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Is ADHD genetic or developmental?
The art of medicine: only peripherally related to ADHD
Congressmen investigate ADHD drug shortage
ADHD Coaching
Short-acting ADHD medicine shortages in the news

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Dr. Kacir's ADHD Blog

Is ADHD genetic or developmental?

One of my patients asked the question in the title of this post.   He also asked if the genetic cause was a mutation.  After I answered him, I thought that my readers might be interested in my reply, so I have cut and pasted it below. 
 
ADHD is clearly inherited genetically since it is passed down from one generation to the next as reliably as height is.  It is a general rule that boys grow to be about 4 inches taller than the average of their parents' heights and girls to be 4 inches shorter.  In the case of height, there are known exceptions, some because of genetic issues (like dwarfism) and others because of developmental or environmental events like accidents or malnutrition.
 
Several genes have been associated with ADHD.  They are not mutations any more than brown eyes are mutations of green eyes.  The one gene that I remember is called DR4.  It is one of at least 6 different sequences that code for a Dopamine Receptor.  More people with ADHD have this particular gene than do people without ADHD.  However, not everyone who has this gene also has ADHD and not everyone with ADHD has this gene.
 
This is probably where the developmental part comes in.  It has been shown that young children have more symptoms of ADHD immediately after watching Spongebob Squarepants than they do after watching Sesame Street.  It is possible that young children who are exposed to a lot of electronic media might be more likely to have enough symptoms to be diagnosed with ADHD than children who spend a lot of time reading or playing with blocks.
 
There is also the fact that while only 4.4% of adults can be diagnosed with ADHD, about 50% of the population in prison can be so diagnosed.  This means more people who made the choice to do illegal activities (and got caught) exhibit ADHD than those who chose to obey the law.  Most of these choices are made during adolescence and can be considered "late developments."  It is clear that ADHD is associated with conduct disorder (a developmental issue that leads to problems with law enforcement) but conduct disorder can also occur without ADHD, so there may be reciprocal effects.  This would be another example of development affecting the expression of a genetic tendency to ADHD.
 
To summarize, genes are responsible for the possibility of having ADHD symptoms.  Environment and development probably determine whether an individual will have enough of those symptoms to match the full requirements of the diagnosis. There are
many genes involved and it is likely that certain variations of these genes are more common in ADHD.  Therefore if more of these genes are the ADHD type in a given person, then that person will have more symptoms of ADHD.

The art of medicine: only peripherally related to ADHD

I joined Linked-In a few months back and haven't quite figured out what it's good for, but they do send me interesting articles about health care, mostly from the business perspective.  I read two of these articles today and was somewhat amused to find that their views of medicine were near polar opposites... and both conflicted with my own. 
 
The first was written by "a former hospital executive and consumer health behavior researcher" with a Masters in Public Health.  His premise was that doctors need to change their view of compliant patients (who follow their advice and consult them about health choices) as being those with the best health.  His reason for criticizing this view is that some of the healthiest people around are those with a marked distrust of doctors and medicine. Those of them who nevertheless placed a high value on maintaining their personal health and devoted significant time and energy to relevant pursuits were more satisfied with their health status than were traditionally defined compliant patients.  The author suggested that all health care professionals (and he included himself as one) "incorporate the patient’s perspective into outcome and satisfaction measures."
 
The second article was an interview with Eric Topol—the chief academic officer at Scripps Health, who was touting the many digital diagnostic tools now available, although not yet approved by the FDA.  He urged doctors to educate themselves about all these technological gizmos and to start incorporating them into their diagnostic and therapeutic regimens.  Among the digital advances he mentioned were electrocardiograms with a phone, glucose levels via  touch screen and genomic sequencing to determine certain types of drug sensitivity for each patient.  He summarizes his conclusions as follows:
 
We need a Khan Academy for doctors: captivating 15-minute videos on genomics, on wireless sensors, on advanced imaging, on health information systems. These things can revive the excitement they felt as premeds, when they first decided to go into this field. If we can get practicing physicians up to speed and really inspired, maybe we won’t have to wait a generation. I shudder to think about waiting 10 or 20 years for this transformation to occur.
 
