Medications for childhood behavioral disorders: What are the effects?

Guanfacine is an old medication for hypertension, marketed as Tenex. It's thought to act by stimulating alpha2-adrenergic receptors in the brain; in other words it's an alpha2-adrenoceptor agonist.

It's not a great antihypertensive and it's not used much for blood pressure treatment any longer. It is used, off label, for the management of some behavioral disorders in children.

What effect, I wondered, might it have on the developing brain?

It wasn't hard to find this on Pubmed.

Activation of alpha2A adrenoceptors alters dendrit...[Brain Res. 2008] - PubMed Result

Activation of alpha2A adrenoceptors alters dendritic spine development and the expression of spinophilin in cultured cortical neurones.

Hu J, Vidovic M, Chen MM, Lu QY, Song ZM.

Division of Neuroscience, John Curtin School of Medical Research, and Medical School, Australian National University, Canberra, ACT, Australia; State key laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060 China.

alpha2 adrenoceptors have been shown to regulate the development of dendrites in mammalian cortical neurones. In this study we have investigated how agonists of alpha2 adrenoceptors affect length and density of dendritic spines in cultured cortical neurones from C57/B6 mice. A twenty-four hour incubation of 14 day old cultured neurones with UK 14304, an alpha2-adrenoceptor agonist, resulted in a significant increase in the average length and density of dendritic spines. Furthermore, incubation of neurones with the selective alpha2A agonist guanfacine resulted in 1.2-fold increase in spine length and 1.8-fold increase in spine density. These effects were blocked by RX 821002 and BRL 44408, alpha2- and alpha2A-adrenoceptor antagonists, respectively. The observed changes in the density and length of dendritic spines were correlated with increased expression of spinophilin, a key cytoskeletal protein in the formation and maintenance of dendritic spines, and a decrease in the phosphorylation of spinophilin on serine residues. The latter finding points to a possible mechanism by which adrenoceptors may regulate spinophilin function in dendritic spine development and structure in cortical neurones in vitro.

It seems likely then that Guanfacine alters the course of neuronal development in humans, as it does in mice.

So, is this a good thing, or a bad thing?

We don't know.

There's a lot here to think about, on several different levels.

How do you manage a broken brain? We don't know.

How do you manage a broken brain?

What do you do when some skills are at the 75th percentile, and others at the 2nd percentile?

Much harder -- when some skills are at the 4th percentile, and others below the 1st percentile?

Do you create a profile of all the strengths and weaknesses, a visual representation to analyze and evaluate? An MRI of the mind?

Do we create programs to strengthen the weakest areas, or do we leverage the stronger domains? Or perhaps the middle range?

Can two or three areas of strength be combined to help an area of weakness? What role might cognition-medications have? What role do psychostimulants have?

How do we measure progress? How do we know when to change direction?

How do we intervene in infancy, when surgeons can remove half the brain and a child can still go to college? In early childhood? In pre-adolescence? During the teen years? In adulthood? In old age?

How do we leverage computerized, robotic, and remote human aides to support severely impaired cognitive functions?

We flippin' don't know. We're barely at the starting line. We don't have any science-based plans. Opinions, yes. Science, no.

It's not surprising. We know far more about kidneys than minds, and we don't really know how to manage an injured kidney. Is physical exertion good or bad? How low should the blood pressure be? Proteins good or bad? Which proteins? ACE inhibitors?

We're in the stone age of managing broken brains -- little improved from the best practices of the past 10,000 years of human history.

I can imagine ways to start to make progress. Ways to study developing brains and minds. Ways to create comprehensive profiles of strengths and weaknesses and use those profiles in discussion and analysis. What I can't see is how to make significant progress in my lifespan with the available political will and funding.

Anyone know a billionaire with a cognitively disabled child?

Autism spectrum disorders on the phone: would a webcam or mirror help?

I wonder if this technique would be helpful for people with autism spectrum disorders. Would seeing their own facial expressions help with self-evaluation and self-assessment?

Gordon is using a webcam, but a mirror would also work...

Gordon's Notes: using a webcam to help with audio-only conference calls

... I've recently been persuaded that for many people, including me, even crummy low resolution images enable better social interaction and higher quality communication.

So I've started using a webcam with Office Communicator 2005. Unfortunately the people I communicate with don't usually have a webcam, so it's one way. They see me. I either see a blank space or my own face.

That's where I made an interesting discovery. It helps me, when on a phone call, to see my own face. It helps me be more patient, and even to be a better listener....

So I'm experimenting with viewing my own face and body language when I'm on voice only calls. I'm guessing it will help me be more conscious of my own reactions, and better able to manage the call....

Autism Society of Minnesota: Recommendations, PCA infrormation

We've been taking "Sam" to the Eagle's Nest social skills program at the Autism Society of Minnesota. I think it's somewhat helpful for him [1], though it's designed more for children like Sam's brother "Nick". Nick is up next, though that will take a carefully coercive mixture of bribes and consequences.

The real value for us though has been the parents session led by an expert counselor with serious personal experience with "the spectrum". The "AuSM" also has q1-2 week skillshop topics and an excellent member's only Lending Library (click to browse collection): "Library materials are available for loan to all current AuSM members. You may check out up to 6 items for 3 weeks at a time."

In particular we've been learning more about schools (Junior High looms in 1.3 years), SSI, and PCA services.

