Behaviour in PWS - where? What? Why?

by Linda Thornton

In .52 of a second, Google furnished me with a choice of 158,000 articles on behaviour in Prader-Willi syndrome.  It is overwhelming and if I were a new parent, I would not know where to start.  In fact, I probably would yell at Google, close the page and burst into tears.  There are scholarly articles, there are profiles of behaviours, advice on managing behaviours of pre-schoolers, toddlers, pre-teens, teens, adult and so on.  After 20 pages of Google and in amongst all the PWS articles,  suddenly I find a page on growing marijuana and by this stage, I’m thinking “what a good idea!”

Personally, I think that finding a PWS Association either online or in reality, is the best possible thing to do.  To be able to talk to someone face to face, or on the phone, or even just an email, will result in a calmer, easier-to-understand answer than trying to assimilate information from 158,000 different articles.  That’s just frightening.

The best possible thing you can learn about behaviour and PWS is that children and adults are all different.  They are people first, and just happen to have Prader-Willi syndrome.  Knowing your child, what motivates them, what they love and who they love, what scares them, what makes them anxious, and so on, is the first step towards understanding behaviour.  When you stop and think about it, everything we do, from getting up in the morning to going to bed at night, invokes behaviour of some kind or another.  Our behaviour sends messages to others in many different ways – no matter whether we have a disability or not.  It’s how we interact.  

I’ve watched the behaviour of my 32-year-old over the years and can read her like a book.  But I can also do this with my other children as well, the only difference is that my 32-year-old has more pages in her book.  That’s life.  Whether her behaviour is challenging, whether she’s testing whatever system that’s been put in place, or whether it's her every-day behaviour, for me the most interesting thing is how she interacts with other people.  I used to worry that she would ‘snap’ if someone said or did the wrong thing – and by this I mean a stranger, not someone she is familiar with because the more familiar she is with someone, the more likely she is to let loose! 

The other day, for example, I listened to her on the phone to her bank.  She was polite, very clear in her request to transfer funds and knew exactly what she was talking about.  She quickly and efficiently changed one automatic payment into another.  No problem at all.

I’ve heard her ring and make a doctor’s appointment; phone the library and request a particular book; she manages a visit to the Vet with her cat perfectly well and asks all the right questions and makes sure she knows the answers.  In an emergency (her concept of one) she will get herself down to the Emergency Department at the local hospital (with a staff person) and wait until she can be seen.  She knows when she is ill (see previous blog on gastroenteritis).  By being able to do these things she avoids becoming anxious, frustrated, and angry.  It has become so clear to me over the years that by first teaching her about making good choices, she is able to do so much more for herself.

Sometimes, in the middle of a catastrophic outburst I tend to forget everything I’ve just said above and feel as though I’m clinging to the life-raft for all I’m worth.  Just getting through to the other side of the meltdown is all I’m hoping for at this stage!  I hate it when these happen because I know how terrible it is both for her, and for the person she is focussed on.

I began to wonder what sort of chemical imbalance might be in place when these meltdowns got under way.  So I asked Tony Holland about this and about his research with vagus nerve stimulation.  He responded,

"Our work on vagus nerve stimulation suggested that people with PWS essentially have a a low threshold for such outbursts and also impaired emotional control - in other words people with PWS are easily triggered and once it starts such an outburst more easily builds up and leads to loss of control when compared to people without PWS. This appears to be improved by vagus nerve stimulation. The vagus nerve is part of the autonomic nervous system of the body that manages our response to threat - what we think vagus nerve stimulation is doing is normalising that response. The other rather different issue we are beginning to look at are two chemical (neurotransmitter) systems in the brain - GABA and glutamate - the former is inhibitory and the latter, excitatory. It may be that an imbalance of these two systems is important - a new study we are starting uses brain imaging to explore this hypothesis"

So, although I know that there is much behavioural research going on with Oxytocin* (Google: 1.10 seconds, 115,000 articles) and the Vagus nerve stimulation** (Google:  .72 of a second, 60,600 articles), I can’t help but think that deep down it pays to really understand your child and what makes them tick.  You may be surprised.

 (If you would like help with behaviour issues and would like to talk to our specialists about this, please email us)

*Maithé Tauber Oxytocin research

**Tony Holland Vagus Nerve Stimulation

Summary of some Scientific Conference talks

 

Contributed by Dr Janice L. Forster, IPWSO Clinical Scientific Advisory Board; Child and Adolescent  Psychiatrist in private practice in Pittsburgh, PA who specializes in Developmental Neuropsychiatry.

Dr. Jeremy Veenstra VanderWeele presented an overview of autistic spectrum disorder (ASD) and discussed the complexity of developing biomarker-based therapeutics that produce change in behavioral domains in complex syndromes.  He spoke about potential targets of interventions from genes to proteins to networks that are developmentally expressed to impact neurons, synapses, specific  brain regions and interconnecting circuits in the brain.  He described how difficult it is at times to determine whether changes that are observed or measured to occur during treatment are actually due to the treatment intervention.  He discussed medication trials in complex syndromes that were effective and not effective. Risperidone, which improves irritability/agitation, hyperactivity/defiance, and stereotypic behavior in ASD, is offset by side effects of weight gain, extrapyramidal signs, and metabolic changes leading to insulin resistance.  A similar drug, lurasidone, was ineffective.  A trial of citalopram to target stereotypic behavior in ASD was ineffective, but produced side effects of mood activation in 50% of study participants. Overall, when co-morbid disorders are attached to ASD, treatment response is diminished and side effects are more likely to occur. All of this experience of developing drug treatments for autism can be applied to PWS.  