You can see that prioritizing the "digitization of medicine" over current practice, fails to take into account the patient's perspective touted in the first article.  Practically speaking, if the doctor is concentrating on the details and logistics of technology for diagnosis and monitoring, how much attention is left to listen to the patient's needs and desires?  Doesn't this focus further compound the skewing of outcome measurement toward the goals of the health industry rather than those of the individual patient?
 
My personal perspective on the digitization issue is that it has nothing to do with the excitement I felt as a premed.  My goal was to have expertise that allowed me to help people to feel better after our interaction than they did beforehand.  The more experience I gained, the more apparent it became that the most important diagnostic tool I had was the ability to listen.  At times, that ability is the most effective treatment available as well.  Digital media give me more data to interpret, change the way I record my actions and add to the information I can convey to patients, but they do not help me to empathize or communicate.  Those skills are what will lead my patients to feel better... and that is the outcome I seek, regardless of how it is measured.
 
In my ADHD practice, evaluation and treatment is based almost exclusively on my patients' impressions and reports.  The goals of therapy are the goals described by my patients for themselves.  I try to stay current on the technologies available to help them, but I rely on their expertise in their own experience to inform the process we go through.  The success of my practice is the outcome measurement I use, so perhaps I am utilizing my patients' perspectives for such measurements after all! 
 

Congressmen investigate ADHD drug shortage

CQ Roll Call, a subscription service reporting on congressional activity reported that 4 House Democrats wrote inquiries to the DEA, Shire (the producer of Adderall, AdderallXr, Intuniv and Vyvanse) and Novartis (the maker of Focalin and FocalinXR).  The inquiries explore the allegation that the two companies are making too much of the more expensive brand name drugs and not enough of the generic form with the amount of raw materials they are allowed by annual regulation.
 
I think they are asking the wrong question of the DEA.  There are several smaller companies that ONLY produce generic medications... and usually at a lower price than the generics from big companies.  Why hasn't the DEA funneled more of the raw materials to those companies?  More importantly, why haven't the quotas increased with the increase in prescriptions for these medications?  It is estimated that 4.4% of the U.S. adult population has ADHD.  Five years ago less than 10% of these people were being treated.  I saw a more recent estimate of 30% -- that's a lot more prescriptions!
 
Expensive though they may be, Big Pharma companies operate in a free market. Novartis and Shire risk alienating their customers who prefer their generic products if they are indeed funneling their allotted materials into name brand medication.  In the case of Vyvanse, there is no generic equivalent and in many cases, Vyvanse is a better medication than generic Adderall or Dexedrine with which it shares an element of the raw materials.  Vyvanse is usually smoother acting, lasts longer and has less of a let down at the end of the day.  It is also the least expensive of the brand name medications.
 
The congressional inquiry is a good idea so that it may publicize decisions made by the DEA and pharmaceutical companies.  It is my opinion that the basic problem is that regulations have not kept up with the medical need for controlled substances.  Brand name pharmaceutical companies have behaved in a manner befitting private industry, maximizing their profit margins, but this does not account for the shortages of brand name Adderall.

ADHD Coaching

A couple of years ago, I was talking to a friend who was dealing with her own ADHD and that of her children.  She had found a great ADHD coach and recommended that I hire her, too.  Life interfered, and I never got the referral information, but I've always remembered her glowing recommendation.  I have read about coaches online, but have not yet met one in person and I have hesitated to recommend them to my patients due to my lack of experience.
 
Today, I got a LinkedIn message that inspired me to do some research.  I found two local ADHD coaches who seemed to have good credentials and a link to this article: http://www.additudemag.com/adhd/article/4002.html.  I was very impressed by the article and thought I would share it with my readers!

