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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
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Nina (27 years, Dutch) participated in the PROUD-study and followed our light therapy. In this interview she describes the influences light therapy had on her ADHD symptoms.

What is it like to live with ADHD?

Please describe your main symptoms.

The symptom I experience as the most troublesome is making new friends. It is harder for me to make new friends, knowing I have fewer emotional and cognitive skills than peers. I am more sensitive to persons and situations and I experience them as more severe.

Besides, it is harder for me to see things in perspective and my perspectives change a lot over short periods of time. This makes it harder to look further in the future when making decisions. I also have less patience and it is harder for me to concentrate on a task. 

How does ADHD influence your life?

As I explained in the question before it can be tough to make friends. Concerning work, my ADHD has positive and negative effects. The negative effects are my lack of concentration, sometimes a job has to be done at a certain moment when I have no concentration, which can be a real struggle. The positive side is that I am creative and my spatial development is good. These are qualities that come handy at my job. Also my intelligence helps me. Because I am smart I can work fast at the moments my concentration is good, in order to compensate for the moments where my concentration is lost.

Do you think ADHD has any positive influences in your life?

It sure has, but these influences often last for a short period of time. I can be really enthusiastic and I am good at identifying people. This quality makes me a really good friend. Also my creativity is a positive effect of ADHD.

How have you been treated (medication/ psychotherapy)? What are the effects?

For a year and a half I have lived internally in a group especially for adolescents with ADHD and/or autism. Here I followed a training to improve my social abilities, how to engage in relationships with others and to be more independent.

From my 16th I take medication. I have switched a lot and tried different kinds of medication. Much of them did not work well for me, I even tried anti-depressants which made me feel sad. I am currently taking Stratera (short acting) and this works well for me. I don’t take it regularly but only at moments where I think I need it.

Study and intervention

How did you learn about the study?

I am regularly searching the internet to learn more about ADHD. This time I was searching information about comorbidity and neurodiversity and this is how I found your website, by chance.

What motivated you to participate?

It is a good thing that more research is done and I find it important to contribute. The more research is being conducted, the better others with ADHD can be helped. It is of great importance of me to be able to be a part in this. As long as we do not contribute to this kind of research, nothing will chance.

What were your expectations about the study before you started?

To be honest I did not have any expectations because I did not want to be affected by them.

What intervention did you participate in? When?

I participated in the bright light therapy from the 18th of October (2018) until the 10th of January (2019).

What did you like about the intervention? What did you dislike about the intervention?

At the beginning it was kind of hard, I found it really hard to be sitting still half an hour in the morning. Normally I rush through the mornings and do not really sit still at all. My solution was to put the lamp at my nightstand and sit in bed for half an hour in the morning, waking up next to the lamp. You can adjust the brightness of the lamp so I started with dimmed light and increased brightness step by step. Important is to sit upright because otherwise there is a chance of falling back to sleep!

In the beginning I had not realized what an impact this therapy has on your daily life, you really need the motivation to sit through, every day. After some time I got adapted to a new rhythm which made it easier to follow the light therapy for 6 times week. Only on Saturdays I skipped the sessions because of the weekend.

Was the intervention helpful?

It definitely has positive influences. The biggest change I have experienced is the adaptation to a more natural day/night rhythm. I was hoping a side effect would be falling asleep faster but unfortunately this was not the case for me.

The first days I experienced some negative side effects, which are explained in the bright light manual. Maybe it would be better if I had not read the manual because I was so focused on the experience of these side effects. What I felt was a really grumpy mood in the mornings. Luckily it only lasted for a few days.

Are you planning on continuing the intervention?

No, I have no plans of buying a lamp myself. Looking back at the intervention I think I would benefit more by participating in the aerobic exercise intervention, because sitting still for half an hour without a clear purpose is tough. Of course I did adapt to a better and more natural day/night rhythm because of the bright light therapy, but I think this could also be accomplished by going to bed at the same time every day.

Was it difficult/easy to use the App?

