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.
