ADHD World

Diagnosis in ADHD: Problems and Solutions

2011-03-27T14:43:00.003-04:00

DIAGNOSIS IN ADHD: PROBLEMS AND SOLUTIONS
C. Keith Conners, Ph.D.
Presentation to the Ontario Psychiatric Society Toronto, Ontario, Canada April 16, 2011

Diagnosis in ADHD has had a rocky history. One only has to recall the events occurring at the NIMH Consensus Conference on ADHD in 1998. When asked his opinion about diagnosis, Mark Vonnegut, one of the experts on the panel, commented that “Diagnosis in ADHD is a mess.” This answer was reprinted in headlines the next day in newspapers around the world. When asked how you make the diagnosis, Dr. Vonnegut, threw up his hands, then took a line from Supreme Court justice Potter Stuart. The United States Supreme Court was in the midst of a controversy on how to define pornography. When asked for his definition , Justice Stuart replied, “I don’t know how to define it, but I recognize it when I see it.”

Dr. Vonnegut was probably correct in assuming that a fly-by- the-seat-of-your-pants recognition-of-ADHD-when-you-see-it, is the approach of most medical practitioners. Surveys of diagnosis in practice have repeatedly shown that many practitioners fail to follow the explicit guidelines for diagnosis,(1)such as those proposed by the American Academy of Pediatrics(2). This has led to repeated findings of over-diagnosis, based on the actual figures of ADHD from epidemiologic studies. (3) The late Atilla Turgay had developed similar guidelines for the Canadian Psychiatric Association, so we can assume that this audience will surely be familiar with those guidelines.

But there are other problems in making the diagnosis than simply ignoring or being unfamiliar with the guidelines. One major problem has to do with the criterion requiring impairment in at least two different settings. In early trials of DSM it was found that by using impairment in only one site, such as school or home, there was an excess of diagnosis, rising to as much as 40% of the normal population. Since most psychiatrists rely solely on the report of a parent about the child’s school behavior as well as their home behavior, the school setting is only indirectly being assessed. Mark Wolraich has reported that failure to get school information was one of the major limitations of diagnosis among pediatricians; and the evidence-based guidelines stress the importance of direct reports from classroom teachers.(4)

Another major challenge with diagnosis is the presence of comorbidities. Comorbidity with ADHD is not like seeing a diabetic who also has a broken leg, where the comorbid symptom is assumed to be caused independently from the diabetes. With ADHD two thirds of cases will have some associated problem with oppositional, conduct, anxiety, or depressive symptoms. These more “complicated cases” are the rule rather than the exception, so it places the burden on the diagnostician to have a good knowledge of the comorbid conditions. Factoring those comorbidities into the treatment plan is essential for knowing the type and sequence of appropriate treatments.

Many parents will show up at their first interview ready with an internet-based diagnosis that includes a wealth of behaviors that may or may not be relevant to ADHD. Like Mark Twain, after reading a medical text book and finding that he had “every malady except housemaid’s knee,” parents and young adults who have read “Driven to Distraction,” will allege symptoms covering all of the DSM disorders. Which ones rise to the level of a true comorbid disorder, which are significant but below the diagnostic threshold, and which are simply factitious provides a diagnostic challenge.

Finally, there is a special problem in making diagnoses for very young children. Many believe that such a practice is harmful to the child and family by providing an early stereotype that inflicts damage to self esteem, while others believe that such diagnoses are unreliable or unwarranted because of rapid developmental changes, which obscure meaningful diagnosis in preschoolers and younger children.

So, in summary, we see problems in ignoring evidence-based guidelines, problems in defining the pervasiveness of impairments, problems with the comorbid or associated conditions of ADHD, and problems in applying adult-based criteria to younger children. What resources are available to help with the problems we have identified here? Here is where my personal experience may be relevant. Permit me to recount a little of my own history in trying to deal with these problems.

When I began my first job at Johns Hopkins Medical Center in 1960, I was asked by my boss, Leon Eisenberg, to analyze the data from his just-completed randomized trial of Dexedrine and placebo in “delinquent” boys living in a cottage home run by social services.(5) The data I had to work with was a checklist of symptoms taken from Leo Kanner’s textbook of child psychiatry. The items in the checklist were simply being summed to give an overall symptom score. The data were striking in showing a dose-related improvement from the ratings done by the cottage “parents.” I became interested in the problem of monitoring drug effects with the checklist, and decided to convert it into a scale by having each of the 93 symptoms rated from 0-3, or “not at all, just a little, quite a bit, and very much.” Later I did a similar revision with a 39-item teacher report.

By factor analyzing (that is, clustering) the items according to their associations with each other, I was able to identify a small number of symptom clusters that were reliable and appeared to reflect some basic dimensions of behavior in our outpatient clientele. I began to collect normative data from children attending our clinic.

In later years, with the help of MHS here in Toronto, we were able to obtain a national database from thousands of children in North America and Canada. At that point we were able to develop normative data for separate ages and gender, along with other demographic data. So now we had a scale for measuring the position of any putative ADHD patient compared with the average child of the same age and gender in the population. Very early in the use of these scales I noticed a lot of pressure from respondents to have shorter scales, so I eventually developed a 48-item parent scale, and by taking the best items from there I was able to create a 10-item scale. We called it the “hyperactivity index” because it seemed to reflect the essential characteristics of the hyperkinetic child; it was especially favored by teachers who resisted the longer forms.

In pursuit of even greater brevity, I once dreamed I had found a one-item scale, but when I woke up I forgot what it was. (This joke somewhat reminds me of the true story of William James when he was taking nitrous oxide, during which he felt he could discover the greatest secret of the universe. When he awoke from his drug-induced insight he finally remembered it well enough to write it down: “Higgedly hogamous, woman is monogamous; hoggedly higamous, man is polygamous.” He was disappointed, though some believe he may have hit upon an eternal truth.) But I digress.

We still use the original 10-item index because it seems to be a very sensitive indicator of response to drugs or other treatments, particularly when trying to adjust dosage for an individual, or to track behavior over time. But needless to say such a brief scale cannot cover the scope of information required for diagnosis or initial assessments. Because of the complexity involved in ADHD diagnosis, the trend towards brevity has been reversed, as greater precision and clearer guidelines are needed for a comprehensive evaluation that includes differential diagnosis, measures of impairment, and much other relevant information. That is why our latest diagnostic aide for ADHD (the C-3), covers ADHD as well as its major comorbid conditions of ODD, CD, Anxiety, and Depression. The companion scale to the C-3 is a much more detailed scale of all the major pathologies identified by DSM in childhood, called the “CBRS”, or Comprehensive Behavior Rating Scale. Let me give you a brief overview of our reasoning and the process behind the development of these two major rating scales.

First, we had at hand a large body of data from previous studies, such as the national survey of major rating scales carried out by Tom Achenbach, Herb Quay, and myself, funded by grants from the American Psychological Association.(6) This survey identified eleven major clusters of symptoms that cut across all socio-economic and ethnic levels. Second, we had the symptoms and impairments identified by DSM-IV for major childhood disorders.

We pooled all of this information and set about culling the data for redundancies, removing items of very low frequency, un-readability; and translations for the Spanish version carefully adjusted for the cultural meaning of the items. This pool of items was submitted to various experts in the field for suggestions, omissions, and relevance. On a test sample we performed several Exploratory Factor Analyses of the data, finally creating a “model” structure which was then verified by a Confirmatory factor analysis from a large North American national sample.

(Now I recognize that psychiatrists’ eyes tend to glaze over when psychologists start talking about factor analyses, but as in Herman Hesse’s novel, The Glass Bead Game, we have to have our own priestly mysteries, that we indulge in for our own special version of reality. This is a version of reality which sees that underlying the multiform appearances of behaviors there is a causal structure which we can identify by looking for the orthogonal relationships among groups of symptoms or behaviors).

Note that there are two parallel sets of “diagnoses” in these results: one of course is just the diagnoses representing the DSM-IV categories, albeit simplified in language and re-worked to be readable and comprehensible to parents, teachers and patients, and converted into normative scales. These are the “rational diagnostic categories,” only partly based on empirical data as well as clinical acumen acquired over several decades. The other set of content scales are those empirical factors which emerge from the factor analyses, and although they overlap with DSM, they empirically identify broad patterns.

In practice, the psychiatrist constructing the diagnoses of a patient will certainly want to use the “official” DSM categories, for medico-legal and professional communications, and the rating scales add a considerable benefit over the short paragraphs from the DSM handbook: Each diagnostic category is normed against a national sample adjusted for age and gender across a census-based representative population. So the prevalence of any given diagnosis in the population allows the clinician to know where the patient falls in the statistical distribution. While somewhat arbitrary, we set a threshold of 1.5 standard deviations above the mean as a clinically meaningful cutoff point for each score, including those from parents, teachers, and self-report of the child.

Alternatively, the scoring for the DSM categories can be done exactly as required by DSM involving the number of symptoms, rather than the statistical distribution in the general population. For the empirical or content scales, which overlap the DSM scales, we have clusters of symptoms that “appear in nature,” not just those constructed from closed-door committee meetings of the DSM working groups. We also calculated an overall statistical index of the probability that the patient has a diagnosis, based upon a comparison of a large well-identified clinical sample with matched normal controls. This allows the clinician to have an empirically derived probability estimate that the patient lies within the range of previously diagnosed patients who had a full clinical workup.

