes into it than that. If Carlat really does practice psychiatry that way, it’s a little frightening.

    5) psychoactive drugs as placebos

    This is one point where I have to criticize Dr. Hall’s article. Anti-psychiatry zealots try to paint all psychoactive medications with the same brush, suggesting that because antidepressants have modest efficacy in breaking a major depressive episode, that means that all psychotropics barely beat placebo. Unfortunately, Dr. Hall falls into this trap. The reality is that there are a number of classes of psychiatric meds that have nothing to do with antidepressants and have significant proven efficacy beyond that of antidepressants; these include antipsychotics for schizophrenia or bipolar, mood stabilizers for bipolar, stimulants for ADHD, or benzos for anxiety, among others. You can also include in that other uses of antidepressants, including for OCD, PTSD, GAD, panic disorder, etc., as well as in preventing relapse of depression, which is where the data supporting antidepressant efficacy is the strongest.

    6) number of diagnoses in the DSM increasing

    The fact that the DSM includes more and more diagnoses does not mean that more and more people meet criteria for a mental illness. It is basically an effort to end the tyranny of the “NOS,” or not otherwise specified. Basically, lots of patients come in with severe symptoms in a certain cluster, such as anxiety, but they don’t fall into any of the predetermined DSM categories. So those patients get a diagnosis of anxiety disorder NOS. The DSM keeps adding more and more diagnoses, but it’s adding more and more subtypes of each of the main symptom clusters, not redefining the symptom clusters to include more and more people. Whether this is worth doing is highly debatable, but the goal is to characterize patients more precisely, not to label more and more people as mentally ill.

  38. daedalus2u says:

    Geoff, I agree that depression is not like chronic sadness. However both are whole-organism physiological state and so must be a product of the regulation of the physiology of the whole-organism. There must be physiological pathways that produce acute sadness and also depression. The persistence of acute sadness into chronic sadness and the persistence of chronic depression must be from the lack of physiology that switches the psychological state out of the chronic sadness or chronic depression state. This is not a hypothesis, it is a tautological statement. If anything persists, it only persists because there is the absence of something that makes it not persist. We observe that individuals can come out of a physiological state of chronic sadness and chronic depression, that means there is physiology that can cause those physiological states to change.

    I think that trying to focus on the physiology of the “cause” is less helpful than trying to focus on what changes can be made to physiology to get the individual out of the bad physiological state that is causing the problem to persist.

    A starting point for the role of NO in physiology and how it may couple to conditions of modern life is here.

    http://books.google.com/books?id=a3mwmXzpsjkC&lpg=PP1&pg=PA103#v=onepage&q&f=false

    This outlines a hypothesis of how modern living has changed a fundamental physiological attribute of humans which may have skewed physiology to a lower NO/NOx state. Skewing NO/NOx to a lower level will skew all physiological signaling pathways that utilize NO as a signaling molecule to the state characteristic of the normal physiological states that are low in NO, these including the acute stress states.

    This write-up is focused on the immune system, but there is NO/NOx involvement in every other physiological system too.

  39. Harriet Hall says:

    @evilrobotxoxo,

    “Yes, but credentials for what?”

    Credentials for critical thinking about medical issues.

    “there are a number of classes of psychiatric meds that have nothing to do with antidepressants and have significant proven efficacy beyond that of antidepressants;”

    I did not mean to say that other psychoactive drugs are not effective. Sorry if the way I worded it gave that impression.

  40. Harriet Hall says:

    @Geoff,

    “With the science not in, it is a respectable position to take, however, in this case, you happen to be wrong.”

    Since the science is not in, how can you presume to tell him he is wrong? If you can presume, so can I: You are wrong.

    “Our pets get the same diseases that we have when we feed them inappropriate chow. They are healthiest on an evolutionarily appropriate diet”

    References, please. From scientific studies, not from a blog promoting an ideology.

    “every chronic illness, with the exception of a select few genetic mutations, is preventable.”

    Demonstrably not true. Just one example: cancers caused by DNA copying errors.

    Do you think that people following your diet recommendations will never develop chronic illnesses? A study could easily be done, and I think you might be very disappointed with the results. If they did develop chronic illnesses, would that make you give up your beliefs?

  41. WilliamLawrenceUtridge says:

    I’m not talking about a reenactment. When we put animals in a zoo, we feed them food that is appropriate for their evolutionary metabolic millieu. When we don’t, they get sick. http://hunter-gatherer.com/blog/health-problems-disappear-when-captive-gorillas-fed-wild-diet

    Our pets get the same diseases that we have when we feed them inappropriate chow. They are healthiest on an evolutionarily appropriate diet as well: http://hunter-gatherer.com/blog/health-lessons-westminster-kennel-club-dog-show. Why wouldn’t this be true for humans as well?

    Many animals are strongly adapted to a specific food source, and the diets of fossilised animals can be identified by their teeth for this very reason. As such, comparability is going to be fairly limited. Humans are omnivores able to adapt to an almost fully-vegan diet (Jains, though they need the bacteria found in unprocessed water to get the necessary B12) and an almost fully meat-based diet (Inuit in northern Canada) and thrive. Dogs are carnivores, and have a completely different digestive tract. You can’t feed a tiger leaves and you can’t feed a cow meat (or rather, you can and they suffer for it) and a panda must eat bamboo. Humans don’t have that. You’re a bit closer when you discuss gorillas, at least they are in the same family as humans. But still, human diet has experienced selective pressure as well – lactose tolerance for instance, is an evolved trait.

    The “healthiest” diet is something very much up for debate. Feeding pets raw food can give them diseases that they don’t get when eating processed food. I’m extremely skeptical when anyone claims there is a single, magic diet that answers all health questions. I also don’t think that there’s a single magic diet that is responsible for, or cures, mental health. Particularly given the vast diversity of the 6 billion people on this planet. Signal emerges from noise when studied, I’ve yet to see any dietary recommendations that are universally accepted by all groups beyond “don’t eat too much of one thing and exercise”.

    But perhaps I’m wrong, and if there is such a magic diet, it should be demonstrable.

  42. evilrobotxoxo says:

    @Dr. Hall

    “Credentials for critical thinking about medical issues.”

    Critical thinking is necessary but not sufficient. As Dr. Angell demonstrates, sometimes actual knowledge of what one is thinking critically about is required.

    “I did not mean to say that other psychoactive drugs are not effective. Sorry if the way I worded it gave that impression.”

    No problem. However, I do think it is something to be careful of. Attacking the entire practice and concept of psychopharmacology because antidepressants don’t work well for one specific indication is like attacking evolution because something’s missing from the fossil record of a fish in China.

  43. DW says:

    Geoff:
    “In my opinion, every chronic illness, with the exception of a select few genetic mutations, is preventable.”

    “I don’t necessarily think that acute sadness is equivalent to chronic sadness that hasn’t been compensated for. In fact, I suspect that in most cases, it is the opposite. The brain chemistry makes someone sad, then they find something to be sad about.”

    Both of these statements seem preposterous. The first is pie in the sky; the second, well, must we assume that nothing has ever happened in your life that made you sad?

    So if my dog gets run over by a car and I’m sad, really my brain chemistry just happened to change negatively right at the same time, by coincidence, and I’m just using the death of my dog as an excuse to be sad? If I changed my diet, I wouldn’t be sad if my dog is killed?

  44. Geoff says:

    @Harriet

    Cancerous cells caused by copying errors get killed via apoptosis in healthy individuals. They occur multiple times in everyone every day.

    If a study was designed correctly, and subjects in the study developed chronic illness, then yes, I would reevaluate my beliefs, absolutely. Because this is an evidence based conviction, not a faith based belief. Still, I think that you would be shocked by the results of such a study. Even if we just did a 30 day intervention study on people with autoimmune diseases, you would be shocked. The reversal of the disease process in RA, MS, lupus, scleroderma, myocitis, Crohns, UC, Huntingtons,

    A properly designed 30 day paleo intervention can cause astronomical changes to every biomarker of health you can imagine. CRP from 7 –> 0.9, TG from 200 –> 45, TC from 400 –> 200, HDL from 35 –> 65, LDL particle size from B –> A, weight loss > 20 lbs while increasing lean mass, hair loss halted, depression gone, acne gone, eczema gone.

  45. Geoff says:

    @daedalus2u

    I don’t find this hypothesis particularly compelling. It doesn’t explain any of the following:
    1. Why does obesity go down as income goes up in the US? Wouldn’t the hygiene hypothesis predict the opposite?
    2. Why is obesity extremely high in third world countries like Trinidad?
    3. Why does a tasteless liquid diet reset the fat mass setpoint?
    4. Why do rats fatten on chocolate ensure but not vanilla or strawberry?

    I will admit that I do not use shampoo or soap when I shower, and haven’t for about a year now. But this is more about oil production in the skin than it is about bacteria. I still shower every day, and I still wash my hands with soap after every bathroom use and before cooking.

    I do think that exposing children to a wide range of bacteria from a young age will be beneficial to them in the long run, because I do suspect that parasites play a significant role in many disease processes. But for a full grown adult, I have not seen any evidence that bacteria on the skin improves health, and I suspect that reducing bacteria exposure as much as possible is going to minimize health risks.

  46. Harriet Hall says:

    @ Geoff,

    “Cancerous cells caused by copying errors get killed via apoptosis in healthy individuals.” Some of them do, but some result in cancers that are probably not preventable. See
    http://www.sciencebasedmedicine.org/index.php/a-new-perspective-on-the-war-against-cancer/

    “A properly designed 30 day paleo intervention can cause astronomical changes to every biomarker of health you can imagine. CRP from 7 –> 0.9, TG from 200 –> 45, TC from 400 –> 200, HDL from 35 –> 65, LDL particle size from B –> A, weight loss > 20 lbs while increasing lean mass, hair loss halted, depression gone, acne gone, eczema gone.”

    Citations, please!
    Did any studies compare the results of a paleo diet to other diets resulting in comparable weight loss?

  47. Rob Tarzwell says:

    @evil, well said again, ma’am/sir. I had never really stopped to think more carefully about diagnostic proliferation within the DSM, but your explanation seems quite apt. I’m generally stuck with the NOS label between 1/4 and 1/3 of the time.

    I think, however, the ultimate solution to specificity won’t be expanding the specific syndromes, though this has been an important road to go down in the evolution of psychiatric nosology. Analysts don’t get much credence today, but one thing I really like about the analytic project was its effort to link highly variable surface phenomena with elegant depth explanations. It attempted to ground function, dysfunction, and symptomatology within a complete theoretical framework.

    I’ll extend your cardiac metaphor a bit. Psychiatry, lacking a fundamental theory, is much like internal medicine a century ago. The patient has chest pain. This one has crushing retrosternal chest pain which radiates into the jaw and left arm. That one has epigastric burning. A third one has lancinating pains with deep breathing. So, we create a diagnosis of Angina, and then we subtype it by its different clinical manifestations. Only with the slow march of pathology do we discover cardiac ischemia, esophagitis, and pleuritis.

