coffee-house science…

Posted on Tuesday 4 June 2013

Those of us coming into adolescence in the 1950s were too young to be Beatniks, but we knew something about the rules. It was kind of hard work. Go to the coffee house and talk about the really deep things in the universe, expressing unique and novel opinions without being committed to doing anything except keeping the conversation going. And even though you knew you weren’t going to be actually involving yourself, you couldn’t just say that. You actually had to know the topic pretty well so you could say wise things along the way, otherwise, you were labeled as the worst thing imaginable – a pseudo-intellectual. [which was as bad as working at DOW Chemicals]. In the coffee house, you had to know your stuff to go nowhere. After all, the point wasn’t to say or do anything that mattered – but just sound that way. The point was to fit in and keep up with the other unique and clever people at the coffee shop.

We have a lot of coffee house science, particularly in psychiatry – people who take the results of clinical trials [they didn’t design] on patients [they haven’t seen] and give presentations of papers [they didn’t write] that sound wise and novel – fitting into a world that always ends the same way, needs further study. They don’t look like Beatniks, but they play the same game. They’ve stayed in the coffee house for years by knowing the rules about how to stay, but accomplish little of note. There are some prime examples in my recent posts about STAR*D [a whole lot better than this…] or Vortioxetine [way past time…, the squeaky wheel…].

It’s ironic that so many of the unique coffee house scientists are the noisy arm of collaborations. I mentioned a study [coming soon…] that proposes to show that childhood abuse actually changes neuroanatomy which has something to do with the symptoms in later life. While I’m skeptical, I was kind of interested in seeing what their data was. Here’s the abstract:
Decreased Cortical Representation of Genital Somatosensory Field After Childhood Sexual Abuse
by Christine M. Heim, Ph.D. Helen S. Mayberg, M.D. Tanja Mletzko, M.S. Charles B. Nemeroff, M.D., Ph.D. and Jens C. Pruessner, Ph.D.
American Journal of Psychiatry. 2013 170:616–623.

Objective: Sexual dysfunction is a common clinical symptom in women who were victims of childhood sexual abuse. The precise mechanism that mediates this association remains poorly understood. The authors evaluated the relationship between the experience of childhood abuse and neuroplastic thinning of cortical fields, depending on the nature of the abusive experience.
Method: The authors used MRI-based cortical thickness analysis in 51 medically healthy adult women to test whether different forms of childhood abuse were associated with cortical thinning in areas critical to the perception and processing of specific behavior implicated in the type of abuse.
Results: Exposure to childhood sexual abuse was specifically associated with pronounced cortical thinning in the genital representation field of the primary somatosensory cortex. In contrast, emotional abusewas associated with cortical thinning in regions relevant to selfawareness and self-evaluation.
Conclusions: Neural plasticity during development appears to result in cortical adaptation that may shield a child from the sensory processing of the specific abusive experience by altering cortical representation fields in a regionally highly specificmanner. Such plastic reorganization may be protective for the child living under abusive conditions, but it may underlie the development of behavioral problems, such as sexual dysfunction, later in life.

I can’t tell you what their data was because it wasn’t there, at least not in any way an expectable reader of the American Journal of Psychiatry might understand. I’m afraid an expert would be in the same boat. So all I can do is tell you what they did. They recruited 51 women some with abuse histories and some not. With this group, it’s been traditional to recruit from the Grady Hospital [Atlanta Georgia] waiting room or from bus advertisements, but in this paper they don’t say. The women filled out questionnaires about childhood abuse and had structured interviews to rate the extent of the abuse. Structured DSM-IV Interviews provided Psychiatric Diagnosis. They had MRIs ["a high resolution T1 three-dimensional magnetization-prepared rapid gradient echo sequence (TR=2,600 ms, TE=3.02 ms, flip angle=8°, field of view=2563224 mm, in-plane resolution isotropic, 1 mm3)"]. All of this happened in Atlanta, GA, US. Here’s my new hobby – a world map of the study:

