Behavior and mental health issues are important aspects in Prader-Willi syndrome (PWS), impacting many individuals with the syndrome and their families. In particular, one of the most challenging aspects for families to deal with can be symptoms of serious mental illness such as psychosis (i.e., mental illness characterized by symptoms such as delusions or hallucinations). The rates of occurrence of delusions and psychosis in PWS is higher compared to the general population, especially for those with uniparental disomy, according to studies by Larson, et al., and Yang, et al. In this regard, people with PWS are considered to be at high-risk population.
Most research in the area of mental health, both in the general population and in individuals with developmental disabilities, has focused on identifying symptoms of illness and finding effective treatments. But mental health researchers are now starting to focus on the early detection and possible prevention of the onset of serious mental illness, especially for people who are identified to be at high risk, as discussed in this article published in Science Magazine in November 2017.
New Focus on Prevention in Psychiatry
Psychiatry is one of the few areas of medical specialty that has not focused on prevention until recently. There are a few factors that likely explain this. One is the stigma of mental illness, which is a powerful barrier to prevention. The other is that the brain in an extremely complex organ. But in the last few years important work is underway focused on prevention. Last fall, a German pharmaceutical company started a large randomized clinical trial testing an experimental drug to prevent psychosis in people at high risk. It’s believed to be the first time a company has poured millions of dollars into an effort like this.
Other prevention efforts are focused on non-drug approaches to preventing or minimizing symptoms of mental illness. Use of cognitive behavioral therapy (CBT) to help teens and young adults at high risk for mental illness reframe their thinking has been studied by Jean Addington and colleagues. Several studies of this specific type of CBT target high risk individuals in the general population, and have shown that CBT can ease symptoms of mental illness and reduce the risk of developing psychosis in the following year.
While it is exciting to see the increasing number of studies focused on possible prevention of psychiatric illness in the general population, research to date has not focused on prevention in individuals with neurodevelopmental conditions with high rates of psychosis and mental illness, such as PWS. But the tide is very recently changing. The first crucial step in this area of research is to determine how to detect the very early symptoms (i.e., prodromal phase) of mental illness in individuals with neurodevelopmental conditions, as these may be different from the early symptoms seen in the general population. While it is known that individuals with PWS are at high risk for developing mental illness and psychosis (Larson, et al. 2014; Yang, et al. 2013); very little is known about the early symptoms and the risk factors that might predict the emergence of psychosis or impending mental illness in PWS. This is a critical gap in knowledge given strong evidence that early intervention leads to improved outcomes in other high-risk populations. A project funded by FPWR is underway to examine this exact phenomenon in PWS.
Dr. Bearden Brings Prevention Mindset to Mental Health In PWS
Following her participation in the FPWR mental health research workshop a few years ago, Dr. Carrie Bearden, a UCLA researcher, started work on a project to better characterize the early (or “prodromal”) signs of mental illness and psychosis in individuals with PWS. Dr. Bearden’s project asks pre-teens and adults with PWS to complete carefully designed surveys geared to find the early signs of mental illness and, in particular, psychosis. These assessments examine memory, verbal and non-verbal reasoning, emotion recognition, and processing speed in individuals with PWS. Participants also provide saliva samples to measure the levels of hormones such as cortisol, for which an elevated baseline level has been shown in previous research to be associated with a higher occurrence of psychosis. Other information will also be gained from the saliva samples, for future analysis regarding early signs of mental illness. A little over 100 individuals with PWS have participated in Dr. Bearden’s study so far. About one-third of the participants have completed the entire study (all questionnaires and the cognitive battery). Dr. Bearden and her team are continuing to obtain data on the other participants.
Early analysis of Dr. Bearden’s data from this study show that about half of the sample have PWS via deletion, a third of the participants have uniparental disomy, and the remaining have imprinting mutation or the genetic subtype is unknown. There is a wide age range of participants in the study ranging from ages 10 to 49 years. Of the 87 participants who have completed the self or parent report screening questionnaire on early psychiatric and psychotic like symptoms called the Prodromal Questionnaire, about 40% endorse symptoms that reflect possible early psychiatric issues. Significant distress related to these symptoms was reported in about 1/3 of the sample. Among the symptoms most commonly endorsed were "holding beliefs that others would find unusual or bizarre" and "feeling that others are watching you or talking about you." These preliminary results suggest that unusual thinking and possible early psychiatric symptoms are reported for a significant proportion of teens and adults with PWS.
Participating In The Study
More data will help Dr. Bearden strengthen her findings and our understanding of prodromal symptoms in PWS, so if you / your child started the study but didn’t complete all of the surveys, or if you didn’t participate before, but would like to now, please complete the study here — it's all web-based.
The data collected in this study will be used to understand the multi-dimensional factors leading to psychiatric illness and possible psychosis in PWS. Identifying the prodromal (early) signs of psychiatric illness and psychosis in PWS will enable early intervention and treatment, which has been shown to result in significantly better mental health outcomes.
Once we can understand more about those individuals with PWS who may be at higher risk for impending mental illness, there are multiple forms of treatments to be explored to determine which would be most effective. The list of possible future avenues to research include anti-psychotic medication as well as non-pharmacologic approaches such as modified CBT, as mentioned above, and individual /family therapy techniques focused on stress reduction. Recognizing the early signs of psychosis is an essential and effective path to intervention and treatment. Dr. Bearden’s study is helping to lay this important groundwork.
Dr. Bearden and her team will be wrapping up data collection very soon, so if you or your child is a pre-teen or adult with PWS, please log on to the study if you haven’t done it yet, or if you started the study but did not complete it, you can log back in and finish. Through Dr. Bearden’s project and similar studies, we can learn more about the psychiatric challenges our loved ones with PWS struggle with and therefore have a guide towards reducing symptoms and possibly prevention in the future.
If you are interested in participating or finishing the study, please complete this enrollment form provided by Dr. Bearden or contact Ariana Vajdi, (310) 825-3458.
Learn more about PWS mental health here.
