Recently, I participated in the Radboud Talks 2019, a scientific pitch competition, where I was lucky to be one of the eight finalists.

Why Radboud Talks? It is a perfect opportunity to share my work/ideas with the world and to gain more experience regarding presentation skills. They organized two workshops beforehand, where I had the opportunity to learn presentation techniques from professionals (actors and science communication advisors). We also received a lot of feedback, so I really learned a lot about how to present my scientific work to a general audience.

Below you can find the video from the preliminaries based on which I was chosen as a finalist. There you can hear about my research project which is about gut bacteria and their potential role in ADHD (Attention Deficit Hyperactivity Disorder). ADHD is a common worldwide neurodevelopmental disorder. Every person with ADHD has a unique combination of symptoms and challenges. Importantly, it has a significant social impact on patients’ lives, causing disruption at school, work and relationships. Despite its societal importance, progress in understanding disease biology has been slow.

 

The study of the human microbiome has become a very popular topic, because of their revealed importance in human physiology and health maintenance. Numerous studies have reported that gut bacteria may have an effect on our mental health. Some studies showed a potential role of gut bacteria in a psychiatric disorder like depression, autism or Parkinson (1). Above all, diet showed to have a profound effect of ADHD symptoms. This was earlier described in this blog: https://newbrainnutrition.com/investigating-the-effects-of-a-dietary-intervention-in-adhd-on-the-brain/ and we know that diet is one of the main factors influencing gut bacteria. Taking all together, I am curious (and investigating) if gut bacteria play a role in ADHD and if yes what kind of effect do they have on ADHD symptoms.

REFERENCES:
Bastiaanssen, T., Cowan, C., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2018). Making Sense of … the Microbiome in Psychiatry. The international journal of neuropsychopharmacology22(1), 37–52. doi:10.1093/ijnp/pyy067

 

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In every classroom, approximately two children are diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). They struggle with attention problems and hyperactive and impulsive behavior. This has negative consequences for these children. For example, they can have difficulties learning, it puts them at risk for other psychiatric problems, and it can cause parent-child relationship problems. Therefore, children with ADHD do need some sort of treatment for optimizing the quality of their lives.

After psycho-education to the child, parents and teacher, medication is often the first choice of treatment because it is evidence-based. However, there is a growing group of parents that do not wish to medicate their child. They are concerned about the side and long-term effects. Thus, these parents seek other treatment. That is where they get stuck: which other effective treatments are available?

In order to develop new treatments, there is a growing field of research focusing on risk factors for ADHD symptoms. One of these risk factors that has been studies increasingly is nutrition. Nutrition plays a role in physical well-being, but could also play a role in psychological well-being and cognitive functioning. Consequently, dietary treatments could be an alternative treatment for children with ADHD. There is a long history of research in nutrition, but there is not enough evidence yet about the cost-effectiveness to implement dietary treatments in clinical health care.

So far, studies examining the effectiveness of a so-called elimination diet showed the strongest effects (1). The aim of an elimination diet is to find out which products trigger ADHD symptoms. However, results of these studies are inconclusive because of several limitations. First, outcome measurements used in these studies were not objective. Second, studies suffered from a sample bias towards highly motivated and educated parents. Third, underlying mechanisms are still unknown. Fourth, long-term effects are unknown. Moreover, it is unknown if an elimination diet is more effective in reducing ADHD symptoms than a healthy diet based on the World Health Organization (WHO) guidelines (2).

We thought: can we take into account these limitations ánd examine the effectiveness of two dietary treatments? This resulted in the TRACE study: ‘Treatment of ADHD with Care as usual versus an Elimination diet’ (TRACE) study. This is the first study to determine the short- and long-term effectiveness and cost-effectiveness of two dietary treatments as initial addition to care as usual as a treatment trajectory for children with ADHD. We will substantially improve upon previous studies by implementing the intervention in non-commercial mental health centers, including blinded and objective measurements, and comparing two dietary treatments with care as usual. Also, understanding the biological effects could inform clinicians to potential markers and targets for preventative or individualized treatment. For this reason, we also examine the underlying biological mechanisms (e.g. mechanisms in the gut and brain) of dietary treatments (TRACE-BIOME and TRACE-MRI studies). We collect blood, stool and saliva samples.

The TRACE study is a two-arm randomized control trial: participants are randomized to either an elimination diet or a healthy diet. The comparator arm includes children who are being treated with care as usual. Currently, we included in each dietary treatment arm about half of the targeted participants (N=81 in each dietary group). In the care as usual group, we included about one-third of the targeted participants (N=60). We hope to finish inclusion around January 2020.