Built into the scales is also a check on the reliability of the informant, based upon overly negative or overly positive reporting biases, and consistency of response. The specifics of the scales and the steps needed to interpret them are provided in a Quick Reference handout. Speaking of one’s eyes glazing over, try to score these scales by hand, consisting of hundreds of items, validity checks, content scales, symptom scales, impairment items, and a variety of other clinical and immediate action scales, for parents, teachers and self-report by the patient. No wonder Mark Vonnegut elected to just wait until he saw it, instead of all that bother. Well, thanks to modern technology, the burden of all that work lands squarely on the parents, teachers, and patients who fill out the scales, not the psychiatrist who has to interpret them. The scales can be scored electronically on- line or a software disc, resulting in a beautiful comprehensive report, complete with graphs and interpretive results. Results from teachers and parents can be obtained directly from their computer-based input, with the scored results and interpretive reports available directly to the clinician.

Regarding early childhood diagnoses, recent epidemiological studies have shown that valid and reliable DSM diagnoses can be made in preschoolers(7) and an early childhood subcommittee of the APA has developed a modified diagnostic algorhythm for preschoolers to deal with constructs derived from older children or young adults. (4) I have provided an overview of those studies, which is available on my blog at http://adhd-world.blogspot.com/. We recently published an Early Childhood Diagnostic and Developmental Scale which seeks to identify the major symptom patterns in preschoolers and younger children, along with a parallel set of items to identify the major childhood developmental issues. The Conners Early Childhood™ (Conners EC™) aids in the early identification of behavior, social, and emotional problems in preschool-aged children 2 to 6. It also measures whether or not a child is appropriately meeting major developmental milestones. This scale, like our others, is described on the MHS website at MHS.com/Conners.

Finally, how should one use these reports in making a diagnosis? Let us stipulate that the most essential ingredient in making the diagnosis of ADHD is a wise and experienced clinician, trained broadly in the medical arts, particularly in taking a history; and one who is practiced at gathering as much information about the patient as is practical within the time limits of the particular setting, the availability of informants, and reimbursement issues. The key ingredient in all of this is the skillful history by the clinician, which then allows him or her to formulate hypotheses about the clinical status of the patient. The rating scale results are only hypotheses to assist clinicians in making the final decisions, based upon their own hypotheses gained from a careful and comprehensive history, including the family psychiatric history, medical examination (for example to rule out the rare thyroid condition), family functioning, educational history, and a host of possible environmental contributions. But we believe that the rating scales add a solid empirical basis to the entire process, addressing the issues we outlined in the beginning: following the best-practice guidelines, dealing with comorbidities, addressing areas of impairment, and assessing very young children.

In summary, we started with quite a few useful items to measure treatment outcome. Then we progressed to a smaller set of items by refining the long original list. And finally we ended up with a much more comprehensive set of rating scales in response to the obvious need to cover a very large field of pathologies and diagnoses. This approach, which started long ago, and evolved over time, represents my approach to diagnosis with ADHD. I think that the rating scale tools are extremely helpful in assisting the clinician in dealing with the diagnostic challenges we have discussed.

But of course, helpful as these tools are as aids to the practical problem of making a diagnosis according to today’s guidelines, they do not deal with the fundamental problem, that there is no patho-physiological diagnosis. Etiological diagnoses in psychiatry have largely been abandoned because of the absence of a patho-physiologic or anatomic causal basis, in favor of DSM’s strictly behavioral and clinical approach. So where do we go from here with diagnosis of ADHD? I have heard that psychiatrists like to talk about dreams, (at least they used to; but perhaps they mostly talk about pills now); but I will tell you one of mine. I call this dream, “A revised personal history of my work on diagnosis: or a Path Not Taken”.
This dream appears to be a wish-fulfillment about how I might better have spent my time. In the first part of this dream it is 1911, and a few friends of mine (Marie Curie, Henre Poincare, Albert Einstein, and Max Planck are at the Solvay Conference in Brussels, standing around endlessly discussing particle physics and such, and I am wondering why they aren't paying attention to ADHD, since Sir George Still had only recently identified (in 1902) a group of children we now call ADHD. (Now I know you are wondering why I, who was born in 1933, could know this; but obviously in psychoanalysis we know that time travels very peculiarly in dreams.

Later in this dream it is 1960, and I have just started work at Johns Hopkins. Two years later one of my great heroes, Rachel Carson, published Silent Spring. She tells me that “From 1945 when the use of synthetic pesticides began in the United States, to the time Silent Spring was published, pesticide use increased about sixfold. In the ten years between the publication of Silent Spring and the banning of DDT in 1972, pesticide use increased tenfold, to about one billion pounds annually".

Since then the total quantity of pesticides in terms of pounds has not increased; however, the actual toxicity of pesticides has increased ten to twenty times. (8) Figures from today estimate that less than 0.01 percent of the pesticides that are applied reach the target pests, which means that 99.99 percent of the pesticides that are applied pollutes the environment. About 35 percent of the food that is purchased has measurable levels of pesticide residues, with 1 to 3 percent having residues that are above accepted tolerance levels.

Knowing all these facts in 1962, I began my scientific career in search of a physical pathology for ADHD (hyperkinesis, MBD, whatever) that would provide a true patho-physiologic bases for diagnosis. So what I did (in the dream) was the following: I never liked animal studies but knew it was essential to this program, so I studied the toxic effects of pesticides on animal behavior, and then showed by histo-pathological brain studies that the pesticides not only destroyed three of the dopamine receptor sites, but did so by transmission through the breast milk and amniotic fluid of the mother rats.

I also discovered that these toxic organophosphates worked to destroy acetyl cholinesterase, leaving acetylcholine nerve fibers in a constant state of excitability. It was then an easy step to human studies, where the concentrations of pesticides in different areas of the country were easily matched to prevalence levels of ADHD in pregnant mothers and in their offspring. The follow-up studies of the offspring showed conclusively that ADHD was tightly linked to levels of pesticides in the mothers and the child at birth.

Then, by analyzing organophosphate exposure in the urine of more than 1,100 children 8 to 15 years old, I found that those with highest levels of dialkyl phosphates which are the breakdown products of organophosphate pesticides also had the highest incidence of ADHD. (You might notice the suspicious similarity of my results to those of Bouchard, et al, just last year). Overall there was a 35% increase in the odds of developing ADHD with every 10-fold increase in urinary concentration of the pesticide residues. The effect was seen even at the low end of exposure: children who had any detectable, above-average level of pesticide metabolite in their urine were twice as likely as those with undetectable levels, to show symptoms of ADHD. (8)

With the aid of Russel Schachar and his group we were then able to relate particular endophenotypes of ADHD to organophosphates, accounting for the fact that there is a high rate of genetic loading in ADHD, and the fact that a certain proportion of pesticide exposures do not result in illness. The fact that about 300,000 humans are poisoned with pesticides annually in the United States, and about 26 million poisoned worldwide, leaves us with no doubt that ADHD and learning disabilities are but one of the many diseases caused by over use of pesticides.

Finally, the part of the dream which earned me the Nobel Prize for medicine came after I developed a simple blood test for recognizing critical levels of pesticides, and a chemical anti-toxin that cured patients of ADHD. Now that’s what I call a good diagnosis!

Rachel Carson taught us that pesticides “reach through the natural ecosystem, affecting not just the ‘target species,’ but humans and the animals in which we rejoice and the habitats on which our lives depend. Their effects reach not only across the land, but through time into future generations; toxins flow into eggs, through amniotic fluid and breast milk, into the tissues of developing children and the young of other species. The interdependence of life links us inextricably to the death-dealing effects of toxins.”(9)

As my mentor Leon Eisenberg once said, “Perhaps it’s time to worry less about how to describe the bodies we are trying to pull from the river, and see who is pushing them in upstream.”

References

1. Le Fever G, Arcona A, Antonuccio D. ADHD among American schoolchildren: Evidence of overdiagnosis and overuse of medication. Scientific reviews of mental health practice. 2003;2(1).

2. American Academy of Pediatrics: Committee on quality improvement soa-dhdCPG. Diagnosis and Evaluation of the child with ADHD. Pediatrics. 2000;105(5).

3. Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry. Research Support, U.S. Gov't, P.H.S.]. 2003 Aug;60(8):837-44.

4. Carlat H, Perrin J, Stein M. The child with ADHD: Using the AAP Clinical Practice Guideline. American Family Physician. 2001 63(9):1803-11.

5. Eisenberg L, Lachman R, Molling P, Lachner A, Mizelle J, Conners CK. A psychopharmacologic experiment in a training school for delinquent boys. American Journal of Orthopsychiatry. 1963;33:431-47.

6. Achenbach TM, Howell CT, Quay HC, Conners CK. National survey of problems and competencies among four- to sixteen-year-olds: Parents' reports for normative and clinical samples. Monographs of the Society for Research in Child Development. 1991;56(3)[225],):1991.

7. Egger HL, Angold A. Common emotional and behavioral disorders in preschool children: presentation, nosology, and epidemiology. J Child Psychol Psychiatry. [Review]. 2006 Mar-Apr;47(3-4):313-37.

8. Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG. Attention-Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides. Pediatrics. 2010 May 17, 2010:peds.2009-3058.