Definitely not difficult. The researches informed me about the sensor and how it might be inconvenient in the beginning but I only had to get used to it during the nights. The app was really clear and straight-forward, easy to use. I did forget the phone a few times, making me drive back home, but if you wear pants with pockets this should not be a problem.

Would you recommend other people with ADHD to participate in the study? Why?

I would definitely recommend it to people who are interested in this study and are motivated to participate. You really have to do it because you want it, not only because you want to help others.

Any suggestions/ways that the researchers could improve the experience for people in this study?

In my experience the study is set up well. Sometimes something went wrong (system was not installed right so they had to send me a new set, this set came without a wristband, red.) but the researchers handled it well and professionally. The researchers were cooperative and I liked participating in this study.

Lisa Bos, MSC works at Karakter Child and Youth Psychiatry and Radboud UMC (Nijmegen, the Netherlands) where she works as a researcher for the TRACE project and the PROUD-study. Both studies focus on additional treatments for ADHD and a healthy lifestyle which are also her main interests. She finds importance in studying socially relevant topics and improving the quality of care for ADHD patients.

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Have you ever thought that ADHD and autism could perhaps be the same disorder? – Or have you thought that they are way too different, two different planets in the psychiatric universe? Researchers do not agree on this. We know that both ADHD and autism are neurodevelopmental conditions with onset in childhood and that they share some common genetic factors, however, they appear with quite different phenotypical characteristics. We also know that people with ADHD or autism have an increased risk of getting other psychiatric disorders, so-called comorbidities, and smaller studies have shown that individuals with ADHD or autism get different psychiatric disorders, and at a different degree.

How can we utilize this knowledge about different psychiatric comorbidities between ADHD and autism? How can we get closer to an answer to this question; are ADHD and autism similar or different conditions? By using large datasets; unique population-based registries in Norway, we wanted to compare the pattern of psychiatric comorbidities in adults diagnosed with ADHD, autism or both disorders. In addition, we wanted to compare the pattern of genetic correlations between ADHD and autism for the same psychiatric traits, and for this, we exploited summary statistics from relevant genome-wide association studies.

In the registries, we identified 39,000 adults with ADHD, 7,500 adults with autism and 1,500 with both ADHD and autism. We compared these three groups with the remaining population of 1.6 million Norwegian adult inhabitants without either ADHD or autism. The psychiatric disorders we studied were anxiety, bipolar, depression, personality disorder, schizophrenia spectrum (schizophrenia) and substance use disorders (SUD).

Interestingly, we found different patterns of psychiatric comorbidities between ADHD and autism, overall and when stratified by sex (Fig.1). These patterns were also reflected in the genetic correlations, however, only two of the six traits showed a significant difference between ADHD and autism (Fig.2).

Figure 1. Prevalence ratios of psychiatric disorders in adults with ADHD, autism or both ADHD and autism, relative to the remaining population, by sex

Figure 1. Prevalence ratios of psychiatric disorders in adults with ADHD, autism or both ADHD and autism, relative to the remaining population, by sex. As can be seen in the figure, schizophrenia is more frequent in autism or ADHD+autism than ADHD alone, while the reverse is true for substance use disorder. There are also significant differences in prevalence between men and women. Figure from Solberg et al. 2019, CC-BY-NC-ND. Figure 2. A) The pattern of prevalence ratios of psychiatric comorbidity in adults with ADHD or autism observed in this study (ADHD; n=38,636, autism; n=7,528) and B) genetic correlations (rg) calculated from genome wide association studies

Figure 2. Left: The pattern of prevalence ratios of psychiatric comorbidity in adults with ADHD or autism observed in this study (ADHD; n=38,636, autism; n=7,528). Right: genetic correlations (rg) calculated from genome wide association studies. Psychiatric conditions are highly prevalent in both ADHD and ASD, with schizophrenia being most prevalent in ASD and antisocial personality disorders in ADHD. Genetic correlations are also high with both disorders, with especially high correlations between ADHD and alcohol dependence, smoking behavior and anti-social behavoiur. Major depressive disorder has high genetic correlations with both ADHD and autism. Figure from Solberg et al. 2019, CC-BY-NC-ND.