    In psychiatry, we’re still very much in the bird-spotting phase of the science. Our Darwin hasn’t come along yet to help us put all these species on one grand tree. So, in the meantime, because we’re looking for birds, we keep finding new variations on birds. But, what’s a species and what’s simply variation within a species is simply unknown.

    It seems a truism to say the answers will come from functional neuroscience. What those answers ultimately look like will be complex, surprising, and we ultimately have to abandon any meaningful pursuit of a unifying theory. I hope not, but it may come to that.

  48. vicki says:

    Geoff–What you’re overlooking is that autoimmune disorders tend to fluctuate in severity over time. If I designed a study in which I gave patients with MS and RA a vegetarian diet heavy in chocolate and brown rice when they were having bad symptoms, and then put them on a paleo diet when they were feeling their best, I suspect I could “show” that the paleo diet caused exacerbations and flare-ups, with about as good reliability as your claim of the reverse. It’s called regression to the mean.

    That said, if you really have evidence of a cure for MS, you shouldn’t be talking to us, you should be talking to the National MS Society. (But don’t buy your ticket to Sweden just yet.)

  49. libby says:

    I solved my depression issues in the following way.

    I first assessed the function of the depression, in my view the flip side of anger, realizing it has a function.

    If you have low self-esteem, it allows you to feel comfortable with this distorted self-view. The muttered phrase, “I don’t give a shit” is mollifying, allowing you to avoid all sorts of issues brewing within the unconscious. So it functions partly as a tool of avoidance.

    But it also functions as a problem solver.

    Once I discovered this, I realized that my unconscious, the seat of such pseudo problem-solving, is very bad at actually solving any issue it thinks needs attention.

    This ‘problem-solving’ can take extreme measures, such as in the Colombine massacre. To the participants, it did solve a number of issues; revenge against the teachers and other students, and altering their life path, permanently. It was quite an effective solution, albeit undesirable.

    I noticed a chemical component to depression, feeling depressed without cause. I could also feel quite content after taking a pharma drug for moderate pain, again without cause.

    So I concluded that instead of handing over to the unconscious any problem-solving duties, I would identify the real problem, and then consciously deal with them. If I noticed any chemical nose-dive, I again identified it, and then ignored it for what it was.

    None of this admittedly has any scientific basis, but it is how I successfully dealt with depression. It’s quite easy once you find out how to re-frame your belief system.

    Perhaps what is needed in mild cases is that people are given, or better, discover for themselves, tools to deal with the issue.

    It would be interesting to discover how effective such an idea would be for more severe conditions.

  50. woo-fu says:

    @HH–I thought this was a fair analysis. Anti-psych groups generally allege that psychiatry/standard medicine is reluctant to critically examine its own practices; however, you consistently provide evidence to the contrary. Thank you.

    @WLU–re: the one “best” diet BS–I completely agree. It may be cliche, but “one person’s cure is another person’s poison” still seems pragmatic.

    @nybgrus–There was an illustrated book some time ago (70s?) highlighting the subjectivity and biased assumptions in the field of archeology. The implied objections are very similar to your assessment of bias and error in your field of training. I wish I could remember the title; it may have even been a feature of a magazine.

    Set in the future, the archaeologists are excavating a dwelling with the name of something like Toot & Come in! (yep–bad sound pun there) which is actually an old abandoned motel. Based on the arrangement of furniture, they determined the people of this settlement must have worshiped at their main altar (TV & stand) and proposed many other unconventional uses for everyday hotel items. It was much funnier than my explanation, and the illustrations were fantastic.

    If anyone can find it or figure out the true title–it’s really worth a read. And you can even use it to teach fallacies to the young’uns!

  51. Geoff says:

    @Harriet

    I’m sorry, that was an opinion. Those are specific anecdotal examples that I have seen, there is no citation.

    I do doubt that there are cancers that are not preventable. However, I will concede that there MAY be cancers that are not. If there are, they should be as a result of a genetic mutation, and the frequency should be on the order of what the math would predict for such a mutation. However, the vast majority of cancers that we see in the modern world; epithelial cancers, particularly in endocrine organs; are preventable. In my opinion, of course.

    Also, I think that sleep duration and quality play a significant role in cancer, so if I were going to be serious about designing a study or a health intervention for an individual, I would certainly control this variable as well if I can, and to the extent which I cannot I would at least measure it so that I can correct for it.

    @Vicki

    I am aware, I had/have systemic scleroderma, and over the course of about 6 months my disease process stopped as a result of a very high dose methotrexate intervention along with cyclosporine. Or was it the 50 lbs of weight loss due to feeling sick and being incapable of eating much? The world will never know. This was when I was 16.

    As an aside, I have never heard of calorie intake or weight loss being corrected for in any chemotherapy drug study, but anecdotally the sicker a drug makes you the better it seems to do. Not saying that chemotherapy doesn’t work, but I am saying that IF a ketogenic diet does, then we should probably start paying attention to weight loss because weight loss is calories from animal (your) fat replacing other foods in the diet. In my opinion, ketogenic diets are effective in treating many if not most forms of cancer, and the effectiveness of chemotherapy drugs is overstated because weight loss is not corrected for.

    Cordain does sell an MS product: http://thepaleodiet.com/store/ms-products/. There’s a video somewhere on the web of a Cordain presentation where he discusses the proposed mechanism by which MS could be caused by wheat. From memory, this involves WGA getting into the bloodstream undigested, binding to a sugar molecule at a time when the body is fighting an infection, and causing the immune system to produce a specific antibody to this molecule that accidentally attacks myelin. I believe this is known as molecular mimicry. If this mechanism is right, or even if it’s wrong but molecular mimicry is the cause of MS, then removing the foods that are causing the body is releasing the antibodies in response to would reverse the disease process. That dose not mean that permanent damage isn’t still permanent, obviously.

    I’m not a huge Cordain fan, though I owe a lot to him. I call myself “paleo 2.0″ because I think that there are a lot of ideas in the “paleo 1.0″ community that are wrong and not validated by the science. For example, I don’t think that there is good evidence that tabula rasa, any grain other than wheat is problematic. Same can be said for dairy, which is a considered a “non-paleo” food. The paleo 2.0 neolithic agents of disease are wheat, excess linoleic acid and excess fructose. That’s not to say that for someone who is unhealthy, avoiding all grains isn’t required to heal, though.

  52. Harriet Hall says:

    @woo-fu,

    The book is “Motel of the Mysteries” by David Macauley. It’s a hoot!

  53. Harriet Hall says:

    @Geoff,

    Your understanding of cancer is sadly defective. Please read “The Emperor of All Maladies” for an accessible and eloquent presentation by a cancer expert.

  54. nybgrus says:

    @Geoff:

    I now know that that is your opinion, but you are wrong.

    It’s not just my opinion, I have entire degrees in the relevant fields. It is my well informed opinion, based on years of study and understanding of all the relevant background science (and anthropology).

    When you offer an opinion, as you just admitted – that is all it is a pure opinion. The mistake you make is then assuming that the science will bear you out until you actually do the science. You must first assume you don’t know and fall back on what we do know. And what we do know so far does not support your claims.

    You also make an extremely grave mistake:

    Our pets get the same diseases that we have when we feed them inappropriate chow. They are healthiest on an evolutionarily appropriate diet

    No, you are not feeding them “an evolutionarily appropriate diet.” You are feeding them the diet that is currently best for them based on their current evolutionary state. Unless you are going to tell me that feeding your cat live lizards and mice would be best for them… and then I would tell you that you are wrong again. The cats and dogs that are the healthiest and win those shows and have the best teeth and coats etc are not fed anything remotely resembling what they would get in the wild today, let alone XXX thousands of years ago.

    You are further mistaken in the next claim:

    Cancerous cells caused by copying errors get killed via apoptosis in healthy individuals

    Until they don’t. That is how cancer goes. It is an absolute fallacy to think that cancer cells arise constantly and are killed without fail until our health or nutrition dips and we miss one. It is just a numbers game until enough mutations arise to make a robust stem cell and then it won’t matter how healthy you are. There are myriad factors that go into oncogenesis, including evasion of the immune system. The immune system applies selective pressure on the pre-cancerous cells and often the phenotype emerges that can succesfully evade a normal immune system. Oncology is an extremely complex field, so I can assure you that being on a healthy diet and otherwise being tip-top could help a bit, but will certainly not prevent cancer from occuring.

    You go on to say:

    However, I will concede that there MAY be cancers that are not. If there are, they should be as a result of a genetic mutation, and the frequency should be on the order of what the math would predict for such a mutation. However, the vast majority of cancers that we see in the modern world; epithelial cancers, particularly in endocrine organs; are preventable. In my opinion, of course.

    Based on what? Your opinion is literally just a random guess. You don’t even seem to understand the basis of oncgenesis – all cancer is the result of genetic mutations. Every last one. They have different mutations that are specific to each cancer type, some are in germ line cells and passed down, most are sporadic and random. Cancer doesn’t happen because you get sick. Cancer happens because the correct combination of mutations manage to arise in a cell. Over 50% of cancers evolve a mutation in the p53 gene which allows for the cell to divide even if the DNA isn’t copied right. Other mutations involve growth factor receptors. Others still angiogenic factors. Expression of collegenase. The list goes on and on. And on top of that, each cancer has myriad subtypes based on which set of mutations it got. That’s why you have ER/PR/Her2Neu typing for breast cancer – and we are learning it gets even more refined than that. And to top that all off, cancer cells actively evolve. Drug susceptibility changes as the cancer is exposed to it. It can express the MDR gene and pump out chemo agents. It can downregulate expression of one growth factor receptor and change it for another. Your understanding of cancer is very limited and it shows in your simplistic explanation of your opinion on preventability of cancers.

    You must also realize that there is a distinct difference between reducing known risk factors and preventing cancer. We know, for example, that UV light will predispose you for melanoma. So reducing sun exposure will reduce melanoma – but it wont prevent melanoma. This is a vital distinction to understand. You are taking the higher incidence of cancers and assuming that if you remove the risk factors and lead a healthy diet that will prevent the cancers from occuring in the first place. The only thing it will do is reduce the incidence down to background levels – which are not zero.

    And before you go on and say “Well, I am sure a study would vindicate me, and if it didn’t then I would change my mind.” That is bad science – you don’t assume the conclusion until proven otherwise. Moreso, it is bad science because it simply doesn’t jive with what we actually do know. That is not to say that it is most certainly wrong – you could, in theory, be correct. But the way you frame your arguments, come from opinion that is not in line with the body of evidence nor our understanding of oncogenesis, and then assume the conclusion until a study of your liking proves you wrong is simply flat out bad science.