9. Sideris L, Moore K, editors. Rachel Carson: Legacy and Challenge. New York: State University of New York Press; 2008.

ASSESSING EMOTIONAL AND BEHAVIORAL PROBLEMS IN PRESCHOOLERS

2010-02-22T13:28:00.034-05:00

ASSESSING EMOTIONAL AND BEHAVIORAL DISORDERS IN PRESCHOOL CHILDREN Clinical Presentation, Classification, and Epidemiology C. Keith Conners, Ph.D. Professor Emeritus Duke University Medical Center Presented at the annual meeting of the National Association of School Psychologists Chicago, Illinois, March 3, 2010 Introduction Once again it is a privilege to address this audience of committed professionals who work on the front lines, who bring their knowledge and skills to children who manifest the entire spectrum of mental, emotional, and behavioral handicaps. It is a particular pleasure to be able to introduce some new tools to aid in the understanding of the most vulnerable children of all, those just beginning their journey into the hazards of this world, the preschoolers. I am fortunate to have two experienced and brilliant young colleagues to help present our latest work--Elizabeth Sparrow and Jenny Pitkanen--who will provide you with an in-depth briefing on a somewhat ambitious and comprehensive assessment package, our Early Childhood symptom and developmental scales. [SLIDE 1] My task in this workshop is to provide the background of research and the conceptual basis for the way the scales were constructed. We started with the premise that mental illness is intimately related to the stages of normal development, so that assessment must establish both the features of illness as well as the developmental proficiencies and limitations of the child. Aims of this Talk In line with my Zen approach to workshops, I have made a vow to avoid that dread affliction known as “Death from Powerpoint.” So I will keep slides to a minimum. Much of what I will say is extensively reviewed in a paper by Helen Egger and Adrian Angold [1 ] with over 300 references. I am indebted to Professor Angold, head of the Child Epidemiology Program at Duke, for supplying some of the key slides from his paper. Many years ago George Miller published one of the most famous articles in psychology, which became known as Miller’s Law: “The Magical Number Seven, Plus or Minus Two.” Most people can remember about 7 items without practice, with a confidence band of about 2 items; so 5 to 9 items are reliably retained by the average adult. But being mindful that the attention span of the average adult may be greatly exaggerated, let’s be conservative; I only want you to remember 3 things from this talk. [SLIDE ] But these claims are not without controversy. Imagine that you are sitting in a meeting with your fellow psychologists, or a principal, or some administrators from downtown. (I imagine you have many of those). Or perhaps you are in one of the many IEP meetings, which might include parents, teachers, lawyers or other mental health professionals. Suppose you have decided to do an assessment of the preschooler in question, but there is an outcry against you: “How can you think of doing such a thing? How dare you presume to apply psychiatric syndromes or labels to preschoolers, as if they were the same as older children or adolescents or adults?” After all, look what happened to the last guy who claimed that preschoolers could be diagnosed:] [SLIDE Now, I am convinced that evidence supports those three claims I have listed above; but it is important that you become convinced, in order that you can defend your role as an expert who is assessing a preschooler, without harm to your person or reputation. It is not enough for you to say that you heard me say it at a workshop; you should become familiar with the evidence supporting those claims of preschooler psychopathology. Generally there are only five arguments against labeling, diagnosing, classifying, “medicalizing” or alleging some mental illness in preschoolers: [SLIDE ] (1) Individual differences in temperament in normal development will be inappropriately identified as psychiatric symptoms or disorders. The argument of normal variations in temperament (2) Preschool age involves such rapid physical, neural, behavioral, emotional and cognitive development that it is not possible to identify valid symptoms or clusters of symptoms that can be reliably measured. The argument of rapid, variable, unstable developmental changes. (3) That the dominant psychiatric classification system, DSM, does not take into account developmental variation. The argument that DSM is based solely on adults and older children and there is no continuity of illness from early childhood to adolescence or adulthood. (4) That a young child will be inappropriately ‘labeled’ with ‘diseases’ that will adversely affect self-perceptions or perceptions by others of the child. The argument that labeling creates harmful stereotypes. (5) That problem emotions or behavior are not located in the child but rather in the relationships between parents and children and the wider environment. The argument that mental illness is caused by the context in which the child grows. Temperament and Symptom Cutoff Scores Let’s examine the first claim, that problems might just be normal variations of temperament. Over several decades now, numerous studies have used checklists and cut-points on symptom scales showing many symptoms with high prevalence (7% to 25%) in preschoolers. Evidence shows these to be stable characteristics that can be reliably measured. Many studies consistently validate a major class of ‘externalizing’ as well as ‘internalizing’ syndromes that map onto the broad and specific DSM diagnostic categories. Twin studies demonstrate the heritability of many of these syndromes. Temperament studies do in fact reveal that certain extreme temperament types such as behavioral inhibition and behavioral disinhibition are risk factors for the later development of psychiatric disorders, as well as being associated with problem behaviors in preschoolers. For example, preschool children who respond to negative mood induction by overly-expressive or under-expressive facial response have more anxiety and depression at follow-up in the first grade [2]. Negative emotions of fear, anger, frustration, poor adaptability and high emotional intensity are predictors of later internalizing and externalizing symptoms, as well as antisocial behavior in adulthood. Some studies also link negative affectivity to later anxiety and depression [2 ]. It is true, then, that temperament extremes among preschoolers are linked to significant later psychopathology. However, there are many syndromes that temperament concepts do not cover, and so cannot serve as a sufficient conceptual framework. There is no contradiction in recognizing that there are normal dimensions of behavior, such as activity level, or social withdrawal, or impulsive action, and that one can establish cut-points at which these normal behaviors shade into pathological extremes. In the same way that we set certain extremes of blood pressure as causing pathology, we can establish a category of temperament beyond which bad things result. Thus, a category such as extreme activity level is no longer a harmless normal variation; shyness is a normal temperamental trait, but extreme social withdrawal leads to significant impairment and maps on to the DSM categories we recognize in older children and adults. The key finding in the temperament research has been that extremes at either end of a dimension of temperament, such as activity level or social involvement, are associated with recognizable syndromes at the preschool level, and are predictive of later symptom categories and significant level of impairment. CATEGORICAL DIAGNOSIS IN PRESCHOOLERS: RELIABILITY AND VALIDITY. A carefully developed DSM psychiatric interview showed excellent reliability in a large epidemiologic study [3]. Now the second argument against early diagnosis, that DSM included little direct mention of preschoolers is true; but the American Academy of Child and Adolescent Psychiatry formed a Task Force on preschoolers which produced a modified version of DSM. It is available to you online at: http://www.infantinstitute.org. The modifications adhere as closely as possible to the original DSM-4 criteria but with modifications that take into account the developmental status of the child. For example, consider the category of Conduct Disorder as presented by the Task Force: Conduct Disorder Diagnostic Features Conduct disorder is characterized by a repetitive and persistent pattern of behavior that violates norms and rules and the basic rights of others. The diagnosis of CD rests on the assumption that a child knowingly violates rules, a supposition that requires both knowledge of the rules and intent to break them. Most preschool children are generally able to understand the concept of rules and can control their behavior accordingly. The duration requirement was shortened from 12 months to 6 months. This decision was made because 12 months is a disproportionate amount of a child’s life span in this population relative to older children. Because preschoolers are not skilled in verbal negotiation, they may make threats (e.g., I won’t be your friend) as a means of resolving disputes. Bullying and threatening should be endorsed positively only when threats and intimidation are persistent patterns of behavior and involve threats of aggression or cruelty (e.g., social ostracism) Infrequent, reactive mild aggression towards peers or objects is common during this period. Atypical aggression is more frequent and may be severe (e.g., kicking, biting, and choking). The effect of physical constraints on the manifestation of symptoms during this period must be considered. For example, most preschool children are not likely to have access to firearms or knives, but may use rocks or sticks to hurt someone. Six of the 15 DSM-IV symptoms were modified and 5 symptoms were not. Four DSM-IV symptoms were deleted because they were inappropriate in relation to the developmental capacities of this age group (A10 “broken into someone else’s house, building, or car”; A13 “stays out at night”; A14 “run away”; and A15 “truant”). Since only 1 new symptom was added, this makes fewer possible symptoms available for children to meet the diagnosis. In the task force document a complete table of the empirical studies supporting the categories of psychopathology in preschoolers and infants is presented, including