Meet Tim