    Lastly, before I go too off the rails here:

    In my opinion, ketogenic diets are effective in treating many if not most forms of cancer, and the effectiveness of chemotherapy drugs is overstated because weight loss is not corrected for.

    We have had this discussion before Geoff. Dr. Hall and myself both gave you extensive reasons why your conclusions were unwarranted and why it was bad science to think the way you were about it. You seem to continue to ignore that. And you never managed to address the points raised to you – you just love touting “your opinion.” I don’t know what else to say except that your opinion is flat out wrong.

  55. nybgrus says:

    @ woo-fu: Yes, I have read that book. It was an excellent one indeed – thanks for remembering the title Dr. Hall. Another good one is an article called Body Ritual of the Nacirema which also demonstrates this sort of thing.

    Honestly I feel a bit gypped in my anthro degree – the only positive is I learned the tactics, word choices (“secret” code), and just how garbage it is from the inside out. I actually really believed in what I was being taught – and there is some truth to it. But it is taken to such an extreme that it is really mind boggling. The funny thing is anthropologists will read the Nacirema article or the Motel of Mysteries and laugh, thinking they don’t do the exact same thing. At least when I bash anthro and “just-so” stories and people say to me (which they have), “Don’t bash it if you don’t know about it” I can whip out my diploma with a fancy golden seal of High Honors on it. BTW, have you noticed how people will freely comment on things completely outside of their expertise with confidence, but when someone points out their ideas are wrong the response is often “You don’t know the details of my particular woo.”

    I think people fail to realize that we also are indeed still evolving as a species. Michio Kaku (whose books I love to read) made a bloody fool of himself when he came on and started talking biology and declared that humans are no longer evolving. He is a brilliant theoretical physicist, but that does not mean he knows dork about biology. But, as people are prone to do, he felt that his expertise in one field translated to another. Geoff, let that be an example to you, please.

  56. WilliamLawrenceUtridge says:

    Seconding Dr. Hall’s recommendation of The Emperor of All Maladies, both as an overall recommendation (it’s an excellent, engrossing and highly readable book) and propos to this discussion. It has quite an interesting little summary of the evolutionary nature of cancer as well.

  57. daedalus2u says:

    Geoff, If you want to look at some actual data, WHO has a nice website with data on obesity and water & sanitation related deaths (a surrogate marker for developed world water supplies).

    http://apps.who.int/ghodata/?vid=2469#

    If you download the data and plot % BMI above 25 vs Water, sanitation and hygiene attributable deaths per 100,000 all of the high BMI nations have low water deaths. There are no high water deaths and high BMI nations. Many of the developed countries have death rates of 0 per 100,000. Many developed countries don’t even list deaths. Trinidad is 2 per 100,000, the US is 1 with BMI above 25 of 64.7 and 69.4 so Trinidad has pretty good water supplies and it isn’t surprising that it has a high BMI.

    Above 50 deaths per 100,000 there is no place with more than 50% with a BMI above 25. Above 75, there is no place with more than 40% above 25. Above 125 deaths per 100,000 there is no place above 30%. There are some populous countries with high death rates and low BMI, Nigeria is 129 and 28.8%. There are only small countries with low BMI and low water death rates. They may suffer from bad data gathering.

    Among the nations with low water deaths and low BMI, you have North Korea with 19 and 17.4, Indonesia with 20 and 20.7, the Philippines with 18 and 26.9, Thailand with 12 and 31.4, Vietnam with 7 and 10.1, China with 4 and 25, Sri Lanka with 4 and 21.7, Japan with 1 and 22.4, and Singpore with 0 and 28.1.

    There are some issues with using this data set, it can take ~10+ years for bathing to really start to affect BMI unless you have exposure in utero. Bathing practices in Japan are not like those in the west. Singapore has a lot of migration from China. In some places there is a large difference between the cities that have good water supplies and the countryside that doesn’t.

    I don’t understand the relevance of your other questions.

  58. Becky Murphy says:

    My comment may be “off topic” a little. I am just a mother, I am not a scientist, or a doctor. My son has a diagnosis of schizophrenia, which is supposed to be a diagnosis of exclusion. However, he received this diagnosis from the lead researcher for childhood schizophrenia in the State where we live, who at the time was one of the investigators participating in the NIMH TEOSS drug trials. My son had been given Risperdal at the age of eight to treat aggression, which he was taking when placed in this investigators care. This was an “off-label” use of the drug, for which J&J has been heavily fined, which is all well and good, but does absolutely nothing for the victims.

    Back to the diagnosis of exclusion: My son was aggressive due to having severe PTSD which was the result of having been the victim of violent crime. He was beat up and locked in a closet, and since this crime occurred while he was in State Care, it was covered up. Any conflict was perceived by him as a threat to his life, so it is understandable that he would fight for his life—he thought he was fighting for his life!

    The first psychiatric hospitalization occurred a month before his seventh birthday where an EEG discovered he had left temporal epilepsy. He also had an neuropsychiatric exam which determined he had an IQ of 146—my son was brilliant, an artist and had a verbal ability far beyond his years. He could do triple digit addition in his head and did not use his fingers to count. He put together 1,00 piece jigsaw puzzles by himself. He did these things all at the age of seven—before the neuroleptic drugs, were used.

    So when my son was thirteen, and this “doctor” and researcher told me he was diagnosing my son as having schizophrenia, I asked him about excluding the Left Temporal Epilepsy by having another EEG done he said it was not necessary, he just took the diagnosis off his record. he also said my son’s experiences with being traumatized were irrelevant.

    This psychiatrist, and in fact no psychiatrist who has ever treated my son, before this diagnosis or since; has ever had a realistic conversation with me about the effects of the psychiatric drugs that they prescribe my son. In fact the researcher told me I had no say in what drugs he was giving him; since I had been compelled by the State to make him a Ward of the State to get him treatment! This was a lie, since both State and Federal Law stated that my consent was in fact required—and really, this guy was basically using Washington State’s law giving 13 year old children the right to consent to mental health treatment. the law’s purpose was to enable children who do not have family support to get help they need, however it is used in this state to exclude parents. This opinion is not based only on my experience, but in talking to other parents over the last decade—it is obvious to me it is being used in this way by psychiatrists and other mental health professionals. But then, I have in my research found the push to lower the age of consent was funded by the pharmaceutical industry, so it is being used how it was intended, I suppose.

    My son is severely impaired and his cognitive and physical impairment began with the Risperdal prescribed at age eight which caused his eyes to have difficulty focusing. I understand now, after hundreds of hours reading and studying professional research about the drugs, this is and was a KNOWN, if not common effect. I also found a NIMH study which concluded that using neuroleptics to treat aggressive behavior in children was not advised. My son could no longer read and was given a label of being oppositional defiant because he said he could not do his schoolwork! I believed him, but no one else did. The psychiatrist at the time, failed to properly inform me about the known effects of the Risperdal–including the effect on prolactin production, or the effect of my son boy growing body hair and showing signs of puberty before his brother, who is five years older than he is; when he was nine!

    I agree that outlawing the “off-label” prescribing of drugs is not the solution; for the very reason this author states. The real issue is Informed Consent and the fact that Psychiatrists and other mental health professionals, who take their lead from these “doctors,” do not in fact think it is important. It is in fact the one thing that makes psychiatry unlike any other medical specialty, in my opinion. I had a psychiatrist tell me that no psychiatrist would see anything wrong with the “treatment” that was forced upon my son—against my protests and his own—by the federally funded research psychiatrist. He stated, “No psychiatrist would see anything wrong with the treatment. Any parent who protested, at best would be perceived as ill-informed, and at worst impaired themselves.”

    My son was given every one of the SGAs and molindone by the researcher. Ultimately he was put on Clozapine—my son will never be the same and he remembers his childhood as being “traumatized over and over and over” He in agony asked me, “How could they take so much from me mom?” I will probably spend the rest of my life taking care of my once brilliant son, who struggles to do the things he could in third grade.

    The issue as I see it, is there is a lawlessness in how psychiatry is being practiced in the real world; without ethics, without consent and without regard for the people it harms. Not even the Nuremberg Code is paid any heed.

  59. micwat says:

    Pardon my ignorance, but what is ‘off-label” prescribing? Am I right in thinking it means a physician prescribes a medication to treat conditions for which it has not been approved? How much latitude are doctors given for this? Is it required (either ethically or legally) that they have a reasonable science-based rationale for the prescription when they prescribe off-label?

  60. Diomedes says:

    Geoff has fallen into the classic trap of the adaptationist paradigm. That is, if humans have some trait, if it has “persisted” (of course, no data from Geoff on depression in paleo-humans), then it must have been selected for. As any practicing evolutionary scientist can tell you: that is bunk. Traits need not be continuously adaptive to persist. They can be selectively neutral, they can be adaptive only in certain circumstances in a fluctuating environment, they can even be maladaptive. What matters is whether the trait has a genetic basis (very likely for at least some depression), the frequency of alleles that determine whatever version of the trait we’re talking about, the relationship of the genes that affect this trait to other genes in the genome, and the effect of these alleles on the fitness of the individuals that carry them.

    Even more amusing is the assertion that humans have been selected for a certain environment as of 30,000 years ago. As other commenters have pointed out, recent history is also important for its selective potential. Geneticists can tease out examples of selection within the past 3,000 years, and even more recently.

    Many people have claimed that depression and other mental illnesses are adaptive. I find these claims to be rather unconvincing, and usually devoid of relevant data: genetic basis, frequency of alleles in the population, fitness of individuals with trait as compared to those without, plausible mechanism for selection on trait.

  61. daedalus2u says:

    Diomedes, as skeptics our default has to be “I don’t know”. Without data or theory to establish whether something like depression is an evolved “feature”, we have to default to “I don’t know”.

    Depression is seen in all cultures and all ethnic groups and has been present since antiquity. The custom in the early US was that when people killed themselves they could not be buried in a cemetery, so when you pass old graveyards and see graves outside the boundary, those are likely to be of people who killed themselves.

    My hypothesis about depression is that it is a “feature”, the necessary aversive physiological state between the normal “at rest” state and the euphoric state of near death metabolic stress as when running from a bear where to be caught is certain death. Running from a bear has to be a euphoric state if the organism is to escape and survive. Any level of damage is tolerable if it allows escape. That is why organisms can run themselves to death. Death from exhaustion and death from being caught are the same, an evolutionary fail. However, if organisms could enter a euphoric state easily, they would and would risk death needlessly. For stability in the euphoric state control system, there needs to be an aversive state between “at rest” and the state of euphoric near death physiological stress. Evolution has configured organisms to minimize the sum of deaths/non-reproduction from being caught by a bear, from dying from exhaustion and from suicide.

