Can virtual reality help in the treatment of ADHD?

Virtual-reality (VR) can be defined as an interactive computer-generated experience that can be similar to the real world or fantastical1. For instance, in a VR environment, a person is able to virtually live in the artificial world by looking and moving around it, as well as interacting with virtual characters or items2. Nowadays there are different kinds of VR environments, mainly used for entertainment purposes (e.g. video-games) or professional training (e.g. aviation, military training etc.)3. VR tools usually  range from a headset  (head-mounted displays with a small screens in front of the eyes), to proper full-scale rooms with bigger screens and special equipment  to increase the augmented reality experience.

Virtual reality head-mounted display. Image by Gerd Altmann from Pixabay.

VR has been recently investigated as a potential treatment for different metal health problems or psychiatric disorders such as social anxiety4, specific phobias5, post-traumatic stress disorder (PTSD)6, or persecutory delusions7. The key assumption behind the use of VR tools in mental health practice, relies in the fact that, in VR settings, individuals can repeatedly experience and learn appropriate coping strategies in a controlled environment8,9. For instance, knowing that the exposure is not real, allows people to face difficult situations and learn therapeutic strategies which they can then adopt in the real world?

..but how those VR tools can be used for the treatment of ADHD?

Recent evidence shows that VR can help enhance some of the core therapeutic challenges of ADHD such as attention, problem solving and managing impulsive behaviours10. For example, using VR can create virtual scenarios that can reward and empower skills such as response inhibition and emotional control10. One of the most commonly used scenarios is the class-room environment, which can introduce life-like distractions to asses children’s behaviour in an ecologically-based setting 10-11. In this virtual environment children with ADHD may be more able to use the trial-and-error instructional strategies to train learning skills11. For instance, in these VR settings, children with ADHD can also learn strategies to use in the real world without experiencing failures due to their experiences at school, making them more willing to accept the private feedback of the VR teacher.

Although VR ca be potentially used in ADHD treatment, is still an experimental procedure that needs more research to assess its validity. Also, there are still some concerns regarding potential side effects of long-term VR exposure, such as headaches, seizures, nausea, fatigue, drowsiness, disorientation, apathy, and dizziness10. Overall, despite its therapeutic potential, more studies are needed to assess its long-term treatment efficacy as well as the efficacy of VR environments compared to other non-pharmacological treatments already available for ADHD.

Isabella Vainieri and Jonna Kuntsi

Isabella Vainieri is a PhD student at the Social, Genetic & Developmental Psychiatry Centre at King’s College London.

Jonna Kuntsi is Professor of Developmental Disorders and Neuropsychiatry at King’s College London.

References

  1. Burdea, Grigore C. and Philippe Coiffet. Virtual Reality Technology. John Wiley & Sons, 2017.
  2. Rizzo AA, Buckwalter JG, Neumann U. Virtual reality and cognitive rehabilitation: a brief review of the future. J Head Trauma Rehabil. 1997;12:1–15.
  3. Johnson D. Virtual environments in army aviation training; Proceedings of the 8th Annual Training Technology Technical Group Meeting; Mountain View (CA), USA. 1994.
  4. . Maples-Keller JL, Bunnell BE, Kim SJ, Rothbaum BO. The Use of Virtual Reality Technology in the Treatment of Anxiety and Other Psychiatric Disorders. Harv Rev Psychiatry. 2017;25(3):103–113.
  5. Roy S, Kavitha R. Virtual Reality Treatments for Specific Phobias: A Review. Orient.J. Comp. Sci. and Technol;10(1).
  6. Rizzo A’, Shilling R. Clinical Virtual Reality tools to advance the prevention, assessment, and treatment of PTSD. Eur J Psychotraumatol. 2017;8(sup5):1414560. Published 2017 Jan 16. doi:10.1080/20008198.2017.1414560
  7. Freeman, D., Bradley, J., Antley, A., Bourke, E., DeWeever, N., Evans, N., Černis, E., Sheaves, B., Waite, F., Dunn, G., Slater, M., & Clark, D. (2016). Virtual reality in the treatment of persecutory delusions. British Journal of Psychiatry, 209, 62-67.
  8. Sanchez-Vives M, Slater M. From presence to consciousness through virtual reality. Nat Rev Neurosci 2005; 6: 332–9
  9. Slater M, Rovira A, Southern R, Swapp D, Zhang J, Campbell C, et al. Bystander responses to a violent incident in an immersive virtual environment. PLoS One 2013; 8: e52766.
  10. Bashiri A, Ghazisaeedi M, Shahmoradi L. The opportunities of virtual reality in the rehabilitation of children with attention deficit hyperactivity disorder: a literature review. Korean J Pediatr. 2017;60(11):337–343.
  11. Bioulac S, Lallemand S, Rizzo A, Philip P, Fabrigoule C, Bouvard MP. Impact of time on task on ADHD patient’s performances in a virtual classroom. Eur J Paediatr Neurol. 2012;16:514–521

