The notorious evening chronotype and my master’s thesis

Almost every person, healthy or not, suffers from occasional problems with sleep and circadian rhythm. In the modern days of 24/7 smartphone use and transcontinental flights, our internal body clock is having a hard time adjusting to the external cues. For the persons suffering from mental health issues, their impaired sleep cycle can be one of the cornerstone problems of daily living. Sleep problems have been confirmed to be a first symptom, consequence, or even a cause of such psychiatric conditions as major depression, bipolar disorder, ADHD, autism, substance abuse, and even aggressive behaviour. Their strong relations, however, have not been studied systematically and broadly just yet.

Why study the circadian rhythm?

Circadian rhythm is our inner clock that regulates a lot of important processes in the human body, including the sleep/wake cycle, the release of hormones and even the way we process medicines. This clock is run by the brain region called the hypothalamus, which piles up a protein called CLK (referring to “clock”), during the daytime. CLK, in turn, activates the genes which make us stay awake, but also gradually increases the creation of another protein called PER. When we have a lot PER, it turns off CLK production and makes us ready to sleep. As CLK is getting lower, this causes a decrease in PER, so that the process starts again with elevating CLK waking us up. This cycle happens at around 24-hour intervals and is greatly influenced by so-called zeitgebers, or time-givers, like light, food, noise and temperature. When our retina neurons catch light waves, the suprachiasmatic nucleus in our brain stops the production of the hormone called melatonin that induces sleep and starts producing noradrenaline and vasopressin instead to wake us. This is the exact reason why you cannot fall asleep after watching a movie at night.

PER
Figure 1. The smart protein CLK wakes us up and its friend PER gets us to sleep.

Sometimes our body clock fails to function, as in the case of jetlag when we feel bad after changing a time zone or social jetlag when we have to start work early at 8 am. It can go as far as a circadian rhythm disorder meaning you have either a delay or advancement of sleep phases or an irregular or even non-24-hour daily activities preference. However, in the general population, a small variation in the rhythm is quite normal and is usually referred to as a chronotype. It defines your preference of when to go to sleep and do your daily activities and is divided into 3 distinct versions. The radical points of these variations include a morning chronotype, or “larks”, who go somewhat 2-3 hours ahead of the balanced rhythm, and an evening chronotype, or “owls”, who are a little delayed. The larks feel and function better during the first half of the day and go to bed rather early, while the owls prefer to work in the evenings and go to bed and wake up naturally late. The third chronotype is the in-between, balanced version of these two.

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Figure 2. The ‘owls’ seem to have questionable personalities and suffer from psychiatric conditions more often!

What’s my study about?

Previous research has shown that many psychopathologies are linked to an evening circadian preference. For my master thesis research, I am investigating whether we can identify specific profiles in sleep and circadian rhythm problems that are linked to specific mental health problems. There was even a curious study where researchers linked the Dark Triad personalities, which include people with tendencies for manipulation, lack of empathy, and narcissism, to the evening chronotype. Maybe this leaves some evidence for the famous quote that “evil does not rest”. However, there’s a great variation in sleep duration and perceived quality of sleep in patients with various diseases. We hope to divide such persons into more or less accurate groups with a sleep profile that would predict and aid the correct diagnosis of one or the other mental health condition.

The psychopathologies are included in our study as so-called dimensions, which look at each psychiatric syndrome not as with a norm/pathology cut-off but rather as a continuum of symptoms severity. This approach allows us to see if the sleep/circadian profile we identify refers to mental health in general or can be a distinguished part of a certain psychiatric condition. It might be that all dimensions, like depression and autistic spectrum disorders, have an evening chronotype and some non-specific sleep problems. Alternatively, we might find out that a person with symptoms of depression would sleep more or less than average and go to bed later, whereas a person with anxiety would go to sleep later as well but wake up at night very often despite an average summed up sleep duration.

The circadian rhythm changes throughout a lifetime from an early to an evening chronotype towards adolescence and then gradually shift back to the earlier preference with older age. Across the whole lifespan people constantly face varying quality of night sleep. Moreover, each psychiatric condition has a particular age of onset and sometimes changes its character with time. These are the reasons why our study will also look at how the sleep/circadian profiles change within the development phases from children (4-12 years) to adolescents (13-18) to adults (19-64) to the elderly (≥65) and if they affect males and females differently.

Why would it matter?

Should we discover distinct links between the profiles of sleep/circadian problems and certain conditions, other studies can then look into whether these profiles could be the reasons behind developing a mental health condition. It’d be interesting to finally learn what is a chicken and an egg in each profile-disease relation. For instance, should we really treat ADHD patients with melatonin and bright-light lamps instead of stimulants?

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Figure 3. Maybe if we adopt a typical cat’s lifestyle, we get less mental health problems. 🙂

Dina Sarsembayeva is a neurologist and a research master’s student at the University of Groningen. She is using the data from the CoCa project to learn if the chronotypes and sleep problems can be turned into profiles to predict specific psychiatric conditions.