The most marked differences were found for schizophrenia and SUD. Schizophrenia was more common in adults with autism, and SUD more common in adults with ADHD. Associations with anxiety, bipolar and personality disorders were strongest in adults with both ADHD and autism, indicating that this group of adults suffers from more severe impairments than those with ADHD or autism only. The sex differences in risk of psychiatric comorbidities were also different among adults with ADHD and ASD.

In conclusion, our study provides robust and representative estimates of differences in psychiatric comorbidities between adults diagnosed with ADHD, autism or both ADHD and autism. With the results from analyses of genetic correlations, this finding contributes to our understanding of these disorders as being distinct neurodevelopmental disorders with partly shared common genetic factors.

Clinicians should be aware of the overall high level of comorbidity in adults with ADHD, autism or both ADHD and autism, and the distinct patterns of psychiatric comorbidities to detect these conditions and offer early treatment. It is also important to take into account the observed sex differences. The distinct comorbidity patterns may further provide information to etiologic research on biological mechanisms underlying the pathophysiology of these neurodevelopmental disorders.

This study was done at Stiftelsen Kristian Gerhard Jebsen Centre for Neuropsychiatric disorders, University of Bergen, Norway, and published OnlineOpen in Biological Psychiatry, April 2019, with the title:

“Patterns of psychiatric comorbidity and genetic correlations provide new insights into differences between attention-deficit/hyperactivity disorder and autism spectrum disorder”. https://doi.org/10.1016/j.biopsych.2019.04.021

Figure 1 and 2 are re-printed by permission https://creativecommons.org/licenses/by-nc-nd/4.0/

Berit Skretting Solberg is a PhD-candidate at the Department of Biomedicine/Department of Global Health and Primary Care, University of Bergen, Norway. She is also a child- and adolescent psychiatrist/adult psychiatrist. She is affiliated with the CoCa-project, studying psychiatric comorbidities in adults with ADHD or autism, using unique population-based registries in Norway.

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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.

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.nl

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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

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Mind the Gap Blog by María Soler Artigas - 1M ago

It is not uncommon for individuals to suffer from two or more psychiatric disorders at the same time. The appearance of these disorders frequently follows a specific order, and one disorder may predispose to others, all of which in combination contribute to the worsening of the quality of life of the individuals who suffer them. This is usually associated with more severe symptoms and worse prognosis. In addition, making a diagnosis and applying personalized treatments becomes more challenging in this context. By investigating the genetic overlap between disorders, we gain better understanding of why the disorders frequently co-occur.

In mental health, substance use disorders often appear when there is another mental condition. This is the case for attention-deficit/hyperactivity disorder (ADHD) and substance use disorder, where individuals with ADHD are more likely to use drugs during their lifetime than individuals who do not have ADHD. In particular, cannabis is the most commonly used substance among individuals with ADHD, which can also lead to the use of other drugs and to the worsening of their symptoms. ADHD is one of the most common neurodevelopmental disorders, affecting around 5% of children and 2.5% of adults, and is characterized by attention deficit, hyperactivity and impulsivity. Both ADHD and cannabis use are conditions determined partly by environmental factors but where genetic factors also play an important role.

We recently investigated the genetic overlap between ADHD and cannabis use, and found that the increased probability of using cannabis in individuals with ADHD, can be, in part, due to a common genetic background between the two conditions. We identified four genetic regions involved in increasing the risk of both ADHD and cannabis use, which could point to potential druggable targets and help to develop new treatments. In addition, we confirmed a causal link between ADHD and cannabis use, and estimated that individuals with ADHD are almost 8 times more likely to consume cannabis than those who do not have ADHD. This evidence goes in line with a temporal relationship, where the ADHD appears in childhood and the use of cannabis during adolescent or adulthood. This suggests that having ADHD increases the risk of using cannabis, and not vice versa.

This research has only been possible thanks to large international collaborations by the Psychiatric Genomics Consortium (PGC), iPSYCH, and the International Cannabis Consortium (ICC), where the genomes of around 85 000 individuals were analysed.