    Under this hypothesis, the whole point of depression is to be aversive. It has to be so painful and aversive that killing yourself is an attractive option. It has to be so aversive to limit entrance into the euphoric state which has to be so euphoric that you can do things that will kill you and feel good about it. You won’t find genes for this because it is from deep evolutionary time. Essentially every human has the capacity to become depressed, just like essentially every human has the capacity to become euphoric if being chased by a bear, even if they have never experienced it.

    Under this hypothesis, depression as a human disease is due to the inappropriate activation of the depressive state. It is the same pathways that trigger fight-or-flight that must also trigger the aversive state as an intermediate state. It is an skewing of physiology away from the at rest state. The opposite of what triggers fight-or-flight is what is needed to terminate the aversive state.

  62. Geoff says:

    @nybgrus

    Taking such a reductionist approach to cancer is important. If we want to fight cancer, we need to take a reductionist approach, understand the mechanisms, and try to figure out how to change them.

    That said, you seem to be losing sight of the forest for the trees. We have observed many cultures that do not have cancer over the last 150 years. Granted, most traditional cultures are not cancer free, but some are. The kitavans, the okinowans, the masai, the inuit, the tokeleau, aborigine, maori, etc. So the question of whether cancer is preventable or not has been answered empirically already. My hypothesis as to why is just that, a hypothesis, but it is not a wild guess, and it is absolutely steeped in evidence.

    I am aware that all cancers are as a result of a genetic mutation in cell replication, what I was referring to when I said “as a result of a genetic mutation” was different. For example, a friend of mine is studying a specific type of pancreatic cancer that seems to be caused by a genetic mutation. She has mice that have been bred for that mutation, and runs experiments on them. I’ve asked her multiple times to try and induce the cancer in those mice and treat with a ketogenic diet, but unfortunately she’s a peon at the moment and doesn’t have that kind of leverage in her work. I don’t know if this particular cancer could be prevented with an appropriate dietary intervention, and I don’t know if it can be cured by such an intervention. But I am convinced that some cancers can be treated, and the vast majority of cancers that we see today, in particular the ones I described above, can be.

    You clearly do not understand how science is conducted. In science, you evaluate the available data, formulate a predictive model (a hypothesis), and then test this model and see if the results were what we expected. That is all I have done. I have formulated a predictive hypothesis. I am confident of this hypothesis because I have tested it and seen other people test it on a n=1 basis, and because it is the result of evidence. That’s not assuming a conclusion before testing, that’s predicting a conclusion before testing. I am not “making the mistake that science will bear me out,” up to this point science has supported this hypothesis, and I have every reason to believe that it will continue to do so.

    @Harriet

    Just bought it on the kindle, will try to get to it over the next few months.

    @daedalus2u

    The questions are relevant because you are saying that NO disregulation is what is causing an upregulation of the fat mass setpoint, and that this NO disregulation is as a result of washing necessary bacteria off of our skin.

    So the question is, if this is what causes the NO disregulation, and the NO disregulation is what causes the uptick in the fat mass setpiont, then how does a tasteless liquid diet bring the setpoint back down? The relevant study is discussed here:http://wholehealthsource.blogspot.com/2011/05/food-reward-dominant-factor-in-obesity.html.

    I find this hypothesis unconvincing because it does not explain all of the phenomena that we see in the experiments. That is one example of this.

  63. Scott says:

    We have observed many cultures that do not have cancer over the last 150 years. Granted, most traditional cultures are not cancer free, but some are. The kitavans, the okinowans, the masai, the inuit, the tokeleau, aborigine, maori, etc. So the question of whether cancer is preventable or not has been answered empirically already.

    [Citation needed]

    I am confident of this hypothesis because I have tested it and seen other people test it on a n=1 basis, and because it is the result of evidence.

    You shouldn’t be. An n=1 test has effectively zero power to falsify the hypothesis, which means that all you have is a completely untested hypothesis. In other words, you’re the one who does not understand how science is conducted. You’ve almost completely skipped the critical step.

  64. vicki says:

    That’s funny, one minute of googling found me a report on the disproportionate impact of cancer on Maori versus non-Maori New Zealanders, including the observation that “The rate of cancer among Māori is only a fifth higher overall than among non-Māori.”

    This is from a few years back, and treatment and survival rates may have improved since, but it does show that the Maori do get cancer. So not even “citation needed” but “this is clearly false.” I have no reason to think that those other “traditional cultures” you refer to are cancer-free either.

  65. daedalus2u says:

    Geoff, the regulation of food consumption is not as simple as you want to believe. You are mixing models and not keeping consistent track of cause and effect, aka cherry-picking.

    How is the example of a synthetic diet resulting in normalization of weight consistent with your evolutionary diet hypothesis? What about a synthetic diet from a tube is “evolutionarily appropriate”? If eating a synthetic diet from a tube is all that is needed to restore normal weight, why isn’t it being done more? That paper was 45 years ago. Why isn’t there a “bland tasteless liquid diet” weight loss product?

  66. woo-fu says:

    @Becky Murphy

    said my son’s experiences with being traumatized were irrelevant

    Trauma is never irrelevant. This shows a poor understanding of the effects of stress and trauma on the part of that psychiatrist and the institution. Your son certainly deserved better.

    It is disturbing that no follow-up EEG was ordered if he showed signs of TLE on an earlier test. It also seems rather strange to me that schizophrenia was diagnosed at such an early age with the background your son had. Both PTSD and TLE, especially in children, can be mistaken for a host of other disorders. Good psychiatrists and psychologists know this and keep it in mind.

    I hope you have found more competent doctors to help your son. Know that he still has time to recover functioning. Medical treatments, as you and your son sadly know, can be a trauma in and of themselves. Finding someone your son can be comfortable with can help immensely.

    The real issue is Informed Consent and the fact that Psychiatrists and other mental health professionals, who take their lead from these “doctors,” do not in fact think it is important.

    Informed consent is a major issue for all doctors, not just those in the mental health field. I recently had to leave a doctor after an adverse drug reaction–a reaction I had specifically asked about in the doctor’s office–a reaction the doctor dismissed entirely.

    This wasn’t nearly the same thing as what you went through, but I want to point out that this problem is not limited to the mental health field. And I personally know there are plenty of caring, science-based mental health professionals who would be very concerned about your son’s experience. The trick, of course, is finding them.

  67. libby says:

    @ Becky Murphy:

    A very clear and detailed account of a family’s trip through hell.

    Part of the issue stems from the lack of effective regulation. In my area patient complaints are handled by the College of Physicians and Surgeons, which is essentially a body that protects physicians and surgeons.

    A well publicized case concerned a hospital surgeon whose infection rate was 10 times the average and included numerous botched surgeries.

    The Director of the College, in an interview with a TV reporter, was only concerned about how the information about the case had been leaked to the news agency. He ended the interview by prematurely walking out, without answering one question posed by the reporter.

    It turned out that the College had punished the surgeon after 100′s of complaints by moving him to different hospitals, and making him, no word of a lie, take a course in bedside manner.

    All of this is on public record thanks to some excellent investigative reporting.

    Doctors are people, and there are excellent doctors in conventional medicine. But when you establish a system where doctors have little concern over a regulatory body in place that is supposed to monitor their activities, some will take advantage of that situation.

  68. Geoff says:

    @Scott

    N=1 does have power to falsify a hypothesis. It takes one black swan to disprove the hypothesis that all swans are white. A well designed n=1 experiment absolutely can disprove a hypothesis, though it can never prove one.

    @vicki

    Yes, modern Maori are much less resistant to the toxic foods than New Zealanders of western heritage. This shouldn’t be at all surprising, and to me represents further evidence that these western foods are toxic in and of themselves, and that it is these foods that are causing the increase in the incidence of cancer. I am not denying that adaptation to modern foods has occurred, I am denying that we have become so well adapted to modern foods that they are no longer toxic to us in any amount. In my opinion, the “normal weight gain due to aging” that we see is actually our bodies eventually losing the uphill battle against toxic foods. This hypothesis would predict that aging on an appropriate human diet would look very different than aging on a standard american diet. Art DeVany would be an example of what aging is supposed to look like.

    I actually saw a video recently of a local NZ news channel feel good piece in which they were talking to modern Maori who were going back to a traditional Maori diet for weight loss. I believe it is the one referenced here: . Useless from a scientific perspective, but still cute, and a positive example of what I’m talking about.

    I was referring to traditional Maori, of which there were some who existed in the 1930s and likely more recently, although Weston Price’s study of them is the one I was referring to specifically.

  69. weing says:

    Wasn’t cannibalism widespread among the Maori people?

  70. Harriet Hall says:

    @Geoff,

    “modern Maori are much less resistant to the toxic foods”

    Unsupported speculation, both about resistance and about toxicity.

    “Weston Price’s study of them is the one I was referring to specifically.”

    Weston Price is not a reliable source of medical information.

  71. Harriet Hall says:

    @weing,

    Oooh! Cannibalism. If a group evolved to practice cannibalism, does that mean they should follow their evolutionary diet?

  72. Scott says:

    N=1 does have power to falsify a hypothesis. It takes one black swan to disprove the hypothesis that all swans are white. A well designed n=1 experiment absolutely can disprove a hypothesis, though it can never prove one.

    Depends on the hypothesis. Yours is (as I understand you; please correct me if I have misunderstood) that cancer may be prevented with a particular diet. N=1 has no power to falsify that, since the question which must be asked to falsify the hypothesis is “how does this diet affect the probability of developing cancer.” You can’t get any meaningful measurement of that probability without a large trial and therefore can’t falsify the claim.

    Unless, that is, your claim is actually that said diet prevents ALL cancer with 100% certainty. In that case it’s indeed true that N=1 could falsify the hypothesis. But it is also true that N=1 cannot ever reject the null hypothesis of no effect, and therefore cannot provide evidence for the claim. So even in the only case where N=1 could potentially falsify the hypothesis, it still cannot support it. Hence the hypothesis remains entirely unsupported.

    I also note that you’ve completely ducked the request to provide evidence for your claim that said populations are cancer free.

  73. daedalus2u says:

    Becky, that is a heart-breaking story of how your son was harmed by those supposedly taking care of him. I don’t know enough about the physiology of neuroleptics or atypical antipsychotics work to be able to comment on them. I do know a lot about stress, trauma and the PTSD that they can cause. I think the problems started or were exacerbated by the violence he experienced being abused by strangers and locked in a closet. Abuse and trauma will make just about every problem worse. I completely agree with woo-fu about that.

    I have a brother who had TLE as a child, this was 50 years ago (and a remarkably astute diagnosis by his physician) and he was put on dilantin. TLE and high IQ is often associated with being on the autism spectrum (where my brother is), not with schizophrenia or psychosis. My brother did things that could have easily have gotten him a diagnosis of oppositional defiant disorder. If he had been subjected to the things your son was subjected to he would have done badly. Anyone would have done badly when subjected to treatment like that. TLE can be very difficult to diagnose unless it it caught on an EEG when it is happening. The episodes can be transient and really hard to find.