Further reading

  1. Walker, W. H., Walton, J. C., DeVries, A. C. & Nelson, R. J. Circadian rhythm disruption and mental health. Transl. Psychiatry 10, (2020).
  2. Logan, R. W. & McClung, C. A. Rhythms of life: circadian disruption and brain disorders across the lifespan. Nature Reviews Neuroscience vol. 20 49–65 (2019).
  3. Jones, S. G. & Benca, R. M. Circadian disruption in psychiatric disorders. Sleep Med. Clin. 10, 481–493 (2015).
  4. Taylor, B. J. & Hasler, B. P. Chronotype and Mental Health: Recent Advances. Curr. Psychiatry Rep. 20, (2018).

Food & mental health: the Eat2beNICE project

We all know that a healthy lifestyle is beneficial for our health. But many of us forget that eating healthy, exercising regularly and getting enough sleep is also important for good mental health. In the Eat2beNICE research project a large team of researchers is investigating the link between food and mental health, specifically impulsivity, compulsivity and aggression. To share this knowledge with the rest of the world, they work together with food consultant Sebastian Lege.

The Eat2beNICE project just released a video to explain what the research is about and why it’s important. In this video Sebastian Lege visits the project coordinator Alejandro Arias-Vasquez, en several other researchers in the consortium.

More information about the Eat2beNICE project can be found at http://www.newbrainnutrition.com

 

 

 

 

 

How reliable is a diagnosis of ADHD in adults?

ADHD is classified as a neurodevelopmental disorder. This implies that ADHD starts during childhood and may, or may not, last into adulthood. According to this definition, a diagnosis of ADHD in adults requires two separate criteria to be satisfied: (i) Present diagnostic criteria must be fulfilled and (ii) ADHD symptoms must have started during childhood (before 7 years of age in DSM-IV and 12 years in DSM-5).

It’s relatively easy to evaluate present symptoms and differential diagnoses and to make a clinical decision. However, the second requirement has generated much headache and frustration. Is it really possible to evaluate childhood symptoms in a typical 40 year old patient, decades after the person left school and with limited documentation from family and peers?

Some argue that the criteria of childhood symptoms of ADHD are not satisfied unless there is a well-documented record of child developmental problems. Others put more faith in personal (subjective) recollection of childhood memories. These diverging views have culminated in an intense and heated debate about the possible existence of adult-onset ADHD and whether age-of-onset criteria are meaningful in clinical management of ADHD (1).

We all know from experience that memories tend to fade. Memories cannot be trusted. Research has shown that memories can be systematically biased and manipulated in many ways. Experimental psychology has provided a long list of well documented examples of memory bias, including mood congruent memory bias, consistency bias, positivity effect when older people favor positive over negative information in their memories, suggestibility bias when ideas suggested by the clinician are mistaken for true memories etc. (2). All of these effects and many more are well documented in forensic psychology and popular press and are experienced in routine clinical practise.

Despite of the obvious limitations of retrospective recollection of childhood experiences, a diagnosis of ADHD in adults is routinely based on retrospective reports of childhood experiences, often in the form of semi-structured interviews or rating scales. The Wender Utah Rating Scale (WURS) is the most widely used retrospective rating scale of childhood ADHD symptoms (3). The 25-item version of WURS has acceptable psychometrical properties, but its long-term stability is not known and it is also unclear how WURS scores are affected by other concurrent symptoms and conditions.

To investigate these factors, Lundervold and coworkers recently examined the test–retest reliability of the WURS in 85 adults with ADHD and 189 controls. They found that WURS scores were relatively stable over a time-span of seven years, but also that the scores were strongly influenced by present ADHD symptom severity, as well as other concurrent psychiatric disorders (4).

Based on these observations, the authors conclude that the WURS may be valuable in diagnostic assessments of ADHD, but that clinicians need to be cautious in the interpretation of the results. We all need to be aware of the many factors that can distort recollection of childhood memories. This study also demonstrates how difficult it is to strictly apply the age of onset criteria in adult psychiatric clinical settings.

References

  1. Franke B, Michelini G, Asherson P, Banaschewski T, Bilbow A, Buitelaar JK, Cormand B, Faraone SV, Ginsberg Y, Haavik J, Kuntsi J, Larsson H, Lesch KP, Ramos-Quiroga JA, Réthelyi JM, Ribases M, Reif A.Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan. Eur. Neuropsychopharmacol. 2018 Oct;28(10):1059-1088.
  2. Schacter DL, Dodson CS. Misattribution, false recognition and the sins of memory. Philos Trans R Soc Lond B Biol Sci. 2001 Sep 29;356(1413):1385-93.
  3. Stein MA, Sandoval R, Szumowski E, Roizen N, Reinecke MA, Blondis TA, et al. Psychometric characteristics of the Wender Utah Rating Scale (WURS): reliability and factor structure for men and women. Psychopharmacol Bull 1995;31:425–33.
  4. Lundervold AJ, Vartiainen H, Jensen D, Haavik J. Test-Retest Reliability of the 25-item version of Wender Utah Rating Scale. Impact of Current ADHD Severity on Retrospectively Assessed Childhood Symptoms. J Atten Disord. 2019 Oct 4:1087054719879501.