Reliability, Face validity, Descriptive validity, Predictive validity, and Construct validity. The figures for all of the diagnostic categories are very similar to data in older children and adults. So despite the rapid developmental changes taking place in preschoolers, there is good evidence that assessment is both reliable and valid for most of the types of mental illness found in older children and adults. RESEARCH ON DIAGNOSIS IN PRESCHOOLERS: EPIDEMIOLOGY There are four large scale studies documenting the reliability and validity of preschool diagnostic categories. For example, here is the method used in the Egger and Angold study, which used a DSM-based structured psychiatric interview (the PAPA, or Preschool Age Parent Assessment): [SLIDE ] The prevalence of disorders meeting DSM diagnostic criteria in these studies is similar to the prevalence found in older children and adults: [SLIDE ] It is important to note that pediatricians in private practice have been shown to considerably underestimate the percentage of their patients with emotional and mental disorders [5] The comorbidity with other disorders is also approximately the same as data from older children and adults: [SLIDE ] ADHD, its comorbidities, and levels of impairment were found to be highly similar in preschool and school age children by Wilens, et al. [4] An interesting finding in the Egger and Angold study, since replicated in other studies, is that although there appears to be associations among all of the comorbid factors, when the effects of each disorder on all other disorders are controlled for simultaneously, it turns out that the apparent associations between some pairs of disorders are mediated by another disorder. In the following slide, a preschooler with an anxiety disorder, but not ODD, is no more likely than a child without a disorder to have CD. Notice how ODD seems to be a central mediator between the relationships of other disorders to each other. [SLIDE ] It almost appears that ODD is a gateway to other disorders. Of course oppositional behavior is normal to some degree in two and three-year-olders. But the question is whether any individual child is more oppositional than expected for age and gender. Here, the use of extensive age and gender specific norms becomes crucial. By using a cutoff, say the 90th percentile, we can have some confidence that an intervention is warranted. In this case, parent training has been shown to be an effective intervention for young ODD clients. IMPAIRMENT A finding that a preschooler has more symptoms than expected for age and gender is not enough to demonstrate the need for intervention. It is important that your assessment also shows that the symptoms lead to impairment (in social, educational, or developmental status such as play). Percent Impairment of Preschoolers with Diagnoses [SLIDE ] Data from the preschool studies show a strong relationship between a diagnosis and the number of symptoms and impairment. However, even for many children who do not meet the threshold for diagnosis (“sub-syndromal” patterns), there may be significant impairment. This supports the notion of a continuum of impairment as a function of the number of symptoms. When you examine a child and they have many symptoms, but not enough to make a diagnosis, you still have to consider whether there is some impairment present. ARE THERE HARMFUL EFFECTS OF PSYCHIATRIC LABELS ON PRESCHOOLERS? If you type that question into Google you will get literally thousands of “articles” berating the use of psychiatric labels in children. After reading a few dozen of these articles you may become impatient for any evidence or data to support the conclusions. Many of the articles come from Scientologists or people who can quote Tom Cruise, but cannot quote a single empirical fact to support their argument. A few will quote Peter Breggin or other well-known advocates against psychiatry, particularly those against the use of medications. Most however, are simple expressions of outrage based on no data whatsoever or an anecdote from personal experience. Anecdotes are not data. I adhere to the philosopher David Hume’s method of evaluation: “if it has no tables or data, commit it to the flames.” But we mustn’t stop there; the next step is to use the vast resources of electronic searches in Ovid’s Medline, or other large databases. There it is equally frustrating to find that there are literally hundreds of thousands of articles on children, mental health, stereotyping, self-esteem, side-effects, diagnosis, and various combinations thereof; but not a single study that appears to demonstrate the harmful effect of psychiatric stereotyping or labeling on children. Am I missing something? Or have there been some acceptable empirical studies of this common attribution that simply have not been captured in my database searches? I confess that in my own experience, weighing the benefits of good assessment and treatment against the fear of labeling effects leaves little doubt that the benefits outweigh the risks. After all, finding a correct label means there is some guide to action. There is benefit to knowing what the onset, course, and response to treatment is likely to be for a known disorder. A diagnosis is not a harmful label; it is an injunction to informed action, unless 2000 years of medical wisdom is to be ignored in the face of fear and ignorance. ADVERSE FAMILY CIRCUMSTANCES, PARENTING AND PSYCHOPATHOLOGY IN PRESCHOOLERS Finally, let us consider the question of whether classifying or diagnosing a preschooler erroneously places an emphasis on innate, biological or genetic problems rather than environmental problems. Does this turn us away from thinking about the relationships between parents and children, or from the dangers inherent in the wider environment? Isn’t it true that much of the advance in our understanding of childhood mental illness comes from a long tradition of uncovering the kind of trauma, abuse, and neglect in the family environment, or the well-documented effects of poverty, poor housing, isolation, and what Emile Zola called, “The short and simple life of the poor?” The answer of course, is that there is a false dichotomy here. We now know that the unfolding of the somatic development of the body and brain, the role of the genes, is markedly subject to the environment in which genetic expression must take place. The simple fact of the matter is this: if you hold environmental variables constant, then emotion, behavior and mental development are governed by the genes. But if you hold the genetic variables constant, any variation of the phenotype is due to the environment. All diseases and disorders appear to fluctuate as a function of both environmental and genetic variation. Let us abandon this false dichotomy between genes and environment, nature and nurture, and recognize that a valid clinical assessment requires a careful investigation of both sorts of influence on a particular child. We believe that the innate genetic expression of many of the kinds of mental illness will be found in the very young child, even those blessed with an optimal environment. On the other hand, many children with normal genetic endowments may suffer from the slings and arrows of a dangerous world in which they live. Remarkably, the little available data on the role of family relationships and parenting in preschoolers appears to show that early adverse family circumstances and parenting characteristics do not contribute to the prediction of later psychopathology once child characteristics are accounted for. In a longitudinal study of 420 two-to-three years olds followed up at 10 to 11 years, of the environmental risk factors, only stressful life events contributed independently to the prediction of later externalizing behavior problems [6]. CONCLUSIONS In summary, I argue that even though there is rapid and variable developmental changes, most of the broad patterns of illness found in older children and adults will be present in a certain percentage of preschoolers. Extremes of temperament patterns do predict later mental illness, but temperament alone is not sufficient to explain the many types of individual disorders that will appear in preschoolers. With all of its faults, DSM nevertheless is a helpful guide to the variety of disorders to be found in very young children. Appropriate modifications of the DSM for developmental stage in preschoolers have good supporting data from the available epidemiologic trials, and from our own normative studies. We believe that the benefits of early classification leads to appropriate intervention strategies, and that whatever the downside might be in terms of stereotyping or labeling, the benefits are indisputable. In all of these arguments, the presence of assessment tools for disorders and development in the preschool age relies upon careful census-based age and gender-based norms. It is only from a good foundation of normal behavior and development that we can venture into the world of the preschool child. REFERENCES 1. Egger, Helen Link & Angold, Adrian (2006). Common emotional and behavioral disorders in preschool children: presentation, nosology, and epidemiology. J Child Psychology & Psychiatry, 47(3), 313-337. 2. Cole, Pamela M; Zahn-Waxler, Carolyn; Fox, Nathan A; Usher, Barbara A; Welsh, Jean D. (1996). Individual differences in emotion regulation and behavior problems in preschool children. J of Abnormal Psychology, 105(4),518-529. 3. Egger, Helen Link, Erkanli, A., Keeler, Gordon, Potts, Edward;Walter, Barbara K. & Angold, Adrian (2006). Test-retest reliability of the preschool age psychiatric assessment (PAPA). J of the American Academy of Child & Adolescent Psychiatry, 45, 538-549. 4. Wilens, T.E., Biederman, J., Brown, Sarah, Tanguay, Sarah, Monuteaux, M.C., Blake, Christie, B.S., & Spencer, T.J. (2002. Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD. J American Academy of Child & Adolescent Psychiatry. 41, 262-268. 5. Lavigne, J.V., Binns, Helen J., Christoffel, Katherine K., Rosenbaum, Diane, Arend, R., Smith, Karen, Hayford, Jennifer R., McGuire, P.A. (1993). Behavioral and emotional problems among preschool children in pediatric primary care: prevalence and pediatricians’ recognition. Pediatrics, 91, 649-655. 6. Mesman, Judi; Koot, Hans M. (2001). Early preschool predictors of preadolescent internalizing and externalizing DSM-IV diagnoses. J of the American Academy of Child & Adolescent Psychiatry. 40, 1029-1036.