Overall, these results support the idea that psychiatric disorders are not independent, but have a common genetic background, and share biological pathways, which put some individuals at higher risk than others. This will help to overcome the stigma of addiction and mental disorders. In addition, the potential of using genetic information to identify individuals at higher risk will have a strong impact on prevention, early detection and treatment.

Further reading

María Soler Artigas et al. Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality, Molecular Psychiatry (2019) – https://www.nature.com/articles/s41380-018-0339-3

About the author

María Soler Artigas is postdoctoral researcher at the Psychiatry, Mental Health and Addictions group at Vall d’Hebron Institut de Recerca (VHIR), also part of the Biomedical Research Networking Center in Mental Health (CIBERSAM). Her research is part of the CoCA consortium that investigates comorbid conditions of ADHD.

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From road rage and bar fights to terror attacks and global confrontations, humans tend to be an aggressive species. On the average, members of the same species cause only 0.3 percent of deaths among mammals [1]. Astoundingly, in Homo sapiens the rate is around 2% (1 in 50), nearly 7 times higher! There are two crucial aspects that favor this kind of behavior: dwelling in social groups and being ferociously territorial. The chances are that struggle for various resources like suitable habitat, mates and food played a key role in shaping aggression in humans, favoring genetic variants that promote aggression and therefore increase changes of survival. Indeed, anthropologists who lived with exceptionally violent hunter-gatherers found that men who committed acts of homicide had more children, as they were more likely to survive and have more offspring [2]. This lethal legacy may be the reason we are here today.

You probably know some people that could be characterized as “having a short fuse”. Perhaps you have even pondered why they seem to have such a hard time to keep their temper in check? Indeed – while scientists have known for decades that aggression is hereditary, there is another crucial component to those angry flare-ups: self-control. In humans, the impulses to react violently stem from the ancient structures located deep within the brain. The part capable of controlling those impulses is evolutionally much younger and located just behind the forehead – the frontal lobes. Unfortunately, this “top-down” conscious control of aggressive impulses is slower to act compared to the circuits of eruptive violence deep in the brain.

People who are genetically predisposed toward aggression actually usually behave more violently than the average only when provoked. People not genetically susceptible to violent outbursts seem to be better able to remain calm and “brush it off”. The ones who are predisposed in fact try hard to control their anger, but have inefficient functioning in brain regions that control emotions – in the frontal lobes [2]. Several studies have found that men genetically susceptible to act aggressively are especially likely to engage in violence and other antisocial behavior if they were exposed to childhood abuse [3]. Again, we see that although genes may carry certain predispositions, there are essential environmental aspects that determine the final outcome.

Early physical aggression needs to be dealt with care. Long-term studies of physical aggression clearly indicate that most children, adolescent and even adults eventually learn to use alternatives to physical aggression [4]. Still, the importance of proper guidance and favorable environment cannot be understated. As mentioned before, Homo sapiens have been found to cause 2 percent of deaths among their fellows. However, this has fluctuated substantially throughout the history and in different cultures. During the medieval period, human-on-human violence was responsible for stunning 12 percent of recorded deaths. For the last century, people have been relatively peaceable compared to the Middle Ages, violence being the cause of death in just 1.33 percent of fatalities worldwide. In the least violent parts of the world today, the homicide rates are as low as 0.01 percent [1].

Our brains have evolved to monitor for danger and spark aggression in response to any perceived hazard as a defense mechanism. Aggression is part of the normal behavioral repertoire of most, if not all, species; however, when expressed in humans in the wrong context, aggression leads to social maladjustment and crime [5]. By identifying genes and brain mechanisms that predispose people to the risk of being violent – even if the risk is small – we may eventually be able to tailor prevention programs to those who need them most.

References

[1] Gómez, J. M., Verdú, M., González-Megías, A., Méndez, M. (2016). The phylogenetic roots of human lethal violence. Nature 538(7624), 233–237.

[2] Denson, T. F., Dobson-Stone, C., Ronay, R., von Hippel, W., Schira, M. M. (2014). A functional polymorphism of the MAOA gene is associated with neural responses to induced anger control. J Cogn Neurosci 26(7), 1418–1427.