I am really looking forward to the results and hope to share this with you in a couple of years! If you have any questions, feel free to contact us via trace@karakter.com

REFERENCES
(1) Nigg, J. T., Lewis, K., Edinger, T., & Falk, M. (2012). Meta-analysis of attention- deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives. Journal of the American Academy of Child & Adolescent Psychiatry, 51(1), 86-97. https://doi.org/10.1016/j.jaac.2011. 10.015 .
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321798/

(2) Izquierdo Pulido, M. L., Ríos Hernández, A., Farran, A., & Alda, J. Á. (2015). The role of diet and physical activity in children and adolescents with ADHD. Recent Advances in Pharmaceutical Sciences V, 2015, Research Signpost. Chapter 4, p. 51-64.
Link: http://diposit.ub.edu/dspace/bitstream/2445/67543/1/T_1444299316Munozv%204.pdf

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Loss of appetite is among the most common side effects of stimulant for ADHD. Across studies, approximately 20% of patients with ADHD who were treated with stimulants reported a loss of appetite [1,2]. Weight loss is also quite common, as are digestive problems [3]. Together, such side effects are often referred to as “gastro-intestinal adverse events”. But why do stimulants change the way we go about eating? And what could this tell us about ADHD itself?

Appetite can arise in response to physical cues, such as an empty stomach or low blood sugar. Psychological cues can also influence our appetite; for instance, we may get hungry when we watch other people eat, or when we are bored. For most people, eating is a pleasant and rewarding activity. In the human brain, pleasure, reward, craving and, thus, appetite, have everything to do with dopamine. More specifically, with dopamine levels in the striatum, a cluster of neurons at the very base of the forebrain. The striatum is strongly connected with the prefrontal cortex. The prefrontal cortex exercises cognitive control over the urges of the striatum: when we’re hungry, the striatum makes us crave high-caloric, high-fat, or sweet foods; at the same time, our more rational prefrontal cortex helps us make responsible food choices.

Interestingly, ADHD also has everything to do with dopamine and the striatum. Dopamine levels in the striatum are slightly ‘off’ in individuals with ADHD. As a result, people with ADHD feel a higher urge to seek pleasant experiences, and less prefrontal control over this urge. Impulsivity, a prominent feature of ADHD, can be viewed as a failure to sufficiently activate the prefrontal cortex. Finding a balance between pleasure-seeking on the one hand, and rational decision-making on the other, can be difficult for all of us. However, for people with ADHD whose dopamine balance is slightly off, making healthy, non-impulsive decisions about what to eat may be even more challenging. Indeed, overweight, obesity and diabetes seem to be more common in people with ADHD compared to people without ADHD [4].

Stimulants such as methylphenidate and dexamphetamine can restore the dopamine balance in the brain. This may result in less craving for food (as well as for other pleasant activities) and more control over impulsive urges. It is thus not very surprising that stimulant medications may cause a loss of appetite or even weight loss. Interestingly, stimulants are sometimes used to treat obesity and certain eating disorders as well. Especially for eating disorders involving impulsive eating, such as bulimia nervosa and binge-eating disorder, stimulant treatment could be promising. [5]

There is one other interesting angle on stimulants, dopamine, and eating. Did you know that most of the dopamine in your body is not located in the brain? In fact, a substantial proportion of all dopamine-related processes in the human body take place in the gut. Throughout the gastro-intestinal tract, dopamine receptors are abundant. Therefore, in addition to the indirect effects described above (i.e., via craving and/or impulse control), stimulants may have direct effects on eating behaviours as well. Unfortunately, we know very little about such direct effects.

REFERENCES
[1] Storebø, Ramstad, Krogh, Nilausen, Skoog, Holmskov et al. (2015). Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. Cochrane Database Syst Rev (11):CD009885. doi: 10.1002/14651858.CD009885.pub2

[2] Storebø, Pedersen, Ramstad, Kielsholm, Nielsen, Krogh et al. (2018) Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents – assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev 5:CD012069. doi: 10.1002/14651858.CD012069.pub2

[3] Holmskov, Storebø, Moreira-Maia, Ramstad, Magnusson, Krogh et al. (2017) Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. PLoS One 12(6):e0178187. doi: 10.1371/journal.pone.0178187

[4] Cortese, Moreira-Maia, St Fleur, Morcillo-Peñalver, Rohde & Faraone (2016). Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis. Am J Psychiatry 173(1):34-43. doi: 10.1176/appi.ajp.2015.15020266

[5] Himmerich & Treasure (2018). Psychopharmacological advances in eating disorders. Expert Rev Clin Pharmacol, 11(1):95-108. doi: 10.1080/17512433.2018.1383895

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