The cortex and ADHD: the second project of the ENIGMA-ADHD collaboration.

After the first project on subcortical brain volumes in ADHD, published in Lancet Psychiatry in 2017 , ENIGMA-ADHD now analysed cortical data of 2246 people with a diagnosis of ADHD and 1713 people without, aged between four and 63 years old.  The data came from 37 research groups from around the world. FreeSurfer (imaging software) parcellations of thickness and surface area of 34 cortical regions were compared between cases and controls in 3 separate age groups; children, adolescents and adults.

ENIGMAADHD2JPG

Subtle differences only in the group of children were found. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found for thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.

These subtle differences in the brain’s cortex were not limited to people with the clinical diagnosis of ADHD: they were also present – in a less marked form – in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation-R study from Rotterdam, which has brain images on 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. In a third study, using the NeuroImage data from Nijmegen and Amsterdam, familial effects on those regions that showed case-control differences were investigated.  Siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.

We identified cortical differences that are consistently associated with ADHD combining data from many different research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and in unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioural and genetic studies.’ In the future, the ADHD Working Group, which is led by Martine Hoogman and Barbara Franke from the Radboudumc in Nijmegen, hopes to look at additional key features in the brain- such as the structural connections between brain areas – and to increase the representation of adults affected by ADHD, in whom limited research has been performed to date.

Link to the article: Hoogman et al., Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

To learn more about other projects that are carried out using ENIGMA-ADHD data, please also read the paper by Yanli Zhang-James and colleagues on bioRxiv. Here, the ENIGMA-ADHD data of the first and the second project were used to do prediction modelling.  

The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations. For more information about ENIGMA-ADHD please visit our website http://enigma.usc.edu/ongoing/enigma-adhd-working-group/ or contact Martine Hoogman martine.hoogman (at) radboudumc.nlenigma_300dpi

Epigenetic signature for attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is considered a complex disorder caused by underlying genetic and environmental risk factors. To make it even more complex, environmental factors can influence the expression of genes. This is called epigenetics.

Given the large proportion of the heritability of ADHD still to be explained, there is a growing interest in the epigenetic mechanisms that modulate gene expression. microRNAs (miRNA) are small parts in the human genome that do not code for genes, but instead regulate the expression of other genes by promoting the degradation or suppressing the translation of those target genes. miRNA therefore provide a means to integrate effects of genetic and environmental risk factors.

The human genome encodes more than 2500 different miRNAs, the majority of which are expressed in the brain. miRNAs are known to be involved in the development of the central nervous system and in many neurological processes including synaptic plasticity and synaptogenesis. Given the limited accessibility of the human brain for studying epigenetic modifications, miRNA profiling in peripheral blood cells is often used as a non-invasive proxy to study transcriptional and epigenetic biosignatures, and to identify potential clinical biomarkers for psychiatric disorders.