Mini-documentary: “Shine a light – understanding ADHD”

On the last day of the international ADHD Awareness Month, we are releasing a mini-documentary about ADHD. The hope is that this video will help young people and adults diagnosed with ADHD, or who suspect they have ADHD, as well as their family and friends, to understand the condition better.

“I feel like a universe, stuffed within a shoebox” – this is how Bryn Travers describes what it’s like to have Attention Deficit / Hyperactivity Disorder (ADHD). In this short film we have asked people with ADHD and their relatives about living with ADHD: what are the challenges and what are the things they like about ADHD? We have also asked clinicians and researchers working with ADHD to explain more about the origins of the disorder, what they have learnt from their experience working with patients, but also what are the main questions that research is trying to answer about ADHD.

Many children, adolescents and adults suffer from ADHD. ADHD is a complex disorder that affects people differently. Generally people experience problems in daily life, especially with respect to controlling attention, impulses and emotions. At the same time, people with ADHD enjoy their creativity and positive energy. Medication is effective for many people with ADHD, but not for all. That is why many people are interested in other types of (additional) treatment, such as meditation or diets. These types of treatment should therefore be better investigated. Knowing more about ADHD and spreading awareness will help people to understand what causes their behaviour. This will reduce stigma and (self)blame.

The video features four of the most well-known researchers in the field of ADHD: dr. Eric Taylor is emeritus professor of Child and Adolescent Psychiatry at King’s College London, dr. Philip Asherson is professor of Molecular Psychiatry at King’s College London, dr. Barbara Franke is professor of Molecular Psychiatry at Radboud university medical center Nijmegen (The Netherlands), and dr. Corina Greven is psychologist and behavioural geneticist at Radboud university medical center Nijmegen. Next to these scientists and psychiatrists, we see three people with ADHD (Bryn Travers, Evie Travers and Aziz), Andrea Bilbow, president of patient organisation ‘ADHD Europe’ and mother of two children with ADHD, and dr. Kai Syng Tan, researcher and artist at King’s College London, who also has an ADHD diagnosis.

This film was created through the MiND research consortium, in collaboration with the consortia Aggressotype, CoCA and Eat2beNICE. These consortia are all funded by the European Commission through the FP-7 and horizon2020 programs. Young researchers dr. Nicoletta Adamo and Laura Ghirardi are the brains behind this film, with the help of the MiND training program and 4QuarterFilms.

Do you want to help us spreading awareness about ADHD? Then share this video with everyone you know! The video also contains subtitles in English, Dutch, German, Spanish, Italian, Swedish and Hungarian (and more languages may follow).

You can watch the video here:

ADHD Awareness month: Interview with a Participant

This month is the ADHD awareness month and we wanted to share with you an interview with one of the PROUD participants (CoCA project, Comorbid Conditions of ADHD).

The participant is a 21-year old male college student who is originally from Peru but has been living in Barcelona for a few years. He participated and did the exercise intervention of the PROUD Study.

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  1. What is it like to live with ADHD?

Please describe your main symptoms. Have your symptoms changed since childhood vs. adulthood?

When I was an adolescent, my main symptoms were low concentration capacity and hyperactivity (I could not sit for a long time). I was always bored and doing too many things at the same time. I was very impulsive as well and I had problems with my family and friends because I meddled in their activities and conversations.

Now I am 21 years old and I notice I have less hyperactivity and I can control more my impulsivity. On the other hand, my concentration is still bad and I need external help in order to improve it (pharmacology).

When were you diagnosed with ADHD? By whom? How did you feel about getting the diagnosis?

When I was 11 years old, I had very many academic difficulties and the school Psychologist noticed some ADHD symptoms in me. So, she sent me to a specialized psychology center and I was diagnosed with ADHD. This was in Perú, my country, but here in Spain I repeated some tests and I was diagnosed again and the psychologist confirmed the diagnosis.

At that time, I felt like the most weird kid in my class because I had to spend  some hours with the School psychologist and do some separate activities from the other children. My classmates asked me all the time where I was going and this bothered me.

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

When I was in Perú, I remember my parents gave me a syrup (I don’t remember the name) and my teachers were worried because they said I didn’t move from my chair in all day long, like I was sedated. My parents worried as well, and stopped giving it to me.

Then when I was older, in Spain, my brother told me I was very disorganized and I didn’t use the time well (referring to my studies). So I went to a different doctor and I started with ADHD medication.

The main effects I notice are irritability, low mood, less spontaneity and the fact that I prefer to be alone because I have a lot of concentration.

How does ADHD influence your life? (Work, friends/partnership, hobbies etc.)

When I was kid it was more difficult because I wanted to be like the other kids and be treated like a “normal” kid at school. I am competitive and I wanted to achieve the same goals as the other kids.

Regarding the friendships, it depends because there are times I want to be with friends and there are times I prefer to be alone. Some friends have been angry with me because I didn’t pay attention to them for a long time.

Do your friends/ colleagues know about your illness?