New Drug Trials for ADHD: Who is Watching?

2009-05-26T09:50:00.004-04:00

Stimulant drugs like methylphenidate and dextro-amphetamine for ADHD are among the most well-established therapeutic drugs in all of psychiatry (see for example my article, 40 years of methylphenidate treatment of ADHD, J of Attention Disorders, 2002, Vol. 6, Supplement 1). One reason for this general acceptance is a large number of well-controlled trials repeated by many different investigators over the years. But more importantly, frequent clinical use over many years supports the conclusion of the efficacy and safety of these drugs. Though not without some controversy and certain drawbacks, on the whole it is safe to say that most reputable scientists and clinicians find these stimulants to be of substantial value in treatment of an otherwise very refractory disorder. But as the success of these drugs has encouraged pharmaceutical companies to seek even more effective drugs, or to market drugs that provide an alternative for those patients who prove refractory to the stimulants, many novel chemical agents are appearing in new drug trials. In addition, potent new anti-psychotic drugs are being touted as safe and effective. Are the drug trials for these newer drugs adequate, or are there serious loopholes in the methodology that allow ineffective or dangerous drugs to be approved? Here's what often happens in the development of a new psychoactive drug for ADHD. Someone has an idea that a particular molecule, perhaps from a failed trial of some other condition like depression or Alzheimer's or schizophrenia might work with ADHD. An "open label" trial by a proponent is found to produce some favorable response in a few patients by a welll-known clinician treating ADHD, suggesting to the pharmaceutical company that it is worth doing a more carefully controlled trial. (Of course it is financially profitable for the clinician to find positive results because further trials will potentially bring in big bucks, and the pharma company tends to trust the clinical judgments of well-known clinician experts in the field.) Sometimes a well-meaning investigator finds that although the main experiment failed to confirm the efficacy of the drug, a few patients showed a dramatic improvement, warranting a further look. One of my favorite maxims is that "looking for a subgroup in an experiment is a sure sign of a failed experiment." Pursuing a small lead in a failed experiment is like betting on a nag that put up a good effort but lost. But pharmaceutical companies have experts in drug trial methodology who also know that they must conform to the standards set by the FDA, and eventually must fund large trials that employ a standard double-blind design, using approved measures. Typically, this means that patients are randomly assigned to a treatment group and a placebo control group, and assessed with a symptom list of some sort representing the current diagnostic standards, such as a DSM-4 checklist. After getting measures before treatment starts ("baseline") subsequent checklists or scales are filled out based upon an interview with the patients (or in the case of children, their parents and/or teachers). So a parent might respond to questions about hyperactivity, inattention, defiance, or social behavior for example; and the investigator will then fill out his or her own scale, or perhaps a "global" judgment of overall improvement or change. Sounds reasonable. But wait, there are some issues here! What if the parent or teacher or the patient is able to "peek through the double blind," that is to guess which treatment they are receiving? Not that they would consciously cheat, but because it is well-known that the first thing a patient or parent wants to do is please the doctor, or to do what they think the investigator or doctor wants to find. This is called the "demand character" of an experiment, which every experimenter learns to expect and tries to avoid. But how can the patient or parent peek through and know which treatment is being used? Easy. Every drug produces some subjective effect, perhaps a side effect like stomach pain or nausea, or a racing heart, or a thousand other subtle or obvious bodily changes. When the patient experiences one of these effects, they will often respond in the way their brain expects. This is called the "cognitive potentiation of a bodily feeling." Let me illustrate from a very early experiment carried out by Stanley Schacter. Subjects in a drug experiment were told they would receive a drug that would cause some changes in their mood. One group was told that the drug (epinephrine) would make them feel euphoric, and another group was told that the drug would cause them to feel depressed. Now epinephrine is a stimulant that typically will increase heart rate, but the behavioral effect that occurred in this experiment depended upon which expectation the subjects had about the drug, and they acted accordingly. Even though epinephrine produces a number of peripheral signs of stimulation, patients interpreted those signs as if they got a depressant, not a stimulant. Another favorite experiment was with medical students who were asked to drink coffee and then have measures of heart rate, respiration, and skin temperature taken. One group saw the experimenter brew the coffee from a brand coffee jar (Folger's as I recall), and the other group saw that the jar was labeled as decaf. In fact, both groups got only decaf. But the supposedly "loaded" coffee group had increases in heart rate, respiration and finger temperature, while the "decaf" group showed no changes. This study illustrates how the subjects' expectations can manipulate their own bodily responses. Returning to ADHD, we now see that when an investigator uses the report by a patient, a parent, or a teacher, there is the possibility that "improvement" will simply be the desire to please the investigator as informed by their own knowledge of the "active" treatment condition. Thus, the double-blind is leaking all over the place. But there is an even more deadly threat to the integrity of these experiments. In many cases it is the most senior member of the investigating team, the accredited specialist or doctor, who records the signs of improvement. This is so because there is always the possibility of significant "adverse events" or AEs caused by the drug, and the senior investigator must be vigilant in detecting and reporting these AEs for the safety of the patient as well as for eventual calculation of the risk and benefit of the drug. So in these trials, the dose of the drug will usually be adjusted to get a good response without undue side effects or AEs. But if the doc is knowledgeable about the side effects, isn't he or she also then apprised of which drug the patient is receiving? Obviously. Well then, even the honest doc might unconsciously want to please their sponsor by finding positive results. And of course if it is an openly greedy doc, what would you expect? Funny, though, when I raise these objections in pharmaceutical meetings about the drug results, nobody seems to care. The drug companies persist in believing that the investigator is objectively recording their observations as far as improvement is concerned, while nevertheless being apprised of the side effects. And the investigators themselves never question their own objectivity despite the clear knowledge of who is being treated with what. These problems might not matter much with the proven stimulants because the efficacy is often so dramatic; but when a more subtle drug effect occurs, who knows what might happen? In fact, I know of more than one such drug that got approved but began to falter after a longer period of clinical use showed the true lack of efficacy. The old maxim in psychopharmacology is worth remembering: "Use a new drug quickly, while it still works." This is not to allege conscious impropriety. Investigators may truly believe they are objective and drug companies are simply following the models set up as appropriate by the FDA. But there are some simple solutions to these dilemmas, but not without cost. One solution is to use an "active placebo," where a dummy drug is used as a control, producing some bodily effects without much behavioral effect. But this solution has its own problems and is seldom used. Another solution, and the most logical one, is to have one well-trained physician recording and judging the side effects (and therefore changing the dosages during the adjustment phases of the experiment), and a different experimenter/physician recording the improvement. This requires careful scripting of the protocol for inquiring about improvement, and careful shielding of one investigator from the other colleague. I often wonder how much subterranean motives influence the investigator, who stands to profit from a successful trial, and the drug company which seeks FDA approval and a rich reward for their investiment. In general I choose to believe in the honesty and integrity of both the docs and the companies. But I also believe in the deeper effects of "demand qualities of the experiment," and the power of placebo when potentiated by cognitions, therefore that we must employ the most rigorous protections possible in our experiments on behalf of our trusting and troubled patients.

Neurofeedback and ADHD: Save your money!

2008-11-24T10:35:00.003-05:00

At one point many of us in ADHD World were very interested in electrical activity in the brain. There were dramatic demonstrations around, such as using electrical output of the brain to control a toy train set. There seemed to be a nice set of brain rhythms in separate categories, going from very slow during sleep phases, to very fast during active thinking and cognition. Measurement was easy. There seemed to be correlations with mental state, as when the large-amplitude waves between 8 and 12 Hz were accompanied by a state of alert relaxation. I became entranced with the idea that one could use those rhythms to alter mental states. I was convinced that all the benefits of meditation could be created by finding the key electrical signatures for meditation, and using those outputs (easily obtained with simple amplifiers and filters), to achieve the Nirvana-like states attributed to meditation. In my naive and excited optimism I carried a portable EEG machine to Nepal to measure the brain activity of highly practiced monks during meditation, (After all, attaching electrodes to the scalp of bald monks beats the messy efforts with long-haired practitioners at home.) The kindly head of the Buddhist order in Nepal, the Bikku Sumangala, made arrangements for me to obtain my data. He laughed at the idea that I would "find" attention through those little wires attached to the head. Instead he said he could show me how to do it very easily without the wires. So he gave me instruction in meditation of the "mindfulness" variety, and I abandoned my silly escapade in favor of studying the readily observable processes in my own mind. As he said, "Simple, but not easy!) However, when I returned to my laboratory, then at the University of Pittsburgh, I continued to use biofeedback with a variety of patients, particularly those with anxiety and various kinds of muscle pain and headache. I gradually learned that the biofeedback instruments could mostly be replaced by simple relaxation instructions and practice. I had one instructive patient, a middle-aged woman who suffered from recurrent tension headaches, whom I treated with simple relaxation patter, with great success in the lab, where I could see in the sessions how well her frontalis muscles relaxed when I gave her the verbal relaxing patter. I gave her a tape with my voice giving the relaxation instructions, to play as homework. After a couple of weeks she returned saying that this cognitive approach was working very well; headaches were gone! I commended her for doing her homework and listening to the tape, whereupon she said, "Oh I found I didn't have to actually listen to it; I just carry the tape around in my purse and it works just as well as listening." Well, we might call this "cue-induced relaxation" in which a visible object has become a cue for the verbal material previously learned. But even this bit of technology can be supplanted rather easily. But the fact that the EEG machine could readily differentiate the different levels of electrical activity available at the scalp, and that the different rhythms could be used to trigger events that could reward or increase some rhythms and decrease others, as for example, increasing alpha or beta rhythms while decreasing Theta or Delta rhythms, led many others to the idea that it might be possible to permanently change the resting states of the brain, or to give the practitioner a tool for correcting undesired mental states (like the sluggish or sleepy brain which is often associated with conduct problems). Thus was born a rapidly expanding movement called Neurofeedback, where practitioners charge substantial fees over many sessions to alter the brain states and to give some self-control over those brain states to the clients. In ADHD and conduct disorders, it was in fact well-known that they tended to have more slowing of occipital waves on average, and less of the faster rhythms associated with higher order mentation. By sounding a simple tone or giving some visual feedback when the desired rhythms occur, it turns out to be quite true that for most people they will be able to alter their own brain rhythms! But now comes the crucial question: How well does that self-alteration of brain wave control translate into improved behavior? Do the symptoms of ADHD or conduct disturbances, --or anxiety or whatever--stay improved over time? How does one find out? The obvious answer is, you ask the client. But here is a problem, doesn't the mere expensive exercise itself create a large placebo effect? Well, yes. The fancier the machine, the more convincing the therapist, the more that plain old placebo effect takes over. Okay then, it seems obvious that practitioners can simply do some controlled studies in which one group gets real feedback, one group gets false feedback, and perhaps one group gets no feedback. Sounds easy, but in practice there are significant problems. How does one give false feedback that seems real and does not discourage the client because nothing is happening? Remember that the client begins to shape their EEG when the feedback tells them what to increase or disregard. False feedback would be discouraging since no changes in brain output would be there to reward changing in the right direction. Another problem is that clients might well be on some medications to improve their behavior. Many of the so-called supported trials reported in the literature ignore the fact that many of the biofeedback patients were also getting treated with a stimulant drug or other drug. If so, this could likely confound the results or wash out any changes due to the feedback. Sure, one could pick unmedicated patients, though this creates a problem in how representative the ADHD sample would be. Having clients evaluate their treatment has a serious flaw as well. The client is not "blind" to the treatment conditions, and typically wants to follow the doctor's expectations and improve according to the prescribed outcome. This is called the "demand characteristics" of the experiment, and is often the main thing causing the treatment to "work." So to counter this problem one can have independent evaluators: not the doctor giving the treatment and aware of the side effects, but truly independent observers, perhaps teachers or parents, who can evaluate the behavioral changes without knowing which treatment was being given. Surprisingly, there are no controlled evaluations of Neurofeedback that deal with the various threats to experimental validity. The main clue here is that most Neurofeedback specialists are "true believers" who don't need evidence to bolster their belief in the programs. They charge a lot of money and show little interest in the scientific support for treatment effects for tracking the followup status of their clients. The key is that the practitioners do not publish controlled outcome studies in reputable peer-reviewed scientific journals. Until they do, clients are advised to ignore the blandishments of the seductive machines and pretty blinking lights. But they may want to look into mindfulness meditation as a potential avenue for the simple, but not easy approach. In future posts we will look at the evidence for the value of mindfulness meditation or other attention-training approaches.