We recently investigated the role of microRNAs in ADHD at a molecular level, by conducting the first genome-wide integrative study of microRNA and gene expression profiles in blood of individuals with ADHD and healthy controls. We identified three miRNAs (miR-26b-5p, miR-185-5p and miR-191-5p) that have different expression levels in people with ADHD, compared to those without ADHD. When we investigated downstream miRNA-mediated mechanisms underlying the disorder this provided evidence that aberrant expression profile of these three miRNA may underlie changes in the expression of genes related with myo-inositol signaling. This mediates the biological response of a large number of hormones and neurotransmitters on target cells. We also found that these miRNAs specifically targeted genes involved in neurological disease and psychological disorders.

These findings show that epigenetic modifications through microRNAs play a role in ADHD, and provide novel insights into how these miRNA-mediated mechanisms contribute to the disorder. In the future, these miRNAs may be used as peripheral biomarkers that can be easily detected from blood, as is shown in the figure.

What´s next?

The mechanism through which miRNAs modify gene expression is complex and dynamic. Therefore, future studies are required to provide deeper insights into the epigenetic mechanisms underlying ADHD, and to identify specific molecular networks that may be crucial in the development of the disorder.

Further reading

Cristina Sánchez-Mora et al. Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells, Neuropsychopharmacology, volume 44, pages 890–897 (2019).

https://www.nature.com/articles/s41386-018-0297-0

About the author

Cristina Sánchez-Mora is postdoctoral researcher at the Psychiatry, Mental Health and Addictions group at Vall d’Hebron Institut de Recerca (VHIR). Her research is part of the CoCA consortium that investigates comorbid conditions of ADHD

German study first to show direct medical costs of ADHD and its comorbid conditions across the lifespan

Having ADHD is expensive. A study of German insurance data has shown that the medical costs of a person with ADHD are 1500 euro higher per year, compared to a person without ADHD. But that’s not all; individuals with ADHD are far more likely to suffer from additional conditions such as mood and anxiety problems, substance abuse or obesity. Treatment of these conditions can cost up to an additional 2800 euro per year. As ADHD – especially in adults – is still poorly recognised and diagnosed, these numbers may not reflect the complete picture of ADHD medical costs. Improving diagnosis and adult mental healthcare may prevent mental health problems later in life and actually reduce costs, argue Berit Libutzki and her co-authors.

ADHD (Attention Deficit / Hyperactivity Disorder) is a developmental condition. Symptoms arise before the age of 12 and are characterised by age-inappropriate and impairing behaviour in terms of problems with attention, impulsivity and hyperactivity. World-wide prevalence of children with ADHD is estimated around 5%, while in adults this is around 2.5%. This means that in about half of the children problems do not subside with age. For these people, ADHD is a lifelong condition that often impairs health, career and social life.

To estimate the economical costs of ADHD, Berit Libutzki and her colleagues from HGC Healthcare Consultants GmbH analysed the (anonymised) health insurance data of almost four million Germans. They compared the medical costs of people with an ADHD diagnosis to those of a well-matched group without ADHD.

medical costs per person_figure

The results showed that the medical costs of a person with ADHD are on average 1508 euro higher than those of a person without ADHD. These costs are mainly due to treatments in hospitals and by psychiatrists. ADHD medication itself (such as Methylphenidate) are in third place, contributing to only 11% of the additional costs. Other interesting findings from the study are that medical costs are a bit higher in women compared to men, and that costs are much higher in individuals over 30 years old compared to younger age groups. After the age of 18, the costs of for example ADHD medication drop, while psychiatrist costs and costs for other (non-ADHD) medications increase notably. Also sick payment is high in adult ADHD patients, leading to a significant increase in costs. One of the explanations for these cost increases could be a gap in care after leaving the regular care of a paediatrician at age 18, and the development of disorders that arise in addition to ADHD.