I mentioned the ADHD to a few friends and classmates because they didn’t understand some things about my behavior, my mood changes, etc. Sometimes I think people think I am dumb or something when I explain to them about the ADHD. That’s because it is difficult to me to talk about my disease.

What is the worst thing about having ADHD?

The worst thing about having ADHD is that people have a lot of prejudices about it and have a lot of incorrect thoughts about what it means. Some people told me that I will become a drug addict because I was taking pills for ADHD, they always think I don’t need the pharmacology. People usually treat me like a lazy person but I am not lazy, I just have low concentration capacity.

Sometimes, I believe that I won’t be able to achieve my objectives, I feel like I am not good for anything, and this is the saddest part about ADHD for me.

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

I think so. I have had to be creative and follow my own strategies. I have been alone (without any friends) sometimes but this has made me stronger. And the most important thing, I know I have difficulties because of ADHD but I have learned to be a tenacious person and never give up.

  1. Study and Intervention

How did you learn about the study?

My psychiatrist from Vall d’Hebron told me about the study.

What motivated you to participate?

What motivated me the most is that if I participate in this kind of study, it could help the professionals to investigate and improve the ADHD treatments.

What were your expectations about the study before you started?

I wanted to learn more about this illness so I thought this study could help me too.

What intervention did you participate in? When?

I did the Exercise condition. I started 5 months ago more or less.

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

I really liked the fact that I had a continuous monitoring and regular visits. Furthermore, the psychologist J.P. helped me a lot to understand all the devices I had to use and was very patient with me. She also helped me with more ADHD issues and gave me good advice.

On the other hand, what I didn’t like was the sensor I had to wear all the time because it was very big and uncomfortable.

Was the intervention helpful? (Any effects on ADHD core symptoms, mood, sleep, weight, fitness etc.?)  

I think the intervention was helpful for improving my physical condition and I was more tired so it helped me to sleep better. I also understood that my emotions and mood are important and that I have to take care of my mental health.

Was it difficult/easy to use the App?

It was easy to use the App but sometimes I had doubts about the sensor, because I didn’t know if it was synchronized with the smartphone or not.

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

Yes, I would recommend it, because it is important to investigate and you can learn more about the symptoms and adverse events of ADHD.

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

I would just change the sensor or the fact that you have to wear it all the time. I was embarrassed and it was very big.

 

 

Are you interested in participating, or do you want more information?

The trial will be continued until 2020. All outpatients with ADHD aged 14 to 45 years old living in and around Barcelona, Frankfurt, London or Nijmegen are invited to participate in the trial.

Contact:

Barcelona: judit.palacio@vhir.org

Frankfurt: Proud-Studie@kgu.de

London: adam.1.pawley@kcl.ac.uk

Nijmegen: proud@karakter.com

More information about the trial can be found on the CoCA website: http://coca-project.eu/coca-phase-iia-trial/study/

10 weeks of physical exercise or light therapy: what’s it like to participate in our clinical trial?

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In 2017, under the umbrella of an EU-funded CoCA project (Comorbid Conditions of ADHD), we started a pilot clinical trial to test the potential of bright light therapy and physical exercise to improve and prevent depression and obesity in adolescents and young adults with ADHD. Our aim is to provide non-pharmacological interventions that could easily be done at home and integrated into daily routines.

The study (named PROUD) is simultaneously going on in Frankfurt, Barcelona, London and Nijmegen. 60 people have already participated across these different locations. As the study is still ongoing (we’re about half way), we don’t have the results yet. However, we have interviewed some people who have taken part so far about their experiences with the interventions and their experience of living with ADHD. Their enlightening reports also give us the great opportunity to learn more how it feels for adolescents and young adults to live with ADHD – a disorder that is still seen as predominantly childhood condition. These interviews will be posted on this blog in the following months, but the first one you can already read here. We would like to extend our gratitude to our study participants, not only for participating but also for giving up their time to answer our questions.

Awareness about ADHD

This month – which is the ADHD awareness month -, we interviewed a 21-year old male college student who is originally from Peru but has been living in Barcelona for a few years who participated in the exercise intervention. You can read the interview here. During this interview he said that “The worst thing about having ADHD is that people have a lot of prejudices about it and have a lot of incorrect thoughts about what it means.” These real-life patient highlighted issues emphasize the importance of raising public awareness of ADHD.

 About the clinical study

Stimulant medications are the mainstay treatment for the typical symptoms of ADHD1. However, many patients (about 85% of adults with ADHD)) also suffer from psychiatric and somatic comorbidities – including mood disorders2 and obesity3. The risk for these co-morbid conditions is especially high for patients during adolescence and young adulthood4. Bright light therapy (BLT) is an established therapy for major depression and exercise prevents and reduces obesity and improves depressive symptoms, however it is not yet known whether these therapies are effective in adolescents and adults with ADHD. To support patients during the 10 weeks of intervention, a mobile technology was developed specifically for this trial by the Karlsruhe Institute of Technology. Patients receive app-based instructions and feedback via a smartphone and they wear a sensor that records their physical activity and light exposure throughout the study. We earlier wrote about this study in two Blogs. CoCA-PROUD trial ready to roll How bright light and physical exercise might help ADHD patients

Are you interested in participating, or do you want more information?