    A quick check of google seems to indicate that psychosis with epilepsy is not common. You might want to get a second opinion.

    In my opinion, aversive treatments (such as are given at the Judge Rotenberg Educational Center which is being discussed in the news now as the state is discussing legislation to ban aversive treatments) should be banned.

    http://www.wwlp.com/dpp/news/politics/State-may-ban-%22shocking%22-school-therapy

    I think that aversive treatments make the underlying problems worse by triggering fight-or-flight and neuronal remodeling to facilitate entry into fight-or-flight more easily. For people on the autism spectrum, that can trigger a “melt-down “ where the person loses it. The “losing it” is physiology, not a conscious decision to be defiant or hostile, but some people can’t appreciate that people who are different can react in ways different than they want them to react.

    In the case of abusive treatment, causing the reaction is the objective that then post hoc justifies the abuse. That is what bullies do, abuse someone until they do something that justifies them being abused. Many people who bully are not consciously aware that this is what they are doing. I think those at the JRC are not aware that their aversive treatments are making things worse and not better.

    micwat, off label prescribing is when drugs are prescribed for something that the drug manufacturer has not gone to the FDA to get approval for. What indications a drug manufacturer tries to get FDA approval for is a business decision. Some indications are simply not worth the tens or hundreds of millions it would cost to get FDA approval. For generic drugs, there is no profit incentive for anyone to spend money to get FDA approval for a new use.

    The FDA is not there to regulate doctors, it is there to regulate food and drugs. It is drug and food manufacturers that are regulated by the FDA (mostly). There are some perverse incentives, once a drug has an approved indication, there is little incentive to do more research on it. The research doesn’t increase sales and might cause “problems” if the research finds something bad about the drug. This is the unavoidable outcome of the system that we have for discovering and bringing new drugs to market.

  74. Geoff says:

    @Scott

    My hypothesis is that like all animals, humans are healthy on an evolutionary appropriate diet. As such, all chronic disease is preventable through control of the most important lifestyle factors, namely diet, sleep, sun exposure and to a lesser extent exercise. Diet is by far the most important of these, as it is toxic substances in the diet that are actively harmful. The others help protect the body against toxic foods, rather than their absence causing anything (although extreme lack of sun exposure can result in vitamin d deficiency, and sleep deprivation can cause its own host of problems, particularly in the immune system). The primary neolithic agents of disease in the diet are wheat, excess linoleic acid and excess fructose, as well as hyper-rewarding food.

    Cancer is one example of something that can be prevented through an appropriate diet, however not by preventing the mutations from happening; though reducing systemic inflammation will reduce the total number of mutations; but rather by getting rid of cancerous mutations when they do happen. However, when I was referring to “my hypothesis” being tested on an n=1 basis, it was the above hypothesis, it wasn’t specifically about cancer.

    So the idea is that if the human body is naturally healthy, and capable of repairing itself, then removing the causitive agents from the diet should show DRAMATIC improvements in health over a very short period of time. So if you have high cholesterol because of a cascade of regulatory issues in the body that starts with the fact that you eat wheat on a daily basis, removing wheat should cause your cholesterol to normalize very quickly, as I stated above, in under 30 days in most cases.

    To me, the primary premise of this hypothesis, namely that humans are naturally healthy, is super obvious, and the fact that it is not accepted as a premise of all medicine is my primary beef with the SBM methodology. My main argument, from which the rest follows, is that evolution is the unifying theory of biology. As such, it is essential that with all experimental findings we take a step back and evaluate them in the context of our evolutionary history. Doing so helps us understand the likelihood that we have something right or probably missing something.

    As an example, let’s quickly glance at the idea that animal fat is in any way bad for us. While there is some epidemiological evidence, I think that there are a number of reasons to be very suspect of these findings, and look at them more from the perspective of “what variable are they missing from the analysis” rather than concluding that animal fat is harmful. The most important of these, of course, is strict physiology. When you eat an egg yolk, or a spoonful of butter, the solid triglycerides get broken into their free fatty acid parts before passing into the bloodstream. These fatty acids are structurally indistinguishable from fatty acids that come from our own fat tissue, that are manufactured by our own liver from carbohydrate via lipogenesis. So to say that fatty acids from the diet circulating in the blood stream are bad but fatty acids from our fat mass are alright when they are identical, well, that just doesn’t add up. Of course, it’s very well understood that losing weight causes dramatic improvements in all biomarkers of health, and I suspect that this is more about replacing calories from toxic foods in your diet like wheat with healthy animal fat from your fat mass.

    You can come at it from another way as well, since we are hunter-gatherers after all, and ate a large proportion of our calories from animal fat throughout our history. Our digestive tract is much more similar to that of carnivore species than herbivore species. We have an organ devoted just to the digestion of fatty acids. And of course, there are plenty of hunter gatherers who eat a huge proportion of their calories from animal fat, and yet don’t get heart disease, until of course they start eating wheat and sugar.

    Bringing it back full circle to the comment that started this particular thread, the idea that psych disorders could be caused by anything other than a chemical imbalance, in the most strict possible sense, is in violation of this premise. It is also in violation of my philosophical worldview, which states that we live in a deterministic universe, and everything that occurs is a product of the interaction of matter at the most basic level, and can, hypothetically, be modeled if we had better equations for the interaction of matter.

  75. Scott says:

    So even more vague and squirrely than I was giving you credit for, and therefore even less testable with N=1. In other words you have nothing more than speculation.

  76. WilliamLawrenceUtridge says:

    Yes, modern Maori are much less resistant to the toxic foods than New Zealanders of western heritage. This shouldn’t be at all surprising, and to me represents further evidence that these western foods are toxic in and of themselves, and that it is these foods that are causing the increase in the incidence of cancer.

    Bwahahahahahaha!!!!! Yeah, you play the toxin card here and you lose what credibility you may have had left. “Natural” foods, most fruits and vegetables, have chemogenic chemicals in them (aka flavour molecules) which the human body digests and detoxifies as a normal part of digestion.

    The Maori also used to die of infectious diseases, starvation, murder and accidents. Life was not idyllic as a hunter-gatherer.

    What are the “toxins” in modern foods then, can you name them? What evidence do you have that wheat causes high cholesterol?

    The idea that humans are “naturally healthy” is really quite mind-boggling. Even leaving genetic conditions out of the picture, humans exist in a hostile environment. Perhaps humans could be “naturally healthy” in a sterile bubble, but calling your idea “super obvious” looks a lot more like confirmation bias than anything else. It takes a massive investment of infrastructure, medicine and food subsidies for humans to live anything like a contemporary lifespan, and attempting to live on the diets of hunter-gatherers would lead a massive amount of th 6 billion people on the planet to starvation.

    So many targets and so little time. Is it just me or is there an unusual uptick in bizarre comments this month? I expect regression to the mean soon…

  77. Becky Murphy, my heart goes out to you and your son.

    Your story reinforces a thought that I had when reading HH’s article originally. Grouping a critique of adult psychiatric care and pediatric psychiatric care seems (IMO) to do neither justice. I know that there is some overlap, but with pediatric care you have special ethical concerns with treating children who are in different custody arrangements, (single parent, shared custody, state custody…) all of which have their individual possible pitfalls when it come to informed consent. The concerns that were raised few years ago about the extent that children were medicated for psychiatric conditions in the Texas foster care system is one example. (http://www.ahrp.org/infomail/04/11/13.php)

    It seems to me the question of off-label prescribing is also different between children and adults since many psychiatric medications have a good history of use in adults, but are relatively untested in children. Therefore one could speculate that the risk of off label prescribing may be much greater for children than adults. I wonder if this increased risk is accounted for in policy.

    Overall, I’m inclined to think a more indepth look at the individual problems in pediatric psychiatric care AND the U.S. social service system would be more helpful to children than a broad stroke indictment of U.S. mental health culture.

  78. reading my comment, I want to be clear that when I said “Overall, I’m inclined to think a more indepth look at the individual problems in pediatric psychiatric care AND the U.S. social service system would be more helpful to children than a broad stroke indictment of U.S. mental health culture”

    I was talking about the broad stroke indictment of Angell and the books she is reviewing, not Becky Murphy’s comment.

    Possibly, I’m making no sense at all.

  79. Harriet Hall says:

    @Geoff,

    “My hypothesis is that like all animals, humans are healthy on an evolutionary appropriate diet. As such, all chronic disease is preventable through control of the most important lifestyle factors, namely diet, sleep, sun exposure and to a lesser extent exercise.”

    You fail Logic 101. Even if your hypothesis is true that humans are healthy on an appropriate diet, that doesn’t mean that all chronic disease is preventable.

  80. Diomedes says:

    @daedalus:

    “You won’t find genes for this because it is from deep evolutionary time. ”

    What is this supposed to mean? That if a gene “originated” or “evolved” a long time ago we can’t detect it or its product/phenotypic effect? Nonsense. We detect ancient genes all the time in genomic analyses. Ever heard of HOX genes? We know what they do, and we know how old they are. Old enough that a fly, Drosophila melanogaster, and a mammal, Mus musculus, share the same basic blueprint for anterior/posterior development.

    We use genes from “deep evolutionary time” (a meaningless phrase anyway without any reference time) in evolutionary analysis. Ribosomal genes from the mitochondrial genome are regularly used to elucidate the phylogenetic relationships between organisms as disparate as coelacanths, cnidarians, arthropods, and mice. Whole genome analyses of plant genomes regularly detect wholesale genome duplication efforts, as well as isolate genes of interest for their phenotypic traits.

    There are a number of GWAS looking for the genetic basis of human traits, including mental illnesses like schizophrenia, bipolar disorder, and depression. GWAS have serious methodological and statistical issues, and these have prevented replication of early findings, but allelic variants that appear to confer risk for schizophrenia have been found, and (I believe) replicated. Findings on depression have been less supported, as far as I know.

    You’re also making the unfounded assumption that depression is inevitably accompanied by suicide. While many seriously depressed people commit suicide, the overall rate, while elevated compared to the rest of the population, is still low.

    Evolutionary psychology, a field with few rigorous standards of research, is rife with “scientists” who purport to establish that mental illness is adaptive. I have yet to see a rigorous and convincing study that incorporates all the evidence that, as an evolutionary geneticist, I expect from any scientific study that claims an adaptive advantage for any phenotypic trait or allelic variant: 1) a rigorous estimate of prevalence in the population, 2) a heritable basis (ie, a genetic basis), 3) a rigorous estimate of the effects of said variant on reproductive success, and 4) plausible and confirmed mechanism of selection on said trait. This data is currently absent for models claiming an adaptive advantage to any mental illness.