medical costs increase_figure

ADHD plus additional (mental) health problems

It has been shown before that having ADHD puts you at a much higher risk of developing additional (comorbid) disorders. Mood disorders – such as depression – and anxiety are most frequent; in the German data two-thirds of ADHD individuals over 30 had such an additional diagnosis (compared to only a fifth of adults without ADHD). Substance abuse and obesity are more common in people with ADHD as well. These comorbidities should not be underestimated as they add strongly to the burden of disease. The study shows that substance abuse and morbid obesity are even the most costly, especially in adulthood. In total, the surplus costs associated with these conditions are 1420-2715 euro higher for ADHD individuals, compared to individuals who suffer from mood or anxiety disorder, substance abuse, or obesity alone.

comorbid disorders_figure

Scientists think that certain genetic factors that play a role in ADHD also make a person more vulnerable for these comorbid health conditions. Libutzki and her team are part of the European research consortium Comorbid Conditions of ADHD (CoCA) that investigates the shared biological mechanisms of ADHD and these additional disorders. “Through this research we hope to find leads to prevent these disorders from developing, and improve mental health care.”, says the leader of the CoCA consortium Prof. Dr. Andreas Reif of the University Hospital Frankfurt.

“It is intriguing to speculate that these comorbidities, which were shown to be the important cost drivers in adulthood, could be prevented if mental healthcare were provided more constantly over the lifespan” write the authors. “The prevention of the development of comorbidities with age should be the focus of mental health care. Early treatment starting in childhood and continued treatment of adolescents into adulthood seem therefore advisable.”

Improving diagnosis and adult mental health care

There is one caveat in the study by Libutzki, that is also acknowledged by the authors: many people, especially adults, are not diagnosed with ADHD, even though they experience the symptoms. “Our knowledge gap is especially large in adulthood”, says Dr. Catharina Hartman from the University Medical Centre Groningen, The Netherlands. “The prevalence of adult ADHD in the health insurance data was very low (0.2 %). Given that the population prevalence for adult ADHD is 2,5 %, this indicates that many adults with ADHD are currently not diagnosed or treated. They may nonetheless make high direct costs since their ADHD may not be recognised, or they make indirect costs through unemployment or criminality.” This would indicate that the costs reported by the study are underestimated. On the other hand, adults often find out about their ADHD only after consulting a psychiatrist for other mental health problems. This would indicate that estimated costs and prevalence of comorbid disorders with ADHD in adulthood are overestimated, compared to when you were to include also all undiagnosed people with ADHD, and diagnosed persons who do not make costs (i.e. milder cases of ADHD).

The study thus provides a partial view on the costs of ADHD during the lifespan. That said, it is among the first to show in detail the lifespan medical costs of ADHD and comorbid disorders in Germany. These findings are likely to be representative of other western-European countries. Policy makers in these countries are strongly advised to investigate ways to improve the transition from child to adult mental healthcare and increase awareness about adult ADHD. This will not only improve the quality of life of many adults but may also save money.

Further reading

Libutzki, Ludwig, May, Jacobsen, Reif and Hartman (2019). Direct medical costs of ADHD and its comorbid conditions on basis of claims data analysis.  European Psychiatry, 58: 38-44. https://www.europsy-journal.com/article/S0924-9338(19)30019-7/abstract

The findings from this study are also summarised in an infographic: https://my.visme.co/projects/1jok0qg8-medical-costs-adhd

PROUD study interview with participants, part 3: Managing ADHD with light

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This month we interviewed a 22 year old female college student who took part in the CoCA-PROUD study in Frankfurt. I would like to thank her for sharing her valuable experience as a participant in our study and what is it like to live with ADHD.

What is it like to live with ADHD?

I’m usually very chaotic and it’s difficult for me to keep organized and remember appointments. I get distracted quickly and it’s hard to concentrate. My fellow students and friends find it sometimes annoying. I had difficulty with concentration and organization even in elementary school and not much has changed since then. But today I do have conscious strategies to organize myself a bit better. That helps in some situations.