The trial will be continued until 2020. All outpatients with ADHD aged 14 to 45 years old living in and around Barcelona, Frankfurt, London or Nijmegen are invited to participate in the trial.

Contact:

Barcelona: judit.palacio@vhir.org

Frankfurt: Proud-Studie@kgu.de

London: adam.1.pawley@kcl.ac.uk

Nijmegen: proud@karakter.com

More information about the trial can be found on the CoCA website: http://coca-project.eu/coca-phase-iia-trial/study/

References    

1Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727-738.

2Jacob CP, Romanos J, Dempfle A, Heine M, Windemuth-Kieselbach C, Kruse A, et al. Co-morbidity of adult attention-deficit/hyperactivity disorder with focus on personality traits and related disorders in a tertiary referral center. Eur Arch Psychiatry Clin Neurosci. 2007;257:309–17.

3 Cortese S, Moreira-Maia CR, St Fleur D, Morcillo-Penalver C, Rohde LA, Faraone SV. Association between ADHD and obesity: a systematic review and meta-analysis. Am J Psychiatry. 2016;173:34–43.

4Meinzer MC, Lewinsohn PM, Pettit JW, Seeley JR, Gau JM, Chronis-Tuscano A, et al. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood. Depress Anxiety. 2013;30:546–53.

This post was written by Jutta Mayer and Adam Pawley. Jutta Mayer is a psychologist and psychotherapist at the University Hospital Frankfurt. She is the clinical project manager of the PROUD study which is part of the CoCA project (www.coca-project.eu). Adam Pawley is a clinical neuroscientist at King’s College London. He is conducting the PROUD trial in London.

It’s ADHD awareness month!

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October is the international ADHD awareness month. This initiative of the European ADHD patient organisations aims to raise awareness about ADHD, and funding for more research to understand ADHD. Throughout Europe many events will be organised this month to inform people about ADHD. Because although most people have heard about ADHD, there are still a lot of misconceptions and misunderstandings of what ADHD really is.

This year’s theme of the ADHD awareness month is ADHD and employment. As ADHD is increasingly being recognised as persisting into adulthood, ADHD on the work floor is something to take into account as well. The bad news is that unemployment rates are higher for people with ADHD [1] as well as the number of absence days and turnover rates [2]. But the good news is that ADHD is often associated with entrepreneurship. For instance, a large registry-based study showed that a high number of hyperactive symptoms is related to a high chance of being self-employed [3].

According to Andrea Bilbow, president of the European organisation ADHD Europe, “it should be more widely known that people with ADHD have great skills to offer to employers. It is important for employers to understand that ADHD is a disability, and that people with ADHD can be a great asset if you find their strengths. Employers should be aware that if you help employees with ADHD to scaffold the things they’re less good at, then they can excel at the things they are good at. For instance, in general people with ADHD are very good in IT, in problem solving, and in fixing things. They are often less good at paper work and processing a lot of information. So one piece of advice is to not overload them with too many instructions. Instead, if you give them one task at a time and they will do task incredibly well.” So are you an ADHD-friendly employer? We previously posted a blog on this.

The ADHD researchers that are affiliated with the MiND the gap-blog are also contributing to ADHD awareness month. We will be posting several blogs this month about our ongoing studies and recent publications on ADHD and comorbid disorders (i.e. from the CoCA project). Furthermore, at several European sites researchers are organising events to raise awareness about ADHD. In Nijmegen, The Netherlands, for instance you can come to the university’s open day on October 6 and draw your own superhero with ADHD (you can even win a prize!). Also check out the website of the ADHD patient organisation in your country or city to find out more about what’s happening.

Last, but definitely not least, we will soon be releasing a short documentary about ADHD that was created through the MiND-project, in collaboration with the other EU-funded projects and research consotira (Aggressotype, CoCA and Eat2BeNICE, IMpACT). So keep following this blog for updates, and spread the word about ADHD awareness!

For more information about ADHD awareness month, visit the website of ADHD Europe: https://www.adhdeurope.eu/

 

Jeanette Mostert is dissemination manager for the projects CoCA and New Brain Nutrition (Eat2BeNice).

 Further reading

[1] Kuriyan, A.B., Pelham, W.E., Molina, B.S.G. et al. (2013) Young Adult Educational and Vocational Outcomes of Children Diagnosed with ADHD. J Abnorm Child Psychol, 41: 27-41. https://doi.org/10.1007/s10802-012-9658-z

[2] Kleinman, N.L., Durkin, M., Melkonian, A., Markosyan, K. (2009) Incremental Employee Health Benefit Costs, Absence Days, and Turnover Among Employees With ADHD and Among Employees With Children With ADHD. Journal of Occupational and Environmental Medicine, 51: 1247-1255 doi: 10.1097/JOM.0b013e3181bca68c

[3] Verheul, I., Rietdijk, W., Block, J. et al. (2016) The association between attention-deficit/hyperactivity (ADHD) symptoms and self-employment. Eur J Epidemiol, 31: 793. https://doi.org/10.1007/s10654-016-0159-1

A Meeting of MiNDs

On Friday 1st June the MiND EU project hosted a successful patient information evening in collaboration with ADHD-Europe, the ADANA Foundation and Dr Toni Ramos-Quiroga at Vall d’Hebron Hospital in Barcelona. Anyone with an interest in research into Autism and ADHD were warmly invited to view posters and presentations on the latest developments from the MiND project and our collaborators.