  81. Geoff says:

    @WilliamLawrenceUtridge

    I understand that there is some woo around the idea of a “toxin,” but I am using the word in a very specific way. Plants, because they are immobile, have anti-predation proteins in their seeds to prevent animals from eating them. Not all plants, but grains and legumes in particular do. These are evolutionary adaptations. Wheat as many of them, including gluten, as well as WGA, and some 20 odd others. They have evolved SPECIFICALLY with the purpose of hurting animals that eat them.

    Some of these, WGA in particular, can pass across the intestinal barrier undigested by mimicking part of an amino acid sequence of a natural enzyme that we produce as part of our body’s cut healing process. Others disregulate zonulin, causing tight junctions in the intestinal membrane to dissolve, and allowing many more proteins to pass across the intestinal barrier into the blood undigested.

    @Scott

    It is very testible on an n=1 basis. If someone has extremely high cholesterol, and they change their diet and it normalizes in 30 days, that is evidence. If someone is extremely overweight, and they change their diet and start losing 4+ pounds a week, that’s a data point. If someone is allergic to cats, and they change their diet and are no longer allergic to cats, that is a data point. If someone has rheumatoid arthritis, and they change their diet and reverse the disease process, a data point. Again, I have seen all of these on multiple occasions.

  82. Scott says:

    The problem is that you can’t be sure what’s due to the diet and what’s due to something else. Just to list one major potential confounder, those who make a radical dietary change are likely to start exercising more. Another would be that you’re making very specific claims about a very specific diet – you can’t really tell whether it’s the particular diet, or something particularly bad in their prior diet, or simply calorie restriction.

    There are good reasons these things are generally agreed to need large-scale studies.

    Keep in mind I’m not saying you’re wrong. I’m saying that the case is unproven, and firm judgement should be reserved until there’s good evidence.

  83. daedalus2u says:

    Diomedes, it is like how you can’t find genes for having 5 fingers, or genes for having two legs or for a 4 chambered heart. They are such universal characteristics of humans that there are no differential genetics because everyone has them.

    Yes, there have been GWAS looking for genes for neuropsychiatric disorders and they haven’t found anything beyond single or few gene deletions or duplications. The reason not much has been found is because those disorders are fundamentally not “genetic” in nature, they are emergent properties of a phenotype and not properties of a genotype.

    The largest GWAS I am familiar with is on autism, and looked at several thousand cases and controls and found no gene responsible for more than a few percent. The reason they can’t find “autism genes” is because there aren’t any. The ability to support an autistic phenotype is an inherent property of a human genome. If a genome can’t support an autistic phenotype, then it isn’t human and can’t support other human phenotype features.

    I am not assuming that depression is universally associated with suicide. I specifically said that evolution has minimized the death/non-reproduction due to being caught by a predator, running yourself to death and suicide from depression. That control paradigm predates vertebrates. Essentially every organism that can move and has sufficient sensory processing to detect predators will attempt to flee from a predator to the point of injury. Earthworms will rise to the surface and die from exposure to air, the Sun, and other predators in trying to flee their most frequent predator, the mole.

    http://en.wikipedia.org/wiki/Worm_charming

    Depression is also a property of a phenotype and not a property of a genotype. If a genotype cannot support a phenotype with depression, then that genotype is not human.

    Can you demonstrate that two legs are an adaptive phenotypic trait by the criteria you require?

    Does that mean you default to assuming that there is no adaptive reason for humans to have two legs?

    Two legs are a property of a phenotype not a genotype. All human genotypes will support the development of a phenotype with two legs. Treat a fetus with thalidomide at a certain gestational age, and it will not develop the two-leg phenotype that is characteristic of humans. That individual’s genome has not changed, and if that genome were grown in a thalidomide-free environment it would develop with two legs.

    Humans have a gigantic amount of plasticity in brain development. The development and growth of a brain is a property of a phenotype, not a genotype. The genotype is important, but is not separable from the environment because development couples to the environment at the level of noise. The human brain does this especially because human tribes needed diversity in cognitive skills that were not genetically determined. A tribe of closely related individuals needed diversity in cognitive abilities that couldn’t come from specific genes. That diversity had to come from the environment and environmental noise. That is sort-of like how diversity in antibodies comes from randomness. There isn’t one gene for one antibody, there is a system that mixes-and-matches and makes a great diversity of antibodies and then prunes away the ones that don’t work. That is sort-of-how brain development works, it mixes-and-matches and makes a great diversity of connections and then prunes away the ones that don’t work.

    All human genomes have the ability to support a large variety of brain phenotypes. Different exposures in utero, different life-histories, different experiences, different diets, different epigenetic programming from the parents will produce different phenotypes. All of those phenotypes are “normal”, that is they are “normal” as “process”, normal as in that they developed from a “normal” human genome with that genome acting the way it evolved to behave. Is the phenotype adaptive? Not always. Some exposures cause development to proceed in ways that are maladaptive, such as thalidomide exposure at a certain time.

  84. Geoff says:

    @Harriet

    H = perfect health = the absence of disease
    D = chronic disease
    Therefore: H = ~D

    L = perfect lifestyle
    Expressed this way, my hypothesis is L –> H

    Since L –> H and H = ~C, therefore D –> ~C

    Where’s the logic fail here?

  85. Justin says:

    How I interpret “neuropsychiatric disorders are not a result of chemical imbalance” is that rather than an imbalance, this is the natural result of a particular set of genes interacting with the environment over a lifetime, most importantly including the developmental timeframes, in utero, birth to 5 years, and adolescence (the GxExD model). These are all timeframes where interaction of genes and environment can have long lasting effects on how neuronal networks are shaped, as well as other physiological traits that can affect brain chemistry. So, it’s not an imbalance per se, but rather a different neurodevelopmental trajectory that was uniquely shaped by the individual’s genes and environment.

    This concept gains traction when you look at the large variability between symptoms and the inability to pinpoint any single genetic cause or “chemical abnormality” between psychiatric patients. This is why a DSM classification is not always that helpful and occasionally detrimental. This sort of quasi-objective classification doesn’t tell you anything about the unique biology of the individual, but rather groups people based on subjective interpretations. This doesn’t mean throw the DSM out all together, but it does mean that a more objective measuring system needs to be developed for many different psychiatric “disorders”, so that a “history” doesn’t dictate your future.

    This is currently the case with major depressive disorder. The emerging finding that MDD often correlates well with proinflammatory cytokine biomarkers is a step in the right direction. This is interesting in the sense that a completely Non-CNS physiological issue can trickle down and effect behavior. It makes sense though, if you understand the immune system to be one of the “senses”. Normally, when a person gets sick, behavior has to adapt to the situation to afford the greatest chance of survival, this behavior is modulated via cytokines (immune signaling proteins) and is commonly referred to as sickness behavior. From an evolutionary standpoint, the organism that appropriately attenuates its behavior to survive an illness will pass on its genetic material. It also hints at why these types of mechanisms can persist, and that is simply because they are beneficial to the survival of the organism. However, there can be a point where this normal mechanism can have a detrimental impact on the organism. This is the case with depression (at least the cases which are potentially caused by the over active immune system). In these cases the person has no overt or active infection, but has a higher level of certain proinflammatory cytokines which trick the brain into going into a different behavioral state by modulating the appropriate neuronal networks and this behavior state, in the absence of infection, is certainly not helping anything. The question that arises is: why does this person have a higher level of inflammatory cytokines if this person doesn’t have an active infection? The answer is genetics, environment and development. All of these factors have to be explored to understand how the person got to where they are.

    I think this is where Geoff may have a point. Arguably the most important environmental factors which may influence the inflammatory status of the body are stress and diet(when infection isn’t indicated). Furthermore, both of these factors highly influence the composition of the intestinal microflora. Since the number of bacteria making up the microflora is an order of magnitude greater than the cells in our body, the microflora has a profound impact on the cytokine milieu at any given moment. There is much more to say about this topic but this post is getting into TLDR territory so I will follow up later.

  86. Harriet Hall says:

    @Geoff,

    You aren’t even consistent. Your first statement was “humans are healthy on an evolutionary appropriate diet” and now you have substituted “perfect health.” You have no evidence that even the most optimum diet and lifestyle could ensure “perfect health” or prevent all chronic disease. I have pointed out evidence from cancer science that disproves that assumption. You have not established that there is any such thing as “perfect” health.

    By the way, since cannibals apparently evolved to eat human flesh, and since there is archaeological evidence for cannibalism in our human ancestors, and primates and many other mammals are known to eat their own kind, do your evolutionary imaginings indicate that their descendants should eat human flesh today to stay healthy? And should women routinely eat their own placentas?

  87. nybgrus says:

    @Geoff:

    Oh dear, this again…. where to start:

    We have observed many cultures that do not have cancer over the last 150 years. Granted, most traditional cultures are not cancer free, but some are. The kitavans, the okinowans, the masai, the inuit, the tokeleau, aborigine, maori, etc. So the question of whether cancer is preventable or not has been answered empirically already.

    Sorry, but I’ve already shot that one to pieces the last time you came on here spouting your “theories.” Ancient Egyptians had cancer. Traditional cultures have cancer. Cancer is a disease of old age. If you don’t live long enough (as in most traditional cultures) you don’t get much cancer. You have zero reliable data to back up a statement like this. Here is your first wrong assumption.

    I am aware that all cancers are as a result of a genetic mutation in cell replication, what I was referring to when I said “as a result of a genetic mutation” was different.

    Brilliant tactic. Say you are aware, then say what you were saying is different, and then never explain why or how it is different and expect it to just be done. QED

    Oh wait, you said “for example” to explain what you meant:

    For example, a friend of mine is studying a specific type of pancreatic cancer that seems to be caused by a genetic mutation. She has mice that have been bred for that mutation, and runs experiments on them. I’ve asked her multiple times to try and induce the cancer in those mice and treat with a ketogenic diet

    Oh, no that doesn’t even remotely address the point. So you haven’t even managed to get past that point Geoff. But lets see where you were going with this:

    but unfortunately she’s a peon at the moment and doesn’t have that kind of leverage in her work. I don’t know if this particular cancer could be prevented with an appropriate dietary intervention, and I don’t know if it can be cured by such an intervention. But I am convinced that some cancers can be treated, and the vast majority of cancers that we see today, in particular the ones I described above, can be.

    Aha! conspiracy gambit. Nice. “She could do the research, and totally wants to cuz she knows my ketogenic diet ideas are sooo money, but the man is keeping her down, man.” But hey, you are convinved you are right, aren’t you? So sure, we can confirm that hypothesis you have which is already based on false assumptions, because the fact that the man won’t let your researcher friend do tests with her knockout mice is further evidence of that.

    You clearly do not understand how science is conducted. In science, you evaluate the available data, formulate a predictive model (a hypothesis), and then test this model and see if the results were what we expected.