Short-acting ADHD medicine shortages in the news

The New York Times and The Boston Globe both ran articles about the shortages of generic ADHD medicines on New Year's Day.  The Times described a tug-of-war between the FDA and the DEA regarding its cause...and even its existence!  A spokesman from the DEA stated that there were plenty of ADHD medicines.  He went on to say that the problem was that manufacturers had chosen to make more brand name medicines rather than funneling their allotted active ingredients to the cheaper generic drugs.  He did not address the fact that companies which make only generic medicines suffered equal shortages nor did he acknowledge the shortages of brand name versions as well.
 
According to the articles, the DEA believes that the increased demand for Adderall is principally abusive.  One statement described college students taking the pills to stay up all night and liking the sensation so much that they continued to use it after they graduated.  Another DEA spokesman cited the ongoing shortages of non-controlled generic medications as being evidence that DEA regulations did not contribute to the shortage of controlled generic medicines.  (Manufacturers of "old fashioned" generic injectable medicines have stopped making them in favor of newer medicines that bring in more profits.  This is causing problems in hospitals since the "tried and true" remedies are often safest and most effective for the majority of patients.)
 
The Food and Drug Administration (FDA) on the other hand, has been fielding dozens of calls every day from patients who cannot get their legitimate prescriptions filled.  Spokesmen from CHADD and an organization of child psychiatrists both cited serious problems for patients who risked school failure, car crashes and job losses without their prescribed medication.
 
Personally, I am conflicted about the issue.  On the one hand, there is a big problem with the abuse and misuse of stimulants.  Regulation by the DEA and DPS is necessary at all levels: manufacturers, distributors, pharmacies, prescribers and consumers.  The short-acting generics are more likely to be abused than are the more expensive, longer-acting medications and so there is some justification for limiting the availability of the short-acting substrates.  On the other hand, some patients simply cannot afford the higher priced pills with better availability.  There are also patients who  do not tolerate the longer acting medicines and others for whom they do not work as well.
 
The good news is that regulations have allowed for more medications to be available in 2012 than were present in 2011.  It remains to be seen whether the increases are sufficient to prevent any shortages... and whether abuse becomes more common.  It will be interesting to review the investigations of stimulant misuse and abuse.  Which side of the controversy would be supported if the number of reported violations was significantly lower than expected?

The source of attention

In a review of a new book about the neuroscience of attention, I read a terrific definition of what attention actually is.  The review began as follows:
 
"William James once wrote: 'Everyone knows what attention is. It is the taking possession by the mind, in clear and vivid form, of one out of what seem several simultaneously possible objects or trains of thought.'
 
I was very impressed and wracked my memory to figure out who William James was.  The father of modern medicine?  No, that was William Osler.  A great writer with psychological insight into the human condition.  No, that was Henry James.  So I did what my high school age kids do -- I went to Wikipedia.  Wow!  William James was identified as an attorney and naval historian from 1813-1827.  What a great cross-field reference.  To think that an analysis of military actions could produce a cogent definition of a psychological term!
 
Then I realized that I had skipped a step in my "research," so I googled William James.  Darnitall.  It is far more likely that the reviewer was quoting "a pioneering psychologist and philosopher who was trained as a physician."  To soothe my ego a bit, however, it turns out that Henry James was his brother.  Reading his Wikipedia entry does reveal quite a bit of additional cross-field pollination.  Ralph Waldo Emerson was his godfather and he interacted with Bertrand Russell, Mark Twain and Sigmund Freud.  While he was a professor at Harvard, Gertrude Stein and Theodore Roosevelt were both his students. 
 
To bring it all back to the subject of attention, Gertrude Stein actually did some research in the field under James' supervision.  Thus from this blog entry, you can see the anatomy of distraction.  My original intent was to include a brief paragraph about a non-scientific reflection on attention's nature and it has turned into a treatise with elements of literature, art, history, philosophy and politics.

Treating ADHD in jail

I just finished reading the summary of a study in which male prison inmates with ADHD were treated with Concerta.  This is a useful study because ADHD has been shown to be very common in convicts.  While the prevalence of ADHD among
U.S. adults is 4.4%, it is over 50% in the prison population!
 