The MRI data was processed in Montreal [or Berlin or Miami] to measure cortical thickness:
    Cortical thickness analysis was performed using the automated analyses pipeline developed at the Montreal Neurological Institute. In brief, anatomical MRIs are corrected for nonuniformities, registered into standard stereotaxic space, and classified into gray matter, white matter, and CSF using a neural-net classifier. At the core of the cortical thickness analysis, a constrained Laplacian anatomical segmentation using proximities is applied to determine white and gray matter surface boundaries using a surface deformation algorithm. This procedure computes 40,000 vertices of white and gray matter surfaces that are linked. Cortical thickness is computed as the distance between these linked vertices. In a final step, individual cortical thickness data were smoothed using a blurring kernel of 20 mm.
Any questions? I don’t mean to be quite so facetious as I sound. It’s hard to explain such things or show them in some way that an expectable reader might follow. But what comes next is no more accessible. They run multiple regression analyses on the correlations between the cortical thicknesses so derived and the results of the abuse indices they generated from their questionnaires and structured interviews, holding this and that constant, correcting for that and this. All of these things occur in a black box that we can’t see the inside of on data that’s not shown. What we see are some pictures of brains with color-coded significant correlations from the regressions. The closest we get to tangible data looks something like this:
    "… emotional abuse specifi cally affects the areas of the left (x= -3, y= -61, z=45; F=7.8, p , 0.05) and right (x=6, y= -49, z=51; F=6.2, p , 0.05) precuneus and the left anterior (x= -4, y=40, z=11; F=6.9, p , 0.05) and posterior cingulate cortex (x= -2, y= -47, z=28; F=8.1, p , 0.01). We also observed thinning in the face region of the somatosensory cortex (x= -56, y= -12, z=45; F=22.7, p , 0.001). Hence, emotional abuse, which likely represents experiences of parental rejection and is often considered most detrimental in terms of altered concept of ‘self,’ is associated with the cortical thinning of regions implicated in mediating self-reflection, self-awareness, and first-person perspective."
or this:
    "we investigated the effect of age at onset of any abuse on cortical thickness in the group of women reporting moderate to severe exposure. This analysis revealed that earlier exposure was associated with thinning of the left temporal pole (x= -49, y=22, z= -26; F=19.9, p , 0.001), the left parietal lobe (x= -63, y= -32, z=45; F=18.9, p , 0.001), the left frontal pole (x= -28, y=63, z=12; F=16.8, p , 0.001), and the right frontal pole (x=11, y=69, z=4;F=18.6,p , 0.001), areas associated with autobiographic memory, as well as thinning of the anterior cingulate cortex (x= -2, y=21, z=22; F=8.13, p , 0.01). This finding is concordant with reports that abuse occurring earlier in childhood is often associated with absence of memories concerning the abuse. We did not see an effect of duration of the abuse, which supports the assumption that the observed effects reflect developmental programming rather than consequences of cumulative exposure to maltreatment over time."
Why do I call this coffee house science? These people sit in the coffee house and talk about the results of regressions that we can’t see with  multiple corrections we don’t know about and we are asked to accept the accuracy of the complex methodology and unseen calculations on faith. Worse, based on questionnaires and structured interviews of what concretely happened in the subjects lives, we’re told that these results say something about "experiences of parental rejection"; "altered concept of ‘self’"; "self-reflection, self-awareness, and first-person perspective" with no actual assessment of these parameters in the subjects themselves.

So even if we accept the methodology used to measure cortical thinning at face value and accept that the questionnaires and structured interviews actually give an accurate index of the type and magnitude of the child abuse in the subjects, we’re still left entering the world of multiple regressions with no direct access to any data other that the significance corrected in multiple ways we can’t see. Anyone who has done multiple regressions with large data sets using a statistical package knows that if you play with the data enough, you can make it sing any song. It’s where the saying, "Torture the data long enough, and it will tell you anything you want to hear." And then the authors speculate on complex abstract concepts like "self-reflection" or "parental rejection" without actually assessing these things in the subjects  of the study as if the outcome of a given experience is an index of its impact – a clinically indefensible position. We are supposed to be thinking that the childhood sexual trauma resulted in cortical thinning of the genital sensory area of the brain without asking the subjects about their adult sexual history or experience. If there are subjects with cortical thinning of the clitoral area, are they sexually anesthetic? All of that behind us, we are then teleported into the realm of neuroplasticity, the brain changing anatomically based on experience – a concept on the outer edge of our understanding at best.

So everything said in this study may be absolutely correct or it may all be a fantastic coffee house poetry reading. What’s included in this paper itself doesn’t help us make that distinction. Rather than giving us a narrative we can’t possibly vet on the way to conclusions filled with speculation, how about a scatter-plot of the various trauma indices against the cortical thickness in different parts of the cortex. Maybe we can’t grasp the methodology completely, but we could at least see something concrete that gave us a sense of what we’re being asked to believe.

I’m not sure what part Dr. Nemeroff actually played in this study, but his track record doesn’t support anyone asking us to accept things he publishes on faith alone. There’s too much consistent dodgy science in his former outings to ask us for that – particularly when the conclusion has so many conceptual ramifications. This is the kind of study where the raw data, at least the various values of cortical thickness by cortex area and the results of the associated subject data should be available for validation by some kind of outside source. I can’t imagine how a peer reviewer could evaluate this paper.

Does child abuse change the brain? Haven’t a clue. And I sure don’t know what to say to this:
    Neural plasticity during development appears to result in cortical adaptation that may shield a child from the sensory processing of the specific abusive experience by altering cortical representation fields in a regionally highly specific manner. Such plastic reorganization may be protective for the child living under abusive conditions, but it may underlie the development of behavioral problems, such as sexual dysfunction, later in life.