Dr. Eric Hollander and his colleague Dr. Bonnie Taylor presented their preliminary findings about an 8 week, double blind placebo controlled trial of oxytocin in PWS. This study defined target symptoms of repetitive behaviors using the Repetitive Behavior Scale and Yale Brown Obsessive Compulsive Scale, disruptive behaviors using the Aberrant Behavior Checklist-Irritability domain, and social communication using the Aberrant Behavior Checklist-Social Withdrawal domain and the Social Responsiveness Scale. These assessment tools worked well. The data obtained were preliminary findings as the study had not concluded, and the blind had not been broken. None the less, they presented the data as responders and nonresponders, even though they did not know who was actually receiving the oxytocin. This drew criticism from both parents and scientists. This presentation was a reminder of the value of placebo controlled studies and the importance of understanding placebo response in PWS.

Sleep was a theme explored  in animal models (Necdin, Magel2, and SNORD116 deficient mice) during the scientific conference. Technology now allows for sleep studies, similar to those performed in humans, to be studied in mice. These animal models are contributing to our understanding of the genetic underpinnings of disrupted sleep in PWS (increased sleep cycles, increased fragmentation of REM sleep with intrusions into daytime, and impaired timing of anticipatory behaviors) and whether there are medications that can rescue these abnormalities. One must be careful to realize that these findings occur in specific genetic models of PWS and may not be generalizable to humans.  During the pre-conference workshop, which occurred on Wednesday, there was a discussion about the impact of both disrupted sleep and abnormalities of wakefulness and their impact on cognition, mood and behavior in PWS. In the scientific session  Dr. Holger Stark presented his studies in Europe using histamine 3 receptor antagonists to enhance alertness in narcolepsy and Parkinson's disease.  With a favorable side effect profile, he was optimistic that this class of medications might be helpful in PWS.  

Finally, there were some fascinating presentations regarding diets and pathways to obesity in all of us.  Dr. Mark Friedman presented Hyperphagia: Cause or Consequence of obesity. He described evidence of abnormalities of fatty acid oxidation in liver cells, leading to increased deposition of fat, increased glycogen storage, decreased available energy, resulting in hyperphagia. For them, high carbohydrate diets promote lipid synthesis and storage while inhibiting fatty acid oxidation and mobilization. These individuals have a decreased ketone response to a fast and intolerance of low carbohydrate, calorie restricted diets. They require diets with higher fats and lower carbs but not calorie restriction.  His work debunks the myth that obese people are fat because they eat too much.    

Conference: Day 1

From our Japanese children

The first day of the conference started with the Scientific presentations and, alongside this was the Caregiver Conference.  I am simply not able to report on everything (but there will be a report on the conference at a later date), so this blog will just be me talking about the things I have heard and seen.

Although the Scientific conference is always the first place you look to for any new developments, my first interest is always to do with how we can best manage and care for those with the syndrome.  Today I sat in on two of the scientific presentations that interested me, and the rest of the day was with the Caregivers.  The presentation "Can Oxytocin Help in Prader-Willi Syndrome" was of interest to me because of the studies being done to see whether oxytocin, in the form of a nasal spray, will help to modify "behavioural temper tantrums, perseveration, obsessive compulsive behaviours, manipulative conduct, sudden aggression and abnormal food seeking".  Thirty-one participants enrolled in the trial conducted at the University of Sydney, Australia.  Eight participants completed the trial with a lower dose; 17 participants completed with a higher dose.  The age ranged between 12 and 30 years and participants were selected because they had difficult or challenging behaviours.

Behaviours were evaluated daily by a primary caregiver:  hyperphagia, temper outbursts, skinpicking, obsessive and compulsive behaviours and under-reaction to pain.  At the end of each phase the carers also completed questionnaires about the individuals' general behaviours, sleep patterns, social skills and emotional liability.

After all the clinical trials were completed, the answer to the question, "Can Oxytocin help in Prader-Willi Syndrome" was, (and I quote) "No."

Apparently there were no differences noted in any of the above behaviours.

I guess this is disappointing since we all hope for something that will help those with PWS to be less ruled by their behaviours and become happier people, fitting into society.

After that, I sat and listened to part of the Caregivers Conference where a lovely young man called Aneil who lives in a residential setting here in the UK spoke with his caregiver about his life.  These are some of thing things he told us:

• Know and understand me.  
• Don't label me, I am individual.  
• Listen to me and advocate for me.  
• Prioritise the things that are important TO me and be realistic about what is important FOR me.

Somehow it always helps the balance of things to actually hear from the people we are always talking about!

.... More tomorrow!

Linda