Patient evening blog 1

The world of science is often seen as having a mind of its own, which does not often engage with the community. However, the MiND project would like to change this perception! We hosted a patient information evening to discuss our work on ASD and ADHD with the public, with the aim to share our knowledge of these disorders and to promote inquisitive minds.

The presentations were opened by Dr. Toni Ramos-Quiroga and Andrea Bilbow OBE, President of ADHD Europe. Although our speakers varied in their backgrounds, they are all active in genetics and psychiatric research, with a passion to improve our understanding of ADHD and ASD.

Professor Bru Cormand, who leads a Neurogenetics Research Group at the University of Barcelona, talked about the genetics of Autism and ADHD and the role of the environment in the development of these disorders. Professor Cormand explained that we share more than 99% of our genome with any other human being, so it is the remaining 1% which makes the differences among individuals, both in health and disease. Biomedical researchers look into this fraction of the genome to find the causes of many diseases. These genes are instructions for producing proteins, some of which are involved in the communication process between neurons in our brain. It is important that we study these genes because the connectivity between neurons is crucial. When this mechanism is impaired, due to alterations in certain genes, the result is often a  psychiatric condition like ADHD or ASD.

Professor Cormand also explained how we can use family studies to understand ASD and ADHD. From this type of research we now know that genetic factors play a very important role both in ADHD and in ASD, with a share of more than 70%. The rest possibly corresponds to environmental risk factors, such as prenatal or birth complications. Other external factors, like vaccines, do not contribute to these disorders. To date, we have been able to identify several contributor genes for both ASD and ADHD. Professor Cormand eloquently described our genome as a ‘crystal ball’ “if correctly asked, it can provide information about things that will take place in the future. Our health and our disease is, to a great extent, written in the genes… but they can also help us to find ways for improvement”.

Further research in this area will be highly beneficial for patients in the future for several reasons:

  1. They provide basic knowledge on the causes of the disorders, which can be useful in diagnosis or even for prognosis (anticipation of future complications).
  2. It points at potential therapeutic targets, i.e. proteins that can be targeted with drugs.
  3. The genetic profile of an individual can predict response to a treatment or side effects, if any.

However, we still need some time to complete the full genetic landscape before we fully understand these disorders!

Dr Alejandro Arias-Vasquez, an associate professor in genetic epidemiology informed attendees of an exciting, up and coming area of research: the microbiome and its role in ADHD. Through research we have learned which are “good” and “bad” foods that influence the risk of being obese, having diabetes, or suffering from cardiovascular disease.  However, we are also beginning to learn that what people eat can also affect the way the brain works, although these mechanisms are currently unclear.

So far research has shown that there is convincing evidence of a sizeable impact – both harmful and protective – of nutrition components on behaviors such as impulsivity and compulsivity. Currently, the experts do not know how big the impact (effect size) of these non-pharmacological interventions is, which raises questions such as:

  • Can people improve our overall brain functioning by improving diet and lifestyle?
  • Can we replace medication used for treating psychiatric disease with specific diets?
  • Shall we complement pharmacological treatment with specific diets to improve behavior?

Dr Arias-Vasquez hopes to answer these questions by leading a new research consortium called Eat2beNICE. This project will study different diets and nutritional supplements in children and adults. It is anticipated that this research will create new evidence-based approaches for making recommendations about nutrition and its links to changing behavior. This could mean that specific dietary changes could be one or part of the treatment options for ASD and ADHD in the future.

Patient evening blog 2

Dr Laura Gisbert explained her research as a psychiatrist at Vall d’Hebron. Currently, Dr Gisbert is involved with many research projects (that take place in her clinic). In particular, there are two clinical trials testing out medications for ASD and ADHD: Vasopressin for adults with ASD and Guanfacine for children with ADHD. Dr Gisbert explained that two main approaches are used to develop pharmacological agents for ASD. One is re-purposing treatments from other psychiatric disorders that have symptoms in common with ASD. The second approach is to target the neurobiological processes underlying ASD. Although there have been studies of medications that reduce ASD symptoms, by targeting specific circuits in the brain, there is still a lack of clear evidence to recommend the routine use of any of these medications for the moment. Similarly in ADHD, more research is needed to find effective medications with fewer side effects. Not all patients can tolerate stimulant medications that are often prescribed for ADHD, and therefore alternatives need to be found. Furthermore, this medications that can simultaneously improve symptoms of frequently co-occuring disorders such as ASD, would also be advantageous to patients. It is hoped that the clinical trials taking place at Val d’Hebron will contribute to this work, in order to improve treatment strategies for patients with ASD and/or ADHD.

