a powerful message…

Posted on Sunday 8 April 2012

In my post on the neuroimaging study of depressed kids [wary skepticism…], I deliberately avoided the accompanying editorial that went with it. After all, it is a holiday, but it needs mentioning. From my reading, Dr. Tao’s study [Brain Activity in Adolescent Major Depressive Disorder Before and After Fluoxetine Treatment] is hardly definitive, and colored by association with senior author Graham Emslie who never found an antidepressant that he didn’t think helped children. He was an author on all four of the Prozac studies used in the Gibbons meta-analysis [more clearly III…], the infamous Paxil Study 329 [Efficacy of Paroxetine in the Treatment of Adolescent Major Depression], a Lexapro study in kids [Escitalopram in the treatment of adolescent depression], and has appeared with Dr. Gibbons in a Forest Laboratory financed Medscape C.M.E. touting the wonders of antidepressants in kids. So in the same issue of the American Journal of Psychiatry as Dr. Tao’s study, we have this editorial:

Imaging Adolescent Depression Treatment
by Kathryn R. Cullen, M.D.
American Journal of Psychiatry 2012 169:348-350.

In this issue of the Journal, Tao et al. report the first results from a neuroimaging study examining the neural circuitry in adolescents with depression before and after treatment. This type of research has been greatly needed in a field in which most imaging studies of depression (especially with regard to treatment) have been conducted in adults. Because of ongoing brain development during adolescence, the neural mechanisms that underlie the disorder could be distinct. Similarly, the mechanisms underlying treatment response in adolescents may be different from those in adults, given increased neuroplasticity during the adolescent period. Furthermore, examination of these mechanisms during early phases of the disorder provides the opportunity to avoid confounds due to complex treatment histories or potential scarring from years of disease. Most important, a better understanding of adolescent-specific mechanisms will be a critical foundation for the advancement of early interventions, which could significantly affect public health…

The findings reported by Tao et al. are exciting and open up new avenues for research. The next steps in this field must strive to disentangle the numerous contributors that likely affect both baseline and post-treatment findings: age at assessment, age at onset of depression, lifetime burden of illness, illness status [e.g., familial risk, first episode, remission, relapse], treatment history, and type of treatment. Addressing these issues through careful research that takes advantage of recent progress in neuroimaging approaches and that uses precision in reporting result locations holds great promise for the field. Mapping out these biomarkers will be the key to enabling the clinical advancements needed to allow patients to achieve remission in the earliest phase of illness, bringing adolescents back on course for healthy development and thus circumventing a host of potential negative consequences over their lifetime.

In her editorial, she briefly acknowledges that the significance evaporated when corrected for multiple measures in a single word, but carried on as if that were immaterial, "the voxel-wise analysis of this adolescent study revealed higher activation in the depressed group in multiple (uncorrected) clusters within the frontal lobe." But the thing that caught our attention was the elevation of this study to the clinical realm, " from a clinical perspective, as the authors point out in the discussion section, this research provides a powerful message that clinicians can give to families: adolescents with depression have abnormal neural circuitry, and treatment with fluoxetine will make the circuitry normal again." This comment, which is a massive over-reading of the Tao study in any dimension, reminds me of a comment from Dr. Insel this Fall:

The field of mental health is on the cusp of a revolution, which is set to transform the diagnosis and treatment of mental illness and reverse the lack of major progress made in curbing associated ill health and death over the past 100 years, the director of the US National Institute of Mental Health, has claimed. “We are at an extraordinary moment when the entire scientific foundation for mental health is shifting, with the 20th century discipline of psychiatry becoming the 21st century discipline of clinical neuroscience,” Thomas Insel said before a meeting on the challenges facing mental health research at the Royal Society in London on 31 August…