[3] Cicchetti, D., Rogosch, F. A., Thibodeau, E. L. (2014). The effects of child maltreatment on early signs of antisocial behavior: Genetic moderation by Tryptophan Hydroxylase, Serotonin Transporter, and Monoamine Oxidase-A-Genes. Dev Psychopathol 24(3), 907–928.

[4] Lacourse, E., Boivin, M., Brendgen, M., Petitclerc, A., Girard, A., Vitaro, F., Paquin, S., Ouellet-Morin, I., Dionne, G., Tremblay, R. E. (2014). A longitudinal twin study of physical aggression during early childhood: Evidence for a developmentally dynamic genome. Psychol Med 44(12):2617–2627.

[5] Asherson, P., Cormand, B. (2016). The genetics of aggression: Where are we now? Am J Med Genet B Neuropsychiatr Genet 171(5), 559–561.

About the author:

Mariliis Vaht, PhD

Research Fellow of Neuropsychopharmacology at Institute of Psychology, University of Tartu, Estonia. Area of research: genetic and environmental factors in longitudinal health study designs.

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Is there an ‘average ADHD brain’? Our research group (from the Radboudumc in Nijmegen) shows that the average patient with ADHD does not exist biologically. These findings were recently published in the journal. Psychological Medicine.

Most biological psychiatry research heavily relies on so-called case-control comparisons. In this approach a group of patients with for instance ADHD is compared against a group of healthy individuals on a number of biological variables. If significant group effects are observed those are related to for instance the diagnosis ADHD. This often results in statements such as individuals with ADHD show differences in certain brain structures. While our results are in line with those earlier detected group effects, we clearly show that a simple comparison of these effects disguises individual differences between patients with the same mental disorder.

Modelling individual brains

In order to show this, we developed a technique called ‘normative modelling’ which allows us to map the brain of each individual patient against typical development. In this way we can see that individual differences in brain structure across individuals with ADHD are far greater than previously anticipated. In future, we hope that this approach provides important insights and sound evidence for an individualized approach to mental healthcare for ADHD and other mental disorders.

Individual differences in ADHD

When we studied the brain scans of individual patients, the differences between those were substantial. Only a few identical abnormalities in the brain occurred in more than two percent of patients. Marquand: “The brains of individuals with ADHD deviate so much from the average that the average has little to say about what might be occurring in the brain of an individual.”

Personalized diagnosis of ADHD

The research shows that almost every patient with ADHD has her or his own biological profile. The current method of making a diagnosis of psychiatric disorders based on symptoms is therefore not sufficient, the authors say: “Variation between patients is reflected in the brain, but despite this enormous variation all these people get the same diagnosis. Thus, we cannot achieve a better understanding of the biology behind ADHD by studying the average patient. We need to understand for each individual what the causes of a disorder may be. Insights based on research at group level say little about the individual patient.”

Re-conceptualize mental disorders

The researchers want to make a fingerprint of individual brains on the basis of differences in relation to the healthy range. Wolfers: “Psychiatrists and psychologists know very well that each patient is an individual with her or his own tale, history and biology. Nevertheless, we use diagnostic models that largely ignore these differences. Here, we raise this issue by showing that the average patient has limited informative value and by including biological, symptomatic and demographic information into our models. In future we hope that this kinds of models will help us to re-conceptualize mental disorders such as ADHD.”

Further reading

Wolfers, T., Beckmann, C.F., Hoogman, M., Buitelaar, J.K., Franke, B., Marquand, A.F. (2019). Individual differences v. the average patient: mapping the heterogeneity in ADHD using normative models. Psychological Medicine, https://doi.org/10.1017/S0033291719000084 .

This blog was written by Thomas Wolfers and Andre Marquand from the Radboudumc and Donders Institute for Brain, Cognition and Behaviour in Nijmegen, The Netherlands. On 15 March 2019 Thomas Wolfers will defend his doctoral thesis entitled ‘Towards precision medicine in psychiatry’ at the Radboud university in Nijmegen. You can find his thesis at http://www.thomaswolfers.com

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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.

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.

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.

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

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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).

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