These presentations were highly engaging as demonstrated by our audiences need for a long Q&A session with our speakers on various topics from treatment strategies to genetics.

Patient evening blog 3

Attendees were also highly interested in the poster presentations given by the MiND early stage researchers (Viola Palladino, Niall Mortimer, Anu Shivalikanjli, Joanna Szopinska-Tokov, Sara Boxhoorn and Francesca Waddington). These posters represented the diverse range of topics studied within the MiND project, which include the gut microbiome in ADHD, the genetics of ADHD, stem cell research, how we measure attention in ASD and ADHD and the relationship between these two disorders. These also proved to be very thought-provoking with many discussions between members of the public and our researchers.

The MiND project is proud that our event was so insightful and to have elicited such a great response!

If you would like to find out more about our research see
mind-project.eu
Eat2beNice

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How sports might help in adult ADHD

A recent case in our outpatient clinic gave me an interesting insight into the link between professional sports and adult ADHD. An US-American football player who was quite impulsive presented for a diagnostic assessment. He had a history of childhood ADHD but never received stimulant treatment because his mother felt that she was able to cope by providing a structured environment. While he was not very successful in obtaining an economy degree during college, he earns nowadays money playing in foreign American football leagues. He is now 35 years old and started to think about what to do after his career ends and how his ADHD would affect future plans. He clearly fulfilled most diagnostic criteria but was not too handicapped in everyday life. Obviously, he found the perfect niche for a hyperactive adult with a high degree of impulsivity: American football. During the diagnostic assessment, he had to do a commercial continuous performance test which tests both attention as well as hyperactivity over 20 min. While his attention was not to bad, his activity during the tests was one of the highest scores we saw so far in our outpatient clinic. When talking to him about his test results, he commented that this result is typical for his adult life: professional sports taught him how to deal with his inattention and consecutive frustration. So while his ADHD was manifesting in lots of micro movements he nevertheless was able not to loose motivation and to sustain a certain degree of attention until the end of this test. So after having seen this patient, I wondered what evidence we have so far to recommend sports training in adult ADHD. Obviously, we might think of three good reasons for sports in general and in adult ADHD patients.

First, people showing a high degree of restlessness, will just enjoy sports and fitness training because it helps them to reduce their restlessness.

Second, the neurotransmitter dopamine plays a decisive role in mediating all effects in adult ADHD. There is this elegant rat experiment (by Kim et al. 2011) about the effect of a treadmill exercise on the dopamine system. Spontaneous hypertensive rats, a special breed which shows signs of hyperactivity and is considered to be an ADHD model, were given methylphenidate or treadmill exercise. While the improvement due to MPH is not surprising, treadmill exercise impacted on expression of BDNF, a marker for neuroplasticity, in the striatum and the substantia nigra.

Apart from these direct neurochemical effects, some sports training teaches how to handle frustrating challenges and not to give up early. While this is a trivial statement for every ambitious sportsmen, there are only few scientific or clinical studies in sports psychology which assessed this statement systematically and almost none for adult ADHD (please correct me if I’m wrong).

Inspired by my patient’s story, I became curious whether frustration handling could be a way of how adult ADHD patients might learn to cope with their disease. Maybe some readers have own thoughts about this?

Reference:

Kim, H., Heo, H. I., Kim, D. H., Ko, I. G., Lee, S. S., Kim, S. E., … Kim, C. J. (2011). Treadmill exercise and methylphenidate ameliorate symptoms of attention deficit/hyperactivity disorder through enhancing dopamine synthesis and brain-derived neurotrophic factor expression in spontaneous hypertensive rats. Neuroscience Letters. https://doi.org/10.1016/j.neulet.2011.08.052

Oliver Grimm is a senior psychiatrist at the University Hospital Frankfurt where he is responsible for the adult ADHD outpatient clinic and is involved in the CoCA-project ( www.coca-project.eu ).

Exciting findings on ADHD comorbidities shared on 3rd meeting of CoCA researchers in Dublin

A few weeks ago, researches from all over Europe (and some even from the USA) gathered in Dublin to discuss the progress of the CoCA project. This project, investigating the prevalence and causal factors of ADHD comorbidities, is now almost half way. Time for an update on what’s happening. 

CoCA Dublin
All attendees of CoCA’s 3rd general assembly meeting in Dublin

ADHD is a risk factor for developing other (psychiatric) disorders

One of CoCA’s aims is to estimate the prevalence of comorbid disorders that occur together with ADHD. By using very large data registries from Norway, Sweden, Denmark and Estonia we can estimate the risk of developing a psychiatric comorbidity when a person has ADHD. For instance, last month a paper was published based on data from Norway, stating that the prevalence of anxiety, depression, bipolar and personality disorders, schizophrenia and substance use disorders is 4 to 9 times higher in adults with ADHD compared to adults without ADHD [1]. Interesting differences between men and women were also observed in this study. Such that depression is much more prevalent in women with ADHD, compared to women without, while in men substance use disorders are more common together with ADHD.