Update: And then  there’s…
    1. "The Nemeroff case tells us something about how the psychiatric establishment and the biomedicine-driven research world work, and about their relationship with the pharmaceutical industry that has a vested interest in the biologisation of human experience – indeed in the disease – mongering Jonathan Gornall reprises. Nemeroff’s appointment to another chair of psychiatry as if nothing had happened and when the case against him was not closed, his receipt of substantial new grants, and the Institute of Psychiatry in London continuing to laud him as “one of the world’s leading experts”, all show how psychiatric academe sails blithely on as if such revelations beg no broader questions about its associations and supposed scientific independence, about research ethics, and specifically how conflicts of interest must inevitably contaminate the integrity of the research data informing publications in the scientific literature."

      "It is worth adding that in fact no clinically meaningful “neurobiology of depression” has been discovered- and perhaps never will be, given that “depression” is merely a syndromal category, subsuming a very heterogeneous range of patients and circumstances,and whose widely differing understandings of their distress point rather more often to social space than to the space between their ears."

  1.  
    June 5, 2013 | 12:23 AM
     

    Even if we accept all of their methodology and results, the conclusion is just so odd…they could just as easily have said that abuse was “neurotoxic” to certain sensory areas rather than acting as a “shield” or being “protective” of anything.

  2.  
    wiley
    June 5, 2013 | 12:26 AM
     

    Well. Let’s just say that it doesn’t surprise me at all that a bunch of bio-neuro-psychiatrists look at women’s brains and see female genitalia.

  3.  
    June 5, 2013 | 12:31 AM
     

    Psycritic,
    Right. Or just shown their findings and skipped speculating altogether. The finding alone would be a big deal all by itself…

  4.  
    Stan
    June 5, 2013 | 12:35 AM
     

    Biological Psychiatry is pretty much summed up in one simple catch phrase: “psycho-babble”

  5.  
    Speck
    June 5, 2013 | 1:59 AM
     

    “I can’t imagine how a peer reviewer could evaluate this paper.”
    That’s a good point… we don’t wonder why some of this stuff got published.

    Sadly, a manuscript will usually get published without much if any review process if the author already has a high standing, e.g. ‘is popular’. This is huge problem in all fields of science unfortunately.

    This is what the peer reviewers face in psychiatry journals, and probably much worse in neuroscience:

    “Common statistical and research design problems in manuscripts submitted to high-impact psychiatry journals: what editors and reviewers want authors to know.”
    http://www.ncbi.nlm.nih.gov/pubmed/19435635

    The most commonly cited problems regarded failure to map statistical models onto research questions, improper handling of missing data, not controlling for multiple comparisons, not understanding the difference between equivalence and difference trials, and poor controls in quasi-experimental designs.”

    Any of that sound familiar?

  6.  
    June 5, 2013 | 2:24 AM
     

    So neuorplasticity is the problem in the case of child abuse?

    The same neuroplasticity that’s otherwise ignored when it comes to PTSD, severe “mental illness”?

    That neuroplasticity?

    Where do these people come from?
    Any chance we can send them back to their own planet?
    I’m just askin’…

    Duane

  7.  
    June 5, 2013 | 2:30 AM
     

    I’m not a doctor, but I thought the term was ‘neuroplasticity’, not neural plasticity.

    http://www.medterms.com/script/main/art.asp?articlekey=40362

    Oh well, who knows?
    Like all of this stuff, who really knows?

    Duane

  8.  
    Berit Bryn-Jensen
    June 5, 2013 | 3:05 AM
     

    They recruited 51 – fiftyone – women, and make sweeping statements about brains, neuroplasticity etc based on this minimal number of female research objects, with and without abuse histories… I second Peanuts. Good grief!

  9.  
    June 5, 2013 | 3:26 AM
     

    Or ‘Good Melancholia’
    Or ‘Good Major Depressive Disorder’

    Whatever the politically correct term is supposed to be.
    I forget.

    Duane

  10.  
    beatnik
    June 5, 2013 | 10:07 AM
     

    You offer a low hung moon,
    reaching only a bare twig
    that waits a fragile moment
    to snap it into a final tumble
    then like its leaves lying
    thin laced at the tree root,
    it too will turn to dust
    and tomorrow will be its wasted dream.

    Give to me something more.
    Something not of fantasy
    like some shiny star
    dancing perpetual pirouettes
    for a trembling daisy
    with not a choice
    but to wait winter frost.

    Bring me not a field
    laden with tall grass
    waving its magnificence
    soon to wilt in a summer rain.

    Give to me a poem
    which you find insignificant
    in your world of spurious adornments
    and i will place a halo
    about the heads of men.
    I will disintegrate
    books of hate and veils of truth.

    One poem – titanic in performance –
    and your offerings will seem
    but a mere – low
    hung
    moon.
    * * *

    jau billera

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