I was only diagnosed with ADS 1.5 years ago at the age of 20. I was examined in elementary school because of similar problems and my parents decided me to take part in a psychological therapy but a diagnosis wasn’t given. On the one hand it was a relief when I got diagnosed, because I always thought I have problems in these things. But on the other hand, it also feels strange to have a diagnosis. Nobody really knows about it except my parents, my boy-friend and some best friends. I find it uncomfortable to talk about and I don’t want everyone to know that I have problems in these things, because so many people have prejudices.

For 1.5 years I’ve been taking medicine regularly. In some situations, I can tell that it helps, like to be able to concentrate better. In other situations, the effect isn’t as clear. But my boy-friend notices immediately if I haven’t taken my medication.

For me the positive side of ADS is that I often have more ideas than other people do and I also react more emotionally, for example when I’m happy. But still, on the medication, however, I also notice that most of the time I’m not as emotional as I normally would be.

Light therapy to manage ADHD

I saw the flyer that was posted on the homepage of the Department of Child and Adolescent Psychiatry at the Goethe University Hospital Frankfurt. I was searching online about research on ADHD because I was interested in research on ADHD in general and I wanted to learn more about the types of interventions investigated in the clinical study. Actually, I was most interested in the light therapy. I had read about it before and wanted to give it a try. So naturally I was excited when they told me that I was assigned to the light therapy group. I did the light therapy for 10 weeks starting in June 2018. They gave me a specific lamp and a smartphone with an app. I also had to wear the light sensor day and night, but it didn’t bother me. At work I wasn’t allowed to wear the sensor. The lamp was easy to use, however the light therapy needed to be done very early in the morning before I went to work. During the week, it was sometimes hard to find the time to do the light therapy early in the morning before heading to work. It was really hard to get up that early on Saturdays for it. That’s something that I didn’t like about the therapy. The app was easy to use. The feedback didn’t always work right, but that wasn’t important for me. During the 10 weeks of light therapy I felt much better in the mornings; it was easier to start the day and to get into the day. So in that way it was very helpful for me. I did not recognize any effects on my difficulties to concentrate or being organized. I would definitely recommend to participate in this study and to use the light. I am planning to buy one and to do light therapy on my own.

The interview was done by Jutta Mayer. She is a psychologist and psychotherapist at the University Hospital Frankfurt and the clinical project manager of the PROUD study which is part of the CoCA project (www.coca-project.eu).

 

MindChamp: Mindfulness for Children with ADHD and Mindful Parenting

Mindfulness for children with ADHD and their parents. Is that an alternative to medicine? Misha Beliën talks to Corina Greven about this question. She is project leader of MindChamp, an innovative study into the effectiveness of mindfulness as an addition to care-as-usual for ADHD.

Video originally posted on: http://www.bodhitv.nl

Researchers have found the first risk genes for ADHD

Our genes are very important for the development of mental disorders – including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results.   In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component.   Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH.  We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish iPSYCH group, which had access to many samples.

The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it – finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant.  The results of the study have just been published in the scientific journal Nature Genetics, https://www.nature.com/articles/s41588-018-0269-7.

These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some of the genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.

We study used genomewide association study (GWAS) methodology because it allowed us to discover genetic loci anywhere on the genome.  The method assays DNA variants throughout the genome and determines which variants are more common among ADHD vs. control participants.  It also allowed for the discovery of loci having very small effects.  That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.

The main findings are:

  1. A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD. None of these loci were traditional ‘candidate genes’ for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications. Instead, these genes seem to be involved in the development of brain circuits.
  2. B) we found a significant polygenic etiology in our data, which means that there must be many loci (perhaps thousands) having variants that increase risk for ADHD. We will need to collect a much larger sample to find out which specific loci are involved;

We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population.  This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population.  These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants

The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions:  Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders.   These analyses found a strong negative genetic correlation between ADHD and education. This tell us that many of the genetic variants which increase the risk for ADHD also make it more likely that persons will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population.

This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD.  When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.

Stephen Faraone is distinguished Professor of Psychiatry and of Neuroscience and Physiology at SUNY Upstate Medical University and is working on the H2020-funded project CoCA.