This sudy was well designed with 5 weeks of double-blind-placebo-controlled research, followed by active treatment and open evaluation for an additional 47 weeks.  Inmates were assessed for symptoms of ADHD and their global functioning on a regular basis throughout the year.
 
There were no significant adverse effects during the course of the study, nor was placebo found to be effective.  Treated inmates showed a marked reduction in their ADHD symptoms and reported significantly improved functioning in their daily activities during the first five weeks.  These positive results continued to improve over the non-blinded extension of the treatment.
 
The conclusion of the authors of this study was that Concerta was an effective treatment for prison inmates with ADHD.  It would be even more significant if treated inmates were found to have less negative behaviors than their untreated peers, were eligible for parole earlier and were less likely to return to jail after release.  Findings such as these would justify ADHD treatment at taxpayer expense.

TV and 4-year-old executive function

Since finishing ADHD and the Nature of Self Control, I hadn't found any new and interesting articles to describe until today.  This is an article in Pediatrics: a monthly peer-reviewed journal for Pediatricians.  Previous research has seemed to indicate that more television-watching by children leads to more attention problems.  The evidence, however, is mostly observational and does not indicate exactly how attention is affected by television.
 
The authors of this study thought that the problem could be the fast pace of images in many TV shows.  When we see something for only a short time before it is replaced by something else, our brain spends its energy identifying what it sees each time.  This takes place in the sensory part of our brain, not in the pre-frontal cortex, where the brain prioritizes our attention with executive function.  If this is the way that the rapid change of scenes on TV caused attention problems, then executive function should be worse after watching them than after doing something else.
 
To test their theory, they recruited sixty 4-year-old children and divided them into three groups each of which was assigned to a different activity for 9 minutes.  The first group watched a cartoon about "an animated sponge" with complete scene changes every 11 seconds.  The second group also watched a TV show, but this one was from PBS and changed scenes every 34 seconds.  The third group was given paper, crayons and markers and told to draw freely. 
 
Each child pursued their activity in a separate room and after the time was up, the researcher tested their executive function.  They used standard activities which measure verbal and non-verbal working memory, spatial planning and delay-of-gratification. 
 
The result was that the group which watched the fast paced cartoon scored significantly worse than either of the other groups.  I was surprised that those who watched the PBS show scored better than those who colored on two of the tests, but it is good news for those of us who support Public Television for kids!
 
This study gives new information about the effect of different activities on the 4-year-old brain.  At least at this age, exposure to rapidly changing sensations interferes with the ability to process more complicated information.  It would be interesting to see the results of a similar study on adults with and without ADHD... I think that similar effects might be shown and would be more pronounced if ADHD were present.

Summary of the Barkley book

I finally finished the book I've been working on for so long and I'm pleased to say that I have gotten a lot out of it.  I'm not sure it's what Dr. Barkley intended me to get, however!  As I have mentioned, he is a psychologist rather than an M.D., so he doesn't prescribe medication.  He very firmly believes in it, but his views on the nature of ADHD are colored by his expertise in behavior management and the descriptive nature of mental disorders up to the last few years.  He recommends psychological counseling in addition to medication in every person with ADHD.  Furthermore, he is in a large academic center, so he aims to make recommendations that can be supported by peer reviewed research.
 
As I understand them, these are his new theories about ADHD:
1. It is a disorder of behavioral inhibition, not primarily a problem of attention.
2: The disorder is a delay in the usual pattern of learning to control one's behavior.
3. The usual pattern is an internalization of the external cues/environmental feedback that initially govern children's behavior.
4. Primarily inattentive ADHD may be an entirely different disorder.
 
I disagree with #1, primarily because I disagree with #4, but I think that his emphasis on inhibition rather than attention is not entirely wrong.  As I may have said before, I feel that the basic problem in ADHD is a failure to stop an automatic response to a distraction in order to stay attentive to what one is doing.  If that response is an action, then it is a failure of behavioral inhibition.  However, if that response is only a change in one's focus it is a failure of attention.
 