ADHD does not only co-occur with other psychiatric disorders, but also with obesity. Earlier last year, we published a study based on the Swedish national registry, where it was observed that ADHD and being overweight or having obesity share familial risk factors [2]. In other words, when you have a sibling who is overweight or has obesity, you are more likely to have ADHD compared to similar people who do not have overweight siblings.

The data from these registries can not only be used to estimate prevalence, but also to predict the risk someone has to develop other disorders. Our partners in the USA are using advanced machine learning tools to predict within the ADHD population who will develop comorbid disorders. Using the Swedish registry data they have found that having an ADHD diagnosis combined with a high number of injuries before the age of 12 predicts a comorbid substance use disorder at a later age. High risk taking behavior could mediate this association, and may therefore be a trait to investigate further and monitor in young people with ADHD. These data are now being further investigated and have not yet been published.

Publications on other registries and data will come out soon, so keep your eye on this blog for more information on the co-occurrence of (psychiatric) disorders in persons with ADHD.

ADHD and (psychiatric) comorbidities share genetic variants

When you know that ADHD often co-occurs with other disorders, the next question is to understand how and why. Our geneticists are trying to map the genetic overlap between the different disorders and identify shared genetic risks. Much of the work is still ongoing, but you can expect some exciting findings to be published very soon. What I can already share is the recent publication on how polygenic risk scores of ADHD overlap with other disorders and traits [3]. Polygenic risk scores (PRS) were calculated based on 12 genetic loci that are associated with ADHD based on earlier studies. In other words, the more risk variants you have on these loci, the higher your risk is for ADHD. Using the UK Biobank data, the researchers found that ADHD PRS were associated with higher body mass index, neuroticism, anxiety, depression, alcohol and nicotine use, risk taking and lower general cognitive ability (verbal-numerical reasoning). This suggests that the genes that contribute to ADHD are also involved in other traits and disorders that are often observed in people with ADHD. More knowledge on these genetic factors is expected from the studies that are now being conducted.

Searching for new treatment possibilities for ADHD and comorbid disorders

At the moment, there are no good treatments for obesity and substance use disorders, and there is little progress in the development of medication for ADHD in combination with depression. Within the CoCA project we are therefore investigating new treatment possibilities. In Frankfurt, Barcelona and London the first people with ADHD have received bright light therapy and physical exercise training to reduce symptoms of depression (the PROUD study). In Nijmegen this study will soon start as well. Meanwhile in Rostock (Germany), the circadian rhythm of participants with ADHD and other disorders is being measured. And in Frankfurt researchers are investigating the effects of dopamine agonists and antagonists on the reward system in the brain.

CoCA researchers in Norway have been searching the literature for new druggable targets for ADHD and comorbid disorders. A publication on many promising druggable genes can be expected soon. The first group of targets will be tested in an animal models.

Collaborations with patient organisations

Two representatives of ADHD patient organisations also joined our meeting: Andrea Bilbow from ADHD Europe, who is a partner in the CoCA project, and Ken Kilbride from ADHD Ireland. It was good to have these experts with us, and discuss with them how we can best translate our research findings to the people who should benefit from these findings. In Ireland for instance, there is very little knowledge about adult ADHD amongst health care professionals. It is therefore essential that our knowledge is also transferred to them, so that they can provide better care.

With the help of Andrea and Ken, we came up with a lot of new ideas for ADHD Awareness Month. During the entire month of October we aim to generate more awareness about. We will specifically target schools, such as universities and German Berufschule to inform both pupils and teachers about how to recognise ADHD and comorbidities, in adolescence and adulthood.

What’s next?

With the project being almost half way, we feel that we’re progressing very well (and our external advisor Jim Swanson – who attend the meeting as well – agrees!). In the coming year, we expect many exciting publications to appear and we will organise several symposia on international scientific conferences to share with you what we’ve found. By collaborating with patient organisations across Europe we will also share our knowledge with patients, family members, health care professionals and teachers. You can follow all of our progress on this blog!

This blog was written by Jeanette Mostert. Jeanette is dissemination manager of the CoCA project.

Further reading

1: Solberg, Halmøy, Engeland, Igland, HAavik & Kungsøyr (2018) Gender differences in psychiatric comorbidity: a population‐based study of 40 000 adults with attention deficit hyperactivity disorder. Acat Psychiatria Scandinavia, 137 (3): 176 – 186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838558/

2: Chen, Kuja-Halkola, Sjölander, Serlachius, Cortese, Farone, Almgvist & Larsson (2017) Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity – a population-based familial coaggregation study in Sweden. Journal of child psychology and psychiatry, 58 (6): 711-718. https://www.ncbi.nlm.nih.gov/pubmed/28121008

3: Du Rietz, Coleman, Glanville, Wan Choi, O’Reilly & Kuntsi (2018) Association of Polygenic Risk for AttentionDeficit/Hyperactivity Disorder With Co-occurring Traits and Disorders. Biological Psychiary CNNI, in press. https://www.sciencedirect.com/science/article/pii/S2451902217302318?via%3Dihub