Monday, November 24, 2008

Neurofeedback and ADHD: Save your money!

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.

Monday, November 17, 2008

Executive Function and ADHD

"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.

Tuesday, October 14, 2008

The myths of ADHD

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: 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.

Wednesday, October 8, 2008

How many ADHD children and adults are out there?

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 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 is the case 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 CANNOT MAKE A TRUE DIAGNOSIS.  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.

Wednesday, September 24, 2008

Science or Scam: Neuro-imaging for ADHD?

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.

Tuesday, September 16, 2008

Fish Oil as a treatment for ADHD?

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.)

Monday, September 15, 2008

Food and Behavior

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."

Sunday, September 14, 2008

My First Blog

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!