Executive Function and ADHD

2008-11-17T10:29:00.002-05:00

"Executive Functions" are brain processes that control other brain processes. Specific tasks that involve sensory functions, movement, perception, preparation for action, etc. are organized, regulated, and controlled by higher-order circuits in the brain. We liken executive functions to those of an executive or CEO in a big corporation, or to the general at the rear of the battlefield or the conductor of a symphony. He or she does not personally sell, do the accounting, collect receipts, schedule the airline flights, do the advertising for the company, or go out on patrol or dig the trenches. (Perhaps the occasional conductor such as Leonard Bernstein will play the piano while also conducting; some CEO's or conductors are genius enough to multi-task at times.) But the CEO makes the major decisions and policy programs for the company, does the strategic planning, and selects the managers who design and carry out specific tactics. The CEO initiates programs, plans the strategies, monitors the progress, and evaluates the outcomes. The CEO adapts and changes the program as new circumstances require. But the CEO is vulnerable. If the secretary is absent for a day, scheduling is hampered, monitoring is suspended, and there may be a temporary loss of control. The CEO is effectively brain-dead as far as the momentary functions of the corporation are concerned. Of course, a good hierarchy always includes trustworthy backups, 3-star generals, or first violins who can take over in an emergency. So too in the brain; not all executive functions are vested in a single overall Director, and it is the redundancy of the developed brain that carries on under temporary emergency conditions. For example, fMRI brain imaging shows that when one of the major executive functions carried out in the anterior cingulate (an area of the brain involved in regulating attention) is impaired in an ADHD adult, the functions are apparently transferred to lateral areas of the brain not typically designed for those functions, perhaps with some loss of proficiency but enough to allow continued overall processing to continue. So executive functions are powerful functions, mainly located in the newer areas of the brain (the frontal lobes, both orbital and lateral areas) that include such processes as working memory, inhibition of motor response, and selective attention). Many observers of ADHD have proposed that these Executive Functions are the primary processes that define ADHD. They argue that the ability to plan, organize, initiate and complete tasks, monitor the results of actions, inhibit impulse, regulate time requirements such as being on time or estimating the time to do things, and a host of other functions are the hallmark of ADHD; in fact constitute the primary deficits of ADHD. But does evidence really support this appealing idea? There are several reasons why I think not.

First of all. there is the problem that the very definition of what constitutes executive functions varies from one authority to another; there is no standard or accepted definition.
When parents or teachers fill out checklists or ratings of executive functions, there appears to be agreement with standard definitions of ADHD (e.g. with DSM-IV clinical symptom definitions), but there is no relationship to executive functions as measured by actual cognitive functions measured in performance tests. (For instance, tests of working memory do not agree with ratings of memory performance.
Impairment of executive functions is common in many disorders other than ADHD, for example anxiety, depression, psychosis, etc. In fact, executive dysfunction cuts across almost all mental disorders and cognitive impairments. It would thus appear to be more a consequence of disorders than a specific cause of disorders.
Finally, a number of investigations fail to find the executive dysfunctions postulated for ADHD.

For these reasons I believe that while it is useful to assess executive functions in ADHD, particularly since these functions may be trainable and coachable, a full assessment of ADHD requires a much broader range of symptoms and diagnostic criteria.

The myths of ADHD

2008-10-14T09:41:00.000-04:00

Over the years I have encountered many skeptics who believe neither in medicating children nor in labeling and diagnosing them. Deep, instinctual protective feelings towards children become displayed as unwavering hostility to all who prescribe psychiatric medications or attach a label to children. Anti-labeling and anti-medication becomes a lifestyle, a religious quest, an angry flag-bearing march against psychiatrists, psychologists, pharmaceutical companies, and even government-sponsored research. Books and diatribes about Ritalin nation, running on Ritalin, normal temperament, suppression of creativity, drug company conspiracies, myth of the hyperactive child, drugging into submission, medicalization of normal behavior, etc.—have all been part of the history of pediatrics and child psychiatry. More recently the attacks have broadened to include adult ADHD as well. Unfortunately there is always a grain of truth in these arguments. There is indeed over-prescribing, some children whose behavior is merely at the extreme end of the normal curve of temperament, some children whose life situations make them hyperactive and whose environments are the real problem; some who become zombies in the classroom from over-dosing, and some pharmaceutical companies who use lax criteria and exaggerate the numbers and the successes in treating with their drugs. As I suggested earlier, there is indeed some over-treatment, over-diagnosis, sloppy research, big pharma skullduggery in collaboration with corrupt researchers—matters well-covered in the media and in blogs by reputable critics (see especially the blogs on the subject by Barney Carroll). But the real world is complicated. Science may take a while to catch up with flawed opinions floating about in peoples' heads as if they were fact. We now know that there is also a degree of reality behind the diagnoses, brilliant successes with some of the treatments, justification for early interventions; that there are multiple genetic and environmental risk factors associated with many childhood psychiatric conditions. Though not ready for clinical use as yet, and notwithstanding the excesses by fraudulent practitioners of neurofeedback or brain scanning, there are nevertheless sound neuroscience advances at all levels that attest to the reality of conditions like ADHD; true diseases whose definitions are based in the genetics, biochemistry, brain morphology, and physiology of modern science. I also believe that there are many honest collaborations between pharmaceutical companies and rigorous scientists that have made tremendous progress possible in therapeutics and basic knowledge about psychiatric illness in children. That transparency and close oversight are needed in those collaborations seems obvious as well. I am prompted to bring these issues up because I recently read what I think is the most convincing and brilliant conversion by a standard critic into a more thoughtful advocate for appropriate diagnosis and treatment: the blog by Judith Warner, which I highly recommend: http://warner.blogs.nytimes.com/2007/03/01/second-thoughts/ There are many brilliant and thoughtful observers out there who have been self-assured critics of ADHD, thinking it all a set of myths, until they have such a child themselves, or run face to face with these children in the lives of family or friends. The more brilliant the opposition, the more stunning the conversion to the reality.

How many ADHD children and adults are out there?