The seismic shift had been driven by what he described as three “revolutionary changes” in thinking, the first of which was that mental illness was increasingly being recognised as a disorder of brain circuitry, rather than as a chemical imbalance, thanks to neuroimaging techniques and the discovery of some key biomarkers. Secondly, mental ill health was now recognised as a developmental disorder for which early intervention was vital, said Professor Insel, highlighting US research showing that 50% of study participants had reported the onset of mental health problems by the age of 14, and 75% by the age of 24. “We are still stuck with getting to the problem very late. The future will be about understanding the trajectory of illness so that we can identify the first signs before it develops into psychosis,” he said…
I think this must be how things have worked in the not so distant past. Tao’s study is provocative. It may have shown the measurement of blood-flow changes in the brain to facial image stimulus  or it may not. It may have shown differences between depressed and normal kids, or it may not. It may have shown a change with medications, and it may not. I thought I was being generous to say after several readings that in spite of the lack of statistical validation, it was interesting and worth pursuing – an early run at something that might bear fruit down the line. But in this editorial, it has been elevated to the level of truth, a great message for depressed adolescents and their parents. Prozac normalizes abnormal brain circuitry in depressed kids. Or as Tom Insel says, "mental illness was increasingly being recognised as a disorder of brain circuitry, rather than as a chemical imbalance, thanks to neuroimaging techniques and the discovery of some key biomarkers." Give us a —-ing break! This is how a study like this gets into the literature as "recent advances in neuroimaging…" And even if everything in the Tao study were rock solid [which it certainly isn’t], this statement would hardly be justified: "adolescents with depression have abnormal neural circuitry, and treatment with fluoxetine will make the circuitry normal again." This is the exact kind of bull-shit exaggeration that has made a laughing stock of psychiatry and neuroscience; that has caused so many people to be on medication that they would’ve been better off without; and they’re trying to do it again…
hat tip to Nancy…   
  1.  
    aek
    April 9, 2012 | 8:56 AM
     

    I appreciated your take on this very much, Dr. Nardo. As a long time critical care nurse and educator, I witnessed an enormous transition in thinking about the care and treatment of myocardial infarctions (heart attacks). Care and treatment initially and historically was focused on complete bed rest and inactivity – up to and including only allowing room temperature food and drink lest cold irritate the vagus nerve. As the plumbing and electrical circuitry interface with the muscle stimulation and perfusion became more well known, treatments became more aggressive – getting patients up and moving right away, reperfusing coronary arteries and stenting them, ablating lesions, etc. Then the focus spotlighted statin use for prevention, concomitant with pharma DTC advertising and KOLs. Only recently has any of this been questioned, and lo and behold, stenting and preventive statin use may not do anything at all in terms of disease prevention.
    Not for nuthin’ has clinical depression been found to coexist and correlate with heightened morbidity and mortality with heart disease.
    Patient stays in critical care units for heart attacks (MIs) went from 7-10 days to 1-2. Of course, patient education, diet teaching, stress management, socioeconomic assessment went out the window. In other words, self management and quality of life factors were ignored and abandoned. Patients are sent home with prescriptions, stents, pacemakers, automatic internal defibrillators and all manner of coronary hardware, and sometimes followup appointments. They are not linked to case managers, community resources and psychosocial supports. They never learn that simple, but profound, diet changes could reverse risk factors and free them of medications, quality of life limiters and discomfort.

    All this history to say that psychiatry has been looking for a solid organ model of pathophysiology to fling itself against and hope it sticks. The “neural circuitry” model combined with interfacing the neurotransmitters model in my view, is where they are aiming. Chemicals and electricity plus the organ itself to ablate, stent and electrically stimulate will generate patients, income from treatments and a shiny veneer of legitimacy, if it succeeds.

    It will leave patients worse off than no treatment at all, but then, patient well-being and beneficence don’t come into play in this agenda.

  2.  
    Talbot
    April 9, 2012 | 9:08 AM
     

    You used to always be able to tell ghost written, pharma funded stuff from legit research because the former had the types of statements you’re calling out here–the blanket “proof” statements from out of nowhere, “now we’ve agreed…” etc.

    I fear that those types of hack-based, opinion for sale statements are now being used by the non-pharma-funded. That that is the new, acceptable style for everyone. If that’s the case, then we are all in deep trouble.

  3.  
    aek
    April 9, 2012 | 1:44 PM
     

    Blogorrhea rumination over this development.

  4.  
    don
    April 9, 2012 | 1:59 PM
     

    That is a powerful last sentence that seems to hit the mark.

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