If one adds "and attention" to #2 and #3, I actually agree with them.  I don't agree with Dr. Barkley's following suggestion that different behavioral analysis be performed for different age groups.  I think that the current symptoms can be adapted by the diagnostician to each patient's developmental stage.  #3 gives a very practical suggestion to treat ADHD, which Dr Barkley acknowledges, but does not emphasize as much as his opinions about changing diagnostic and research strategies.  Essentially, the person with ADHD can "re-externalize" behavioral/attentional controls.  Specifically, one can replace the internal time sense lacking in so many people with ADHD by utilizing timers and cell phone alarms.  Written lists replace faulty working memories and rewarding oneself for each completed task with a tangible consequence can enhance self-motivation.
 
The end result of reading Dr. Barkley's book, ADHD and the Nature of Self Control was that it solidified some of my impressions about the nature of ADHD.  It also gave me a lot of food for thought and some practical information for my patients.

Long time, no post.

I had been trying to post on the blog much more frequently than this, but I am shocked to find that it has been 2 months!  The office has been very busy -- but that has been because I have taken several short vacations and I have had to "squeeze in" appointments when I have been here.  The major reason for my silence has been a lack of inspiration -- I am still reading the book by Barkley to which I referred on May 31.
 
I finally found another issue which struck me as worth posting about.  It is in the portion of his book where he is predicting the likely problems which will result from ADHD if, as he has proposed, the disorder is primarily a delayed ability to stop immediate responses to environmental stimuli.  (He denies that these "predictions" have stemmed from actual observations of people with ADHD rather than coming only from his hypothesis and the evidence with which he supported it. Personally, I don't see how his years of experience in evaluating children and adults with ADHD can help but inform these predictions, but I won't argue the point any further.)  After he predicts "Diminished and Disorganized Verbal Thought," he addresses "Impaired Self-Regulation of Affect/Motivation/Arousal."
 
I was intrigued by his mention of motivation, as some of my patients state that their lack of motivation is one of the aspects of ADHD they find most frustrating.  One parent complained that her teenage son didn't seem to like doing anything and that she was hard pressed to reward good behavior, since there was so little he regarded in a positive light.  This worried me and I examined him carefully for signs of depression, but he had no other symptoms suggestive of it.  An older patient came in to resume treatment after being off of medication for some time.  He complained that when he was unmedicated "I just didn't want to do anything!"
 
Barkley suggests that a lack of self-motivation results from the difficulties with remembering emotional states associated with previous similar situations.  (Remember the executive functions of self-regulation and working memory.)  Because a person with ADHD has trouble calling to mind previous rewards from a given activity, he or she is less likely to repeat that action unless immediate positive feedback is anticipated.  The actual wording is as follows: "By being less capable of mentally representing and sustaining internal information about prior contingencies, those with ADHD are less able to reawaken their associated affective and motivational states.  This should create a condition in which those with ADHD are unable to covertly emote to  and motivate themselves....  and so remain dependent on external forms of immediate reinforcement in order to persist at tasks and activities and to defer gratification."  (You can see why it's taking me so long to read his book.  Every paragraph is like that.)
 
It was gratifying to be able to apply his complex prediction to my simpler model of ADHD.  Essentially, the problem in ADHD brains is that they cannot always stop the automatic shift of attention that occurs for every sensory event.  The message to do so is sent, but does not get through.  More messages are sent (and thus one of them will be more likely to reach its goal) if positive reinforcement is anticipated for sustained attention, or if negative reinforcement will result from distraction.  When a brain does not efficiently recall previously felt emotions, it cannot anticipate either good or bad results and no additional messages will be sent.  A general lack of motivation then results from an inability to sustain attention to a situation long enough to predict a positive or negative outcome.  Such prediction may be even less likely in a person with ADHD since they cannot easily "relive" previous similar situations.
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