2008-10-08T10:47:00.000-04:00

My mentor, Leon Eisenberg, once commented that when we started out in the 1960's studying "hyperactive children" --now called ADHD--it was hard to convince anyone that they really existed or that it mattered. Especially doubtful were the British, led by their great scholar Michael Rutter. Now the schools and homes seem to be flooded by them, to the point of an epidemic. Although my old colleague Paul Wender, also at Hopkins in the 1960's, had first alleged that adults also had ADHD, nobody took that idea seriously until recently. Now there is a claim that their prevalence even exceeds the 2 to 3 percent of child ADHD, and over the last 5 years their prevalence has steadily and rapidly increased. Recently the National Comorbidity Survey of the World Health Organization (WHO) under a brilliant Harvard scholar, Ron Kessler, has placed the figure at 4 to 5 percent whereas the estimates for childhood ADHD average around 2 to 4 percent. What gives? Can there be more adult ADHD than child ADHD? First, there are now dozens of studies throughout the world that consistently place childhood ADHD as high as 10 percent of the population, and averaging round 4 to 6 percent. Are there really 10 kids out of a hundred with ADHD (3 or 4 in every average classroom)? Well how does one KNOW? Remember that these studies usually involve hundreds or thousands of children, so that defining a case cannot usually involve individual clinical interviews. Instead, they may involve telephone surveys, checklists of symptoms, or surveys of parents. Remember too, that according to the standard psychiatric definition (the Diagnostic and Statistical Manual of the American Psychiatric Association, now in its 4th revision, called DSM-4), there are 5 criteria that must be met. The most important of those criteria is the one that requires that the symptoms not be better explained by some other illness; that is, a "differential diagnosis" must be made. If it's autism, or depression, or anxiety, etc., then the 18 ADHD symptoms could be caused by one of these other illnesses. But wait! Doesn't that mean you have to do a COMPLETE psychiatric examination? If you don't then the presumed "case" of ADHD could be something else, and the total count of ADHD cases would include all the other possible diagnostic contenders. Now examining all of the epidemiological studies of ADHD, the only one that I know of that actually used a complete diagnostic interview on enough children to form a reliable prevalence estimate was a study by Adrian Angold and Jane Costello in the Western counties of North Carolina. Their prevalence rate for ADHD: less than 2 percent. Incidentally, they found that a great many children who did NOT meet ADHD criteria were being treated for it, and a great many who DID meet criteria were not being treated for it. Obviously a correct diagnosis is necessary to avoid both kinds of mistakes. Wow! ADHD IS BOTH UNDERESTIMATED AND OVERESTIMATED at the same time, and they are being unter-treated and over-treated at the same time. Now what about the adults? The big problem here is that there are no agreed-upon criteria for adult ADHD, though there is much work being done to alter the criteria to account for developmental changes in symptomatology, age of onset, and types of impairment associated with the condition. DSM-V will undoubtedly give us the basis for a real epidemiologic survey. However, the afore-mentioned WHO study started with a subsample of the very large survey carried out around the world, and by using statistical methods (e.g. imputing the actual numbers for the whole sample from a smaller subsample), they used 6 symptoms that were included in the original survey, to arrive at a prevalence estimate for adult ADHD, based on followup telephone interviews of the smaller subsample. The result: 4 to 6 percent prevalence of adult ADHD. Here again, there really is no full psychiatric interview, so that in my mind these high figures must remain suspect. Incidentally, I am not reassured by the fact that this "WHO Study", which I participated in, was sponsored in part by a drug company, and that shortly after the first findings the drug company was using the 6 symptoms as a diagnostic guide for recommending adults to see their physician for possible treatment. So here we have another possible explanation of the explosive growth of adult ADHD: it is a boon for pharmaceutical companies who are now virtually all scrambling to get FDA approval for ADHD drugs in children to be approved for adults as well. Don't get me wrong; adult ADHD is a real problem, and one that can be successfully treated by medication and other methods, and is a condition that has serious consequences for the patient and their families. But if ADHD, as we and most scientists agree, is a developmental problem starting early in life, then it seems unlikely that the true prevalence for adults can be more than the prevalence for children. Adults will pass through the age of risk for many other psychiatric and emotional conditions than for children, so that they will have more comorbidities and more impact on their adult lives than they did as children. On the whole they could be sicker, though many compensate or adjust to their illness, especially those well-treated as children. But it is precisely these other conditions which might better explain their illness and dysfunctions, so they may be mis-diagnosed as ADHD when they are not ADHD cases at all, just as many children have likewise been mis-diagnosed because their symtoms could be due to other disorders that were not screened for. The bottom line: symptoms alone do not define ADHD. It is a mistake to make the diagnosis without carefully ruling out other explanations. To do this requires a sound clinical interview by a trained mental health professional.

Science or Scam: Neuro-imaging for ADHD?

2008-09-24T15:04:00.000-04:00

More than a dozen years or so ago I was attending a conference in Israel on ADHD when one of the organizers--a neurologist-- asked me to please address the problem of Dr. Daniel Amen's claims about his subtyping of ADHD through the use of the SPECT imaging technology. The problem she said, was that many of her patients were flying from Israel to the U.S. in order to be "subtyped" and then treated by Dr. Amen in California. Single photon emission computed tomography (SPECT)) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient. One disadvantage of this technology, in contrast to MRI or fMRI, is that it requires giving a dose of a radioactive tracer. In response to Dr. Amen's talk I asked to see any data supporting his claims. He responded by saying that he had over 12,000 cases on which to base his typology. "What statistical methods did you use?" I asked. He replied that they had not been published yet, but that researchers like me would have to undertake such a huge job. More recently, 11 years later in La Jolla, California I happened to be on a panel with Dr. Amen and the same issue was raised about publications. He responded that there was now a publication, but he didn't recall the name of the journal; but he asked one of his colleagues in the audience for the name. The colleague looked puzzled, threw up his arms quizzically, and said he didn't know. So much for supportive scientific proof. A prominent neurologist and imaging researcher, George Busch, M.D. happened to be on the same panel. He unequivocally denounced Dr. Amen's claims and asserted that no respectable scientist had yet to find a way to use neuro-imaging to make those clinical subtype distinctions, let alone a diagnosis. Work by Jay Giedde, Judy Rapaport, and Javier Castellanos at NIMH with MRI and fMRI have indeed shown that there are important brain differences between ADHD and normal controls, both cross-sectionally and developmentally. But no one claims that any diagnostic rules from those data are capable of the precision required to beat clinical assessments. Here's what Dr. Amen claims about ADHD subtypes: Type 1 — Classic ADHD. Symptoms such as short attention span, distractibility, disorganization, procrastination, poor internal supervision plus hyperactivity and impulsivity.* Type 2 — Inattentive ADHD. Classic ADHD symptoms, but instead of hyperactivity, there is low energy.* Type 3 — Overfocused ADHD. Classic ADHD symptoms as well as negative thoughts and behaviors, such as opposition and arguing.* Type 4 — Temporal Lobe ADHD. Classic ADHD symptoms plus irritability, aggressiveness, and memory and learning problems.* Type 5 — Limbic ADHD. Combines ADHD with depression and low energy and decreased motivation.* Type 6 — The Ring of Fire. Cross between ADHD and bipolar disorder. Characterized by moodiness, aggressiveness, and anger. Now any experienced clinician will undoubtedly agree that these are recognizable forms of presentation at a child clinic. In fact, these are classic descriptions from the literature: the hyperactive/impulsive type; the inattentive type; the overfocused type (e.g. Kinsbourne's type); the hypoactive type, etc. But are these "types" confirmed by an appropriate methodology as variants of ADHD? Where is the cluster analysis or factor analysis of large samples characterized through rigorous clinical documentation? Where are the structured or unstructured interviews and histories to validate the diagnosis? What are the statistical boundaries among these so-called types? What is the evidence that they respond differently to treatments or have other biological or genetic markers to distinguish them? If I had 12,000 cases in my database, I would not waste a day before exploring the typologies that might be hidden there. Amen's work is classic quasi-scientific mystification: the failure to distinguish between anecdotes and data, and between hypothesis and fact. Like all fringe quasi-scientific appeals to a needy public, there are classic signs of when the patients are being fooled: 1) There is an impressive and truly science-based technology, so sophisticated that the ordinary public must take the claims on faith; 2) The proponent of this new method, though possibly trained in traditional clinical and scientific paths, breaks with the majority of scientists and fails to pass the test of peer review; 3) The proponent himself (or herself) is too busy seeing patients and collecting large fees to do the necessary research themselves; 4) The proponent tirelessly appears at conferences and seminars worldwide, and develops an adoring but uninformed following despite repeated criticisms to produce real data; 5) Standard treatments are often the outcome from the elaborate workups and tests, though actual followup studies are seldom provided. I have to admit that personally Dr. Amen is charming, well-informed, and well-trained. He gives a convincing talk, and if I were an uninformed normal patient, I would probably agree that there is no definitive biological test for ADHD, no pathogonomic sign, and a truly complex clinical picture. I might possibly end up in desperation spending thousands of dollars after seeing the lovely colored pictures of the brain, with hot spots where ADHD resides. But fortunately, I have been around long enough to spot mumbo-jumbo when I see it. Let the buyer beware.

Fish Oil as a treatment for ADHD?