Form what we've learned and seen there's no simple Junior High answer for "Sam". We have, however, learned of arrangements that will work for "Nick", such as leaving classes 2-3 minutes early to avoid the hallway pandemonium. For "Sam" we need something more like Lionsgate, which is massively oversubscribed even before it's operational. We're thinking hard.

Beyond High School are programs like Minnesota Life College (private, $$), school district "transition services", and SSI (social security disability).

The SSI bit is important for all children with developmental disabilities. Most will need to apply for SSI disability on their 18th birthday (if not earlier). Apparently if one waits too long to apply for SSI some "window" for developmental SSI closes, and one is eligible only the American's ridiculously small standard SSI ($370/month - enough for heat maybe).

Which brings me back to the PCA (personal care attendant) topic. The AuSM has an excellent handout called Services for Children with ASD (scan PDF 103K) I'll summarize here and expand upon:

• TEFRA: medical assistance, but qualification based on disability. If a child is on Medical Assistance (ex: foster adoption) or qualifies for SSI (disability) they don't need TEFRA. TEFRA has a family fee. TEFRA will help pay for PCA Services and Waivered services.
• PCA services (see esp MN PCA Choice Option). If two children in a family qualify an incremental amount is available above the usual family rate. (See also my PCA comments, below.)
  
• Waivered services (see MR/RC (mental retardation) waiver and CADI waiver). The CDSC waiver option (consumer-directed community supports) "parents of minors may be paid for daily care tasks." This has a special appeal for us (below).

The CDSC waiver option is where we want to go. We've had PCA services for "Sam" for years (see also: PCA things I wish I'd known), but have never applied for services for "Nick" -- though he would probably qualify. Over this time we've followed the conventional route of engaging an agency who takes a substantial cut of the stipend and is supposed to do background checks, training, hiring, etc. This hasn't always worked out well, and with the departure of our latest PCA we're resolved to do something differently.

Our special challenge is that Sam makes everyday high functioning autism look simple by comparison. We need a PCA with vast patience, creativity, affection, empathy, physical durability, training athletic capacity, maturity, reliability, and knowledge of swimming, golf, fishing, paddling, horseback riding, bicycling, inline skating, hockey, ice skating, skiing/snowboarding, and baseball (latter at a high school level). Experience with autism, ADD, EBD, ODD, and anxiety disorder a plus. Must be willing to work for very little money on weekends and nights.

I think the problem is clear. Sam needs his parents to manage him -- nobody else can do that.

So, what we need is an extra set of hands, with a secondary focus on helping Sam's sibs, including a neurotypical child. A nanny with a bit of special needs experience, or just empathy and wisdom, would do very well. If we could get a CDSC waiver we'd be able to the money paid "us" to buy services for the entire family -- freeing up time and energy to keep all the balls in the air.

So that's our latest project. As we push that along we've also learned of two recommended PCA agencies for waivers and other variations and a woman who works as a "Flexible Case Manager" (a role that may be related to the waiver programs.)

• LifeWorks customized support services: "A shift in funding in Minnesota in 1999 gives people with disabilities and their families more control over the services they receive. Lifeworks’ Customized Support Services (CSS) offers the Agency with Choice and Fiscal Support Entity services required for families to access these waivered funds. This allows children to continue to live at home, gives families the freedom to live a more normal life, and saves money for Minnesota taxpayers." I'm told a typical cost might be $175/month for their services.
• St. David's Child Development and Family Services (Minneotonka): "St. David’s offers an additional service option that individuals or families can choose under the PCA program model called PCA Choice. For this service option, the client or family is responsible for interviewing, hiring, training and supervising any staff. The individual or client enters into a written agreement with St. David’s for billing and payroll services."

[1] Sam almost does very well in these settings. It's unstructured settings where the challenges come out.

Berate, Guggenheim and ABC: three slimy entities

There's no good reason today to believe that autism spectrum disorders are related to immunization.

Science in general, and clinical science in particular, is very imperfect. Even so, it's all we've got. There are no credible competitors to science for guiding health care and health related decisions.

The answer from the best science we've got is that there's no connection. The strong beliefs of many people has meant that the topic has been very well studied -- probably to the detriment of more promising investigations. Today what was once a plausible hypothesis has become a waste of time and resources. We have better things to do now.

Maybe that situation will change, but today that's what it is.

So, like all scientists and most clinicians, I was very annoyed when I heard about a television show promoting an autism/immunization link. Still, that's what one gets from television. There's a reason I don't watch it.

What took me from annoyance to blogging, however, was this quote from the creators of the TV show:

ABC defends show against outcry by pediatricians: Scientific American:

....ABC said it plans to broadcast the episode without changes, but would run a disclaimer at the opening of the show stating the story is fictional. A message at the end will refer viewers to a CDC Web site for information about autism.

The show's two creators, Greg Berate and Marc Guggenheim, disputed the notion that their show would frighten parents away from vaccines.

'We actually share the concern of the American Academy of Pediatrics. We believe that children should be vaccinated,' Berate told Reuters. But he also said, 'We hope that people do watch the episode and draw their own conclusions.'...

That's slimy. If they really believe that immunizations lead to autism, they should have the courage to say so. If they believe otherwise, then they're cynical slimeballs to have created the show. "Disputing" the notion that the show discourages immunization makes my head explode.

Whatever the explanation, whether they're believers or not, they are definitely slimy -- and so is their network.

I'd boycott ABC, but I already mentioned I don't watch television. Maybe I should watch NBC so I can say I'm boycotting ABC, but that's too terrible to consider.