    Wow! Pot calling the kettle black much these days? The funny thing is you do actually describe roughly how science is conducted. The problem is you don’t have a grasp on the necessary background to formulate a good hypothesis (failure in science #1) and you are convinced of your conclusion before testing your bad hypothesis (failure in science #2).

    I am not “making the mistake that science will bear me out,” up to this point science has supported this hypothesis, and I have every reason to believe that it will continue to do so.

    compare with:

    But I am convinced that some cancers can be treated, and the vast majority of cancers that we see today, in particular the ones I described above, can be

    Internal logical consistency is not your strong suit.

    My hypothesis is that like all animals, humans are healthy on an evolutionary appropriate diet.

    Like all animals? Once again, an evidence free assertion (and wrong to boot).

    Cancer is one example of something that can be prevented through an appropriate diet, however not by preventing the mutations from happening; though reducing systemic inflammation will reduce the total number of mutations; but rather by getting rid of cancerous mutations when they do happen.

    And how, pray tell, can diet effect a change on a molecular level and have any bearing on oncogenesis? As we have established before, you really do not have an understanding of cancer biology and consistently make gross errors as a result. Dr. Hall told you to read that book – I wouldn’t put it off for months. You need to understand oncogenesis now so you stop making stupid assertions like that. (not knowing the basics of what you are hypothesizing about, science faiure #3 – yer out!)

    So the idea is that if the human body is naturally healthy, and capable of repairing itself, then removing the causitive agents from the diet should show DRAMATIC improvements in health over a very short period of time.

    Once again, you are making an assumption that is in no way reasonable or based in evidence and using that to base your hypothesis on. How many times to I have to point out that you are doing this and that this is NOT science before you get it?

    to me, the primary premise of this hypothesis, namely that humans are naturally healthy, is super obvious, and the fact that it is not accepted as a premise of all medicine is my primary beef with the SBM methodology.

    Oh, never mind. You premise is “super obvious.” Well, that should be good enough for the journals right? Perhaps I can get something published in JAMA or the NEJM by writing the editor and telling them it is “super obvious” and they should like, totally print it! (assuming premise to be true based on nothing but “its super obvious,” science failure #4)

    We have an organ devoted just to the digestion of fatty acids.

    And what organ might that be, Geoff? Saliva has lipase. The liver has lipase. The pancreas has lipase. Each one has other functions. Or perhaps you were thinking of the gallbladder? It aides in the digestion of fat by giving some emulsifiers, but it isn’t devoted to the digestion. In fact, you can remove the gallbladder and still be just fine. (asserting basic physiology facts that are wrong, science failure #5).

    And of course, there are plenty of hunter gatherers who eat a huge proportion of their calories from animal fat, and yet don’t get heart disease, until of course they start eating wheat and sugar.

    Yet another evidence free assertion and assumption you must make for your theory to hold any water. Sorry Geoff, you still haven’t even gotten past this.

    It is also in violation of my philosophical worldview, which states that we live in a deterministic universe, and everything that occurs is a product of the interaction of matter at the most basic level, and can, hypothetically, be modeled if we had better equations for the interaction of matter.

    Science failure #6 – using a worldview to inform a hypothesis rather than the evidence

    They have evolved SPECIFICALLY with the purpose of hurting animals that eat them.

    But you aren’t talking about getting poisoned Geoff. Nice dodge there, but those are not the “toxins” to which you are referring.

    And lastly (I have to limit this a bit… I could essentially do this for every sentence you write):

    H = perfect health = the absence of disease
    D = chronic disease
    Therefore: H = ~D

    L = perfect lifestyle
    Expressed this way, my hypothesis is L –> H

    Since L –> H and H = ~C, therefore D –> ~C

    Where’s the logic fail here?

    The logic fail starts with H = the absence of disease; that is an evidence free and baseless assertion (and wrong). Next is L –> H; another evidence free assertion. There is no evidence or reason to believe that a “perfect lifestyle” will lead to “perfect health.” Next is the fact that you introduce variable “C” which is not defined and I can’t figure out where the hell that came from.

    So that is about as utter a logic fail as you could have possibly demonstrated. The only single line that even has logical internal consistency is “therefore H = ~D” but that is based on false assumptions, so is therefore incorrect, despite being literally the ONLY logical thing you’ve written.

  88. Geoff says:

    @Justin

    I did my best to leave room for what I labeled “permanent damage” by which I meant not necessarily just damage but changes to the developmental structure that cannot be reversed, which sounds a lot like what you are describing. I do think that the biochemistry in and of itself plays a role though as does systemic inflammation, both of which are directly related to dietary factors in my opinion. So someone can have a brain that developed properly, and still develop depression once they are fully grown, and this depression can be completely reversed through lifestyle interventions. People with more serious conditions can still get relief through appropriate dietary interventions, but it will not necessarily totally cure it. I have seen this first hand with a couple of women I have dated who in their past had dealt with eating disorders

    At this point in my thinking, I am starting to believe more and more that a chronic stress response is a symptom rather than a cause. To put it another way, people with healthy brain biochemistry do not experience chronic stress. Maybe people with stressful jobs get less sleep on average, or eat more fast food on average, or any number of correlative factors that could dramatically increase stress hormones, specifically cortisol. My evidence for this is extremely weak, more an observation than anything else, so I’m not in any way married to this idea, but it’s definitely the direction that I am leaning toward at the moment as far as the direction of causation.

    @Harriet

    My primary evidence for the absence on disease is the anthropological data that you refuse to accept, so this is always going to be a point of contention. If we do choose to accept the anthropology as true to its claims, however, these cultures do serve as a negative example disproving the hypothesis that it is impossible for entire groups of people to be free from chronic disease.

    I have never seen any cancer study in which someone was fed a paleo 2.0 diet from birth, so I’m not sure what you are claiming when you say that you have disproved my hypothesis about cancer being preventable through a proper diet.

    Cannibalism undoubtedly happened, but I do not think that there is any reason to believe that eating human animals would be substantially different from eating any other omnivore’s meat. I can give at least one example in which a traditional culture resorted to cannibalism during famine with the specific purpose of including at least a small amount of meat in their diet so that they would not get nutrient deficiencies that they knew would result in tooth decay and crookedness. http://www.westonaprice.org/blogs/cmasterjohn/2011/05/12/weston-price-looked-for-vegans-but-found-only-cannibals/

    Let’s write that off as a specific example of why I think that is good to look at nutrition information in traditional cultures for the sake of understanding our own health, but at the same time I am also thankful that I live in a society in which being attacked by a neighboring tribe for my meat is not a serious concern, i.e. why I am interested in replicating the evolutionary metabolic milieu, but not interested in a reenactment.

  89. Geoff says:

    @nybgrus

    Yep, the C was supposed to be a D. In my first iteration of writing that out, I used C for chronic disease, and in my second I used D for disease. Definitely a logic fail there. However, L –> H is the assertion that Harriet said “even if you assume that humans are healthy on an appropriate diet.” This if statement represented that assumption. She was saying that my logic was flawed even with that assumption, which I refuted with that logical argument.

    Ancient egyptians had very little cancer. Some, but proportional to heart disease, which is also a disease of age, though definitely less so, substantially less than we have today. The other traditional cultures mentioned had near zero levels. Not completely zero, but very close, certainly as compared to modern standards.

    If cancer is a disease of old age, then why don’t centenarians all eventually die from cancer? In fact, it’s the exception, rather than the rule, that centenarians die of cancer. Cancer is very uncommon.

    I was referring to the gallbladder. What are the other functions of the gallbladder other than the secretion of enzymes for the purpose of digesting fat?

    I have to leave, so as much as I’m enjoying the tone of where this is going, I’m not going to have a chance to go line by line and dispute all of your refutations, but by no means are your refutations in any way objective or above dispute.

  90. nybgrus says:

    My primary evidence for the absence on disease is the anthropological data that you refuse to accept, so this is always going to be a point of contention. If we do choose to accept the anthropology as true to its claims, however, these cultures do serve as a negative example disproving the hypothesis that it is impossible for entire groups of people to be free from chronic disease.

    There is a reason… because the data is wrong. I don’t know if I have mentioned this to you before, but I have an entire degree in medical anthropology, graduated with honors, and can tell you the studied you cite are garbage. You cannot make scientific claims onsuch studies. It is not a “point of contention” it is a point of you being flat out wrong.

    But more to the point, you can’t even address the basic science of the ketogenic diet vis-a-vis cancer – I challenged you before, as did Dr. Hall, and you can’t get past that either.

    You use bad studies as the basis for false assumptions. You don’t know cancer biology or oncogenesis. You can’t cite any data regarding a ketogenic diet that would adress any of these issues. Yet you are convinced your hypothesis must be correct.

    You fail on every level of scientific inquiry and this has been pointed out numerous times by myself, Dr. Hall, and many others here. Instead of continuing plowing through try and learn why we are saying you are wrong, and start with learning about cancer biology if you genuinely care about this topic, instead of just caring about your pre-conceived conclusion.

  91. nybgrus says:

    My objections are pretty spot on, but of course nothing is “beyond dispute” You havent addressed any of the basic points to make your theory. Your assumptions are invalid, period.

    You also make really bad dichotomous assertions:

    If cancer is a disease of old age, then why don’t centenarians all eventually die from cancer? In fact, it’s the exception, rather than the rule, that centenarians die of cancer. Cancer is very uncommon.

    Just because it is a disease of old age doesn’t mean everyone who is old gets cancer. That is just a downright stupid statement. If you look at the incidence of cancer it VASTLY increases with age. Why wouldn’t centenarians ALWAYS have cancer? Because they are part of a population that survived being octegenarians.

    I was referring to the gallbladder. What are the other functions of the gallbladder other than the secretion of enzymes for the purpose of digesting fat?

    First off, the gallbladder does not secrete anything, nor does it excrete any enzymes. It stores and concentrates bile which is a waste product and aides in digestion. Bile does not itself digest fat, it emulsifies it. A complete lack of bile certainly impairs fat digestion but does not completely impede it. So in other words, characterizing it as “an organ devoted entirely to fat digestion” is simply false. Yet another demonstration of your lack of basic knowledge.

  92. woo-fu says:

    @Micheleinmichigan

    You make perfect sense to me. Ms. Murphy’s story highlights the complexity of realistically handling these problems. And I think your analysis helped to illustrate that very well.

    Social services are continually being scaled back in many states, and many of the services are lacking to say the least. This is especially true where available foster homes are few and institutions for children are overcrowded. Often times children in these circumstances end up living in juvenile detention centers, whether warranted or not. That in and of itself can cause major trauma. Add to that a lack of consistent, transparent and thorough oversight, and the outlook gets even more grim.