2008-09-16T11:53:00.000-04:00

Some physicians are now recommending fish oil in the form of omega-3 fatty acids or PUFAs (Poly-unsaturated fatty acids) as a therapy for ADHD children, adolescents and adults. This is partly in response to the persisting fears of parents about stimulant medications and partly on the basis of the always-hopeful findings in the literature, i.e. on the basis of inconclusive studies that "suggest further research is needed." As in most alternative therapies, some elements of basic neuroscience are cited as the rationale for the therapy, followed by "preliminary studies" which give hopeful signs (one might cynically say especially signs of future funding from government or pharmaceutical companies). In this case there are a number of animal studies which compare spontaneously hyperactive rats with their cool Sprague-Dawley cousins, who show signs of better cognition after dietary supplementation with PUFAs. Also, it appears that lack of these fatty acids are known to impede neural development in young babies. However, as for the scientific rationale, one respectable scientist says that, "...our current understanding of the importance of essential fatty acids (EFAs) and their metabolites to optimal brain function is based on an enormously complex set of interlinked biochemical, neurological, and laboratory observations. The applicability of these research findings to children with attention-deficit/hyperactivity disorder (ADHD) is unknown." (Betsy Busch, Polyunsaturated fatty acid supplementation for ADHD? Fishy, fascinating, and far from clear. J. Devel. & Behav. Pediatrics, Vol 28(2) Apr 2007, 139-144). What about clinical trials? One comprehensive recent review (E.H. Clayton, et al., Acta Neuropsychiatrica, Vol 19(2) Apr 2007, 92-103) found that 4 randomized controlled trials showed uncertain benefit for ADHD and no benefit for autism and bipolar disorder. A typical research story is illustrated from a controlled trial by A. Richardson and colleagues, who studied 41 children with ADHD and LD randomly assigned to highly unsaturated fatty acids (HUFAs) or placebo for 12 weeks. They found a mean improvement on 7 of 14 parent rating scales, "reaching significance levels on 3 of 14 scales." (Progress in Neuro-Psychopharm. & Biol. Psychiat. Vol 26, 2002, 233-39) Of course, they did not adjust for multiple tests, so technically the results are nil, but they call for further research.. By 2006, when reviewing the field, the same author concludes, "Omega-3 is not supported by current evidence as a primary treatment for ADHD or related conditions...." but still calls for further research. (A.J. Richardson, Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int. Rev. Psychiat. Vol 18, April 2006, 155-172). Well, this is merely the research game as we have come to know it. I too have been enticed by small pilot studies that lead to larger grants (as in my flirtation with the Feingold diet studies, though there I took satisfaction in stopping a national trend sweeping the country which was diverting many parents from worthwhile treatments). One final research note on the dietary studies that also applies to drug trials involving parents and children. Many of these trials use apparently blind judgments by the physician which are in turn based upon reports by parents. But virtually all drugs create subjective awarenness by the patient that something is happening, and patients follow the demand characteristics of the experiment to give some response they think is expected, and parents as well as physicians become aware of side effects which allows a peek through the double blind. Note that in the previous study above the effects were found in parents but not by teachers (who are generally much more unaware of side effects and subjective bodily changes). When a trial shows parent reported changes but not teacher reported changes, one needs to be very suspicious about the signficance of any positive findings. All of those physicians out there who use the DSM-IV rating scale or global judgments as their outcome measures are likely to be subject to a positive bias about the drug being studied. After all, they get paid by the pharmaceutical companies and there is strong incentive to produce positive results and continued study. I have made this point many times at advisory committee meetings, but I have yet to find a single pharmaceutical company that pays attention to the suggestion of using blind raters who are separate from the physicians controlling the monitoring for side effects or adverse reactions. My conclusion from reviewing the literature on Fish Oil as therapy for ADHD is that it clearly is not proven. There are two therapies supported by research over a 40 year period: the combination of behavioral management (both in the classroom and at home); and stimulant drugs. But I make the following observation from my practice: it is usually quite useless to argue with a parent when they are predisposed against the use of drugs, no matter how noxious the child's behavior has become in their own lives. For those parents I make a therapeutic alliance by saying, sure, there are dietary therapies. First, make sure your child has a well-balanced diet, especially limiting their preference for high carb foods, and making sure there is plenty of protein at breakfast (I give them a pretty good story from our studies on this subject). I take a dietary history and recommend a 3-day diet diary, recording everything the child eats, and use it to steer the child and family away from obvious imbalances (there is good evidence that ad liibidem access to carbohydrates leads to an over use of them, especially in ADHD and Conduct-Disordered kids). I recommend limited access to sugar and sweets, but always balancing them with protein. For adolescents I am especially cautious about caffienated drinks. Eventually most parents return to the clinic after a few weeks saying, "Yes he (or she) is much better! But, you know, it's still a problem. What else can I do? I still don't want Ritalin." "Ahem, Madam, I agree and I can recommend a great medicine that is not Ritalin! (Well, it might be Metadate or Focalin or Adderall or Concerta or one of the other possibilities down the line when those don't work. But see my physician colleague, he (or she) knows all about it and can give you the latest medicine that works...") You get my drift. Since I do not myself prescribe, I rely on my savvy physician colleagues to know about the MTA study and the nuances of psychopharmacology that make for an effective treatment plan over the entire lifespan. (More on the MTA study in future postings.)

Food and Behavior

2008-09-15T10:36:00.000-04:00

A colleague of mine who works in the public school system recently remarked that one of the parents with an ADHD child wanted to know whether her physician was correct in prescribing fish oil instead of a stimulant medication for her pre-adolescent son. This immediately prompted a deja vu flashback to my years studying the role of food additives (the Feingold diet), aspartame, coffee, and other foods as cures or causes of ADHD. Everything I learned back then was summarized in several journal articles and 2 books (Food Additives and Hyperactive Children, Springer, 1980; and Feeding the Brain, Perseus Publishing, 1989). What I learned from the Feingold/food additive controversy was the following:

Ben Feingold was an honest scientist and allergist with a sincere belief that Food Additives caused hyperactivity; a white-haired, persuasive charismatic figure who convinced thousands of his theory.
Just as he alleged, it was possible to "turn the hyperactivity on and off by giving or removing food additives." An effect we replicated in an ABAB design;
But all of the effect could be accounted for by placebo once a proper control group was added.
The only exception appeared to be for pre-school children where there was a slight indication that food additives increased hyperactivity (replicated by the Wisconsin group of nutritionists).

The power of placebo was strikingly illustrated by the very first child in our double-blind trial where food additve-loaded chocolate cookies were compared with additive-free chocolate cookies. On the first day of the trial the parent of the 6 yr old boy called, angrily threatening to sue us: "I don't know what you guys put in those cookies, but Kevin grabbed a knife and tore up our couch; he then took a hammer next door and destroyed the neighbor's motorcycle." Oh, oh...a looming court suit with big dollars flashed before me, but as fate would have it, you guessed it, he was on the placebo cookies. (Incidentally, this confirms Denny Cantwell's dictum that any red-haired boy named Kevin will grow up to be hyperactive.)

As Martin Orne once showed, the first thing a subject learns in an experiment is to obey what they think the experimenter wants to find.

Now back to feeding the brain. While at G. Washington and Children's Hospital in Washington DC, I carried out a number of experiments based on the Wurtman-Fernstrom hypothesis. They had demonstrated that a carbohydrate challenge elicits an insulin reaction which causes an efflux of large neutral amino acids (LNAA) from the blood, with the exception of tryptophan, which is lightly bound to albumin. Since LNAA cross the blood-brain barrier by competitive transport, tryptophan is given preferential input to the brain. Since tryptophan is a precursor for serotonin, the result is an increase in serotonin output, which is not regulated by positive feedback, so a burst of it can produce a sedative effect or other effects on the neurotransmitter systems.

We carried out several experiments in which we pre-fed normal and ADHD children with either a high protein breakfast, a carbohydrate breakfast, or a fasting condition, and tested them following a high level of carbohydrate beverage or aspartame placebo. An indwelling catheter was used to monitor hormonal responses, and tests of attention (CPT), cardiac response to warned reaction time (RT), and event-related potentials (ERP), monitored throughout the day. There were several results compatible with the Wurtman-Fernstrom hypothesis:

Baseline levels of carbohydrate were significantly higher in the ADHD than normals. (Judy Rapaport at the NIMH had reported no differences in serum carbohydrate levels, but the breakfast the children ate beforehand was not monitored, thus invalidating the results).
Attentional performance on the CPT (continuous performance task) and evoked cardiac response was impaired in the ADHD, but only when they had a carbohydrate breakfast, not a protein or fasting breakfast. The effect aoppeared to be in the early processing phase.
ERPs showed marked lowering of amplitude and slowed latency in the carb condition but only for the ADHD children.
Two hormones important in regulating carb levels (cortisol and growth hormone), were under-reactive in response to the carb challenge compared with controls.

I don't think we can conclude that high carbohydrate levels and increased serotonin cause ADHD. Instead, we propose that the recognized deficits in dopamine production or dopamine receptor function may be responsible for the hormonal effects, which in turn lead to a dysregulation of carb levels and the tryptophan/serotonin effect. This hypothesis has not to my knowledge been tested, and remains in my mind as an important future research problem.

Now, back to the fish oil issue. There is a small number of studies on the role of essential fatty acids (EFA), particularly omega-3, and ADHD, and some related areas like bipolar disorder and depression. In my next posting I will review this evidence. As a preview I can say that unlike neurofeedback and megavitamins, it is not the dictum of "Let the buyer beware" that applies, but the Scottish one, "Not proven."

My First Blog

2008-09-14T11:53:00.000-04:00

I retired from Duke 5 years ago, and it is with some trepidation that I launch myself back into the world of ADHD. When I retired I took Winston Churchill's advice to use oil painting as a past- time (paintings which readers can view on my Facebook website), but I find myself often thinking about ADHD issues and receiving queries from patients, parents and other strangers. I thought it might be useful to share some of these thoughts, and in future blogs here I plan to comment upon some of the perennial issues in this field:

Do foods, fish oil, additives, supplements, vitamins, etc. affect or cause ADHD?
Are there really as many ADHD children out there as are being reported in the media?
What are the important issues in the use of pharmacologic treatment of ADHD?
Is ADHD an evolutionary advantage of some kind? Is it truly increasing in the world?
What are the advantages and disadvantages of using rating scales in the diagnostic process?
What should we think about the big pharmaceutical companies in the world of ADHD?
Is there any role for sedatives, hypnotics, and tranquilizers in therapy of ADHD?
What ar some the myths about ADHD?
ADHD in schools: should we be concerned about how they are labeled and treated there?

In the meanwhile, I welcome any and all queries and comments from my colleagues, physicians and psychologists alike; as well as concerns and comments from parents or patients. I cannot of course give medical advice, but only my opinions based first on good science, and second on my own educated guesses acquired over my lifetime in the trenches of ADHD World. Join me!