The diagnostic crisis in child psychiatry

The diagnostic crisis in child psychiatryThanks to Mickey for his perspective on the chaos in diagnosis in child psychiatry, described in yesterday’s New York Times. (What’s Wrong with a Child? Psychiatrists Often Disagree):
At a time when increasing numbers of children are being treated for psychiatric problems, naming those problems remains more an art than a science. Doctors often disagree about what is wrong.

A child’’s problems are now routinely given two or more diagnoses at the same time, like attention deficit and bipolar disorders. And parents of disruptive children in particular — those who once might have been called delinquents, or simply “problem children” –— say they hear an alphabet soup of labels that seem to change as often as a child’s shoe size.

Psychiatrists have no blood tests or brain scans to diagnose mental disorders. They have to make judgments, based on interviews and checklists of symptoms. And unlike most adults, young children are often unable or unwilling to talk about their symptoms, leaving doctors to rely on observation and information from parents and teachers.

““Psychiatry has made great strides in helping kids manage mental illness, particularly moderate conditions, but the system of diagnosis is still 200 to 300 years behind other branches of medicine,”” said Dr. E. Jane Costello, a professor of psychiatry and behavioral sciences at Duke University. “On an individual level, for many parents and families, the experience can be a disaster; we must say that.”

The main problem is that these diagnostic labels are findings, not diseases. A good example of this problem is attention deficit disorder, which in many families seems due to a single autosomal dominant gene. Despite this genetic simplicity, people with attention deficit disorder typically have other disorders too, including oppositional defiant disorder, conduct disorders, as well as affective, anxiety, learning disorders and even poor handwriting. This is not surprising – being overwhelmed with sensory input, as occurs in attention deficit disorder, could easily produce these multiple symptoms.

All these labels are based primarily on symptom checklists. According to the American Psychiatric Association’s diagnostic manual, for instance, childhood problems qualify as oppositional defiant disorder if the child exhibits at least four of eight behavior patterns, including “often loses temper,” ““often argues with adults,”” ““is often touchy or easily annoyed by others” and ““is often spiteful or vindictive.”

Dr. Darrel Regier of the American Psychiatric Association, who is coordinating work on the next edition of the associationՉ۪s diagnostic manual for mental disorders, due out in 2011, said that researchers would focus on drawing distinctions among several childhood disorders, including bipolar disorder and attention deficit disorder.

““We wouldn’t disagree that criteria for these disorders currently overlap to some degree,” Dr. Regier wrote in an e-mail message, “and that a significant amount of research is under way to disentangle the disorders in order to support more specific treatment indications.”

The Chinese Restaurant Menu approach used in the diagnostic manual is part of the problem since it combines rigidity and ignorance. A statistical pattern matching approach would be an improvement, but major progress will require new knowledge. Once we start to make progress the pace of advances will increase: once we have gene tests for a few diseases, progress in other diseases will also accelerate since the bin of undiagnosed patients will become simpler.

From which disease will the first advances come? Attention deficit disorder should be an early success because it often has such simple inheritance. Why don’t we have an attention deficit disorder gene yet? One difficulty may be that many single genes can cause attention deficit disorder and this heterogeneity on a population level messes up positional cloning studies. Another problem is that it can be difficult to make the diagnosis of attention deficit disorder in females, leading to data too messy for positional cloning studies.

If genetic heterogeneity is the problem a more promising strategy may be to test candidate genes in small families in which all patients share the same problem gene. This can work if you understand the biology, but since the presumption that dopamine transmission problems underlie attention deficit disorder has not borne fruit it would not be surprising if a dopamine disorder is the wrong hypothesis.

It sounds like we are in a rut, but there are enough MDs with basic science experience floating around and the cost of sequencing a gene is getting so low that someone is going to hit the bulls-eye with a good hunch on a different candidate gene.

November 12, 2006

3 thoughts on “The diagnostic crisis in child psychiatry”

  1. My issue is Zyprexa which is only FDA approved for schizophrenia (.5-1% of pop) and some bipolar (2% pop) and then an even smaller percentage of theses two groups.
    So how does Zyprexa get to be the 7th largest drug sale in the world?

    Eli Lilly is in deep trouble for using their drug reps to ‘encourage’ doctors to write zyprexa for non-FDA approved ‘off label’ uses.

    The drug causes increased diabetes risk,and medicare picks up all the expensive fallout.There are now 7 states (and counting) going after Lilly for fraud and restitution.

    Daniel Haszard

  2. I find Krause et al’s research on DAT sites using SPECT imaging to be rather interesting in this regard:

    This and several other studies have found that ADHD patients have increased striatal DAT densities in exactly the frontal and prefrontal regions where you would expect given the executive dysfunction presented by the disorder.

    Unfortunately, from what I hear, the DAT-10 allele, which showed promise, doesn’t seem to be panning out as a likely candidate gene, although I’ve heard good things about DRD-4.

    The hypothesis of multiple possible causative mutations makes a certain amount of sense, given that the disorder can be found on every continent and every ethnic/racial phenotype, as well as possibly explaining the subtle differences between ADHD-I, ADHD-HI, and ADHD-C, while the hypothesis that only one of these mutations is sufficient to result in the disorder would explain the exceptionally high hereditary correlation.

    Unfortunately yeah, this makes it ten times more difficult to pinpoint the genes involved. The only thing that could make this disorder more of a political football is if we wind up finding one gene for Ashkenazi Jews, three genes for Europeans, five genes for sub-Saharan Africans, three genes for central Asians and Indians, and two genes for Northeast and Southeast Asians.

    And then it raises an even scarier question: Suppose that only some, but not all genes are identified. Could an insurance company use the fact that a patient has tested negative for the known alleles as an excuse to deny payment for ADHD meds? (since certain insurance companies will do anything possible, including lying about FDA approval, to avoid covering ADHD meds)

  3. There’s also the point that if you’ve missed the “real” problem, it’s liable to look like borderline signs of a half-dozen other problems. I have personal experience here; besides my known ADHD and hearing loss, I was considered throughought my school years to have an assortment of “miscellaneous” LD problems. Only recently did I discover Non-Verbal Learning Disorder, which was just being defined when I was in high school — and which neatly explains all those “miscellaneous” issues.

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