    Trying to assess and deliver appropriate medical care, especially psychiatric care, to children in such circumstances is an extremely difficult task. As you’ve stated, children are still developing. Normal childhood behaviors (especially those exhibited in rather abnormal situations) are often mistaken for mental illness and are inappropriately medicated. And even when medication is clearly indicated, there still isn’t enough solid research to determine the effects of psychotropics (generally designed and tested on adults) on children, especially when intended for long-term use.

  93. Diomedes says:

    @daedelus2u

    “Can you demonstrate that two legs are an adaptive phenotypic trait by the criteria you require?

    Does that mean you default to assuming that there is no adaptive reason for humans to have two legs?”

    Good point, but the criteria I proposed would be most appropriate for determining adaptive advantage within populations. Which is exactly the kind of trait we’re talking about. Depression is a phenotype that varies within the population of humans. The two-legs issue is more one of paleontology.

    You claim to be a skeptic and say that, as skeptics, we must all assume that “we don’t know.” Then you suggest that these traits are essentially not genetically determined in any meaningful way. That’s not “we don’t know”. That is a hypothesis. It may be correct. However, your dismissal of GWAS is completely out of hand. GWAS are consistently troubled by methodological issues, yes. Meanwhile, our expectations of finding one or two genes to determine a phenotype like depression, which is complex, are off base and not biologically or genetically realistic.

    GWAS are consistently underpowered. Consistently. Many traits, including such “simple” traits as height, etc, are proving to be largely genetic, with heritability estimates of 80-90% (from twin studies), yet our search for “height genes” has been largely unsatisfactory for those expecting to find one, or a few, or even 10. Height appears to be determined by many, many genes with many, many rare segregating alleles in the population. The fact that GWAS for neuro-psychological traits like autism and depression have been largely disappointing in terms of convincing candidates and replication is by no means evidence that these traits are “phenotypic” and not “genotypic” as you claim.

    (These are terms that I generally do not hear used this way in the genetics department that I work in. Maybe that’s a human genetics thing? To say a trait is “phenotypic” says nothing whatever about its genetic basis. And what exactly is a “genotypic trait”? To claim that depression has a genetic basis means nothing more nor less than to say that some version(s) of alleles of some genes predispose individuals to express it. Is the environment involved? Of course, and I’m not aware of any scientist who would claim otherwise. But your distinctions between “phenotypic” traits and “genotypic” traits are not standard.)

    “Diomedes, it is like how you can’t find genes for having 5 fingers, or genes for having two legs or for a 4 chambered heart.”

    Why not? If I wanted to find what genes, and what versions of those genes determined the evolution of five fingers, I could do that using comparative genomics. I would look in the genomes of mammals, look at a phylogeny, determine the order of evolution of these phenotypic traits (tarsus number), look at how they are expressed in other mammals,and determine which change appeared to be important. These things typically don’t happen in human genetics as much as they do with mice or rats because of the ethical issues involved in working with humans (for example, the experiments needed to confirm the action of the gene), but it’s certainly theoretically possible possible. It’s a technique that is used all the time in sticklebacks, arabidopsis, maize, mice, whatever. Humans are not model organisms and so we are limited in what we can do with them, but to imply that I can’t determine which genes were involved in the evolution of major traits a long time ago is nonsense.

  94. Becky Murphy says:

    thank you for the responses to my comment. I would like to respond to the comment about the mental health system in the US.

    My son has been an adult for 5 years, and he doesn’t believe any psychiatrist has listened to him since the experiences I speak of in my previous comment, I assure you his perceptions are spot on.

    Last July he for the first time in 5 and 1/2 years had a crisis precipitated by his remembering his long term hospitalization and how it had traumatized him—the quotes in my prior comment are from this time. His brother and I accompanied him to the crisis center. where we were lied to and a Designated Mental health professional committed perjury and forged a affidavit to have him detained involuntarity. A psychiatrist on staff at this same facility committed perjury and further court ordered my son to the drugs he prescribed—one of which was a benzodiazepine he had been taken off of due to cardiac damage and further risk. The withdrawal was horrible and drawn out. This psychiatrist consulted no one–not my son’s primary dr. or his current mental health provider, or psychiatrist–in fact he spoke to NO ONE who knew my son, not me or his brother. He did have the information about the fact my son had been taken off of the benzo and why; yet he put him back on it at TWICE the dose. He also increased the clozapine by 250mg all at once—it is recommended to increase this particular drug by no more than 100 mg at a time no more often than twice a week. The prosecutor who I had spoke to 3 times before the last hearing—submitted what he had to at least suspect was false testimony yet did no fact finding. My son’s attorney put on no defense, in fact in the one minute and twenty-six second hearing, the only voice heard is my son’s legal advocate putting on the Prosecutions case, and the judge granting the order. My son, who is a 6’3″ young man was so traumatized by these events that once home he was afraid to leave the house for over two weeks—would not even go in our own yard.

    I tell you this because it is what is being done, this series of events from last summer is the NORM in this Country. I am a good mother, every time my son has been victimized by mental health professionals or any one I have filed the appropriate reports with Law enforcement and other appointed authorities, NOT once has these complaints been investigated, because when the victim has a psychiatric diagnosis, crimes against them are seldom, if ever investigated.

    The prosecutor is no longer a prosecutor, but he has not been charged with a crime and neither have the two “mental health professionals” who committed felony crimes; these crimes are punishable by up to ten years in prison—My son is a trauma victim, and I am so very grateful that I know that what he said the problem was from the beginning was important and valid—I am grateful that he trusts me and his brother.

    Washington state has some of the worst laws in the Nation for Involuntary Commitment but, stories like ours are not uncommon—I just happen to be a person who will not be silenced and who will not back down.

    From my blog on my about me page:

    “If my life, and what was done to my son and my family means anything at all, it’s meaning for me must be derived from sharing what I have learned and working to keep it from happening to anyone else. I must share what I’ve learned to hopefully spare another family the same experiences. None of us will ever ‘be the same’ and life can be bittersweet. My sons and I agree that we need to reach out to others offering hope and whatever assistance we can. I am grateful to know the truth.”

    I have ethics and integrity because my parents had ethics and integrity, and because I need to meet my own gaze in the mirror when I brush my teeth.

  95. daedalus2u says:

    I am not saying that genetics is not important, what I am saying is that genetics cannot be looked at or considered independently of the environment, and the “environment” encompasses everything down to the Brownian motion that buffets the DNA and transcription factors during transcription. There isn’t, and can’t be a description of the environment at that level of detail, so what a genome is going to do will always have a large degree of uncertainty.

    Every human will exhibit depression under certain circumstances. We can’t put people under such circumstances because it is torture and is extremely damaging. Every person who has been tortured severely enough has become “broken”. The “genes are everything” approach posits that people who become depressed are fundamentally different at the level of the genome from people who do not become depressed, no matter what environments they have been in, and the most important environment (the in utero environment) is completely unknown.

    When you say a trait like height is largely genetic, yet it doesn’t meet the criteria you require when other people say something is largely genetic, what does that mean? I would like those criteria to be able to say something is genetic too. Twin studies don’t use those criteria.

    You can’t trace the evolutionary history of something like height that depends on hundreds of genes. In principle you can, but in practice it takes too much data, data which you can’t get and even if you could get it, there is no computer system that could analyze it.

    When you say that a GWAS is “underpowered”, that is equivalent to rejecting an n=1 anecdote because it is underpowered. The GWAS with several thousand subjects are equivalent to anecdotes because the genetics is so complicated that studies with several thousand subjects don’t provide enough statistical power.

    The GWAS studies in autism have shown that no gene confers more than a few percent of the propensity to get autism. If it is 100% genetic, that means there must be at least 50 genes (each at 2%). 50 factorial is 3x10e64. So far there have only been something like 10e11 humans. There will never be a GWAS trial with 10e64 subjects. If you can’t analyze something that takes 50 genes, what does that mean for more complex things?

    We know it takes more than several thousand subjects to get sufficient statistical power from GWAS. How many more we don’t know yet and we won’t know until we do a study large enough that statistically significant results are found. What does that data point tell us about the statistical power of the twin studies that have been done? It tells us that what they are saying about genetics is under powered too.

    MZ twins share an in utero environment where their brains grow from a single cell to ~10e11. Yes, they do share a genome, but they also share that in utero environment. The gene researchers would like to think that the genetics and the environment can be looked at independently, and linearly. We know that is incorrect because the genetics and environment are coupled and that coupling is non-linear. Non-linear coupled systems exhibit chaos when there are a few variables (two or three). They are inherently unpredictable. What happens when there are thousands or tens of thousands or millions? The GWAS studies are underpowered using an independent and linear model. What if they used the correct approach of coupled and non-linear?

    Suppose MZ twins were exposed to thalidomide in utero, unknown to the mother and both had characteristic birth defects. The protocol of the twin studies would call those characteristic and shared birth defects “genetic”. What other in utero environmental effects would be considered to be “genetic” if exhibited by MZ twins? As I understand MZ twin studies, all of them.

    I appreciate that there is a gigantic fetish in science these days to do genetic stuff. That fetish is unfortunate because it blinds people to the non-genetic stuff that is going on. The genome is so complicated that a blind “genes are everything” approach is going to fail.

    There needs to be more funding on treatments and on trying to understand how physiology works. A blind gene search is simply not going to work, but blind gene searches are all that the big gene sequencing factories can do and then need to keep their expensive hardware busy sequencing DNA.

    The current genetic approach to neuropsychiatric disorders has a lot of appeal to people without the disorders. They get to “other” people with the disorders and imagine that somehow they are fundamentally different from “those” with the disorder because they have different genes. This is why the idea of the genetic basis of intelligence has had such a wide following. But they can’t find the genes for intelligence either.

    I think that is why the concept of neurodiversity is so important. It is the neurodiversity of humanity that is our greatest strength, not the conformance to something “normal”. Not every human brain can instantiate every idea that every other human brain can instantiate. Labeling brains that can instantiate unique ideas as abnormal may be technically correct, but forcing that human brain into a “normal” pattern (or more typically “breaking it”) where it can no longer instantiate that unique idea is a terrible waste unless we first analyze that unique idea and find out if it is correct or not.

  96. DW says:

    Geoff:

    Perfect lifestyle > perfect health

    What?

    people with healthy brain biochemistry do not experience chronic stress

    What?

    I might say it is super obvious that these things are not true.

  97. DW says:

    “If cancer is a disease of old age, then why don’t centenarians all eventually die from cancer? ”

    Oy. You exhibit many failures of basic reasoning – never mind scientific reasoning. Do you not understand why the latter does not follow from the former?

  98. weing says:

    “Some of these, WGA in particular, can pass across the intestinal barrier undigested by mimicking part of an amino acid sequence of a natural enzyme that we produce as part of our body’s cut healing process.”

    References please? All I can find is some unreferenced claims on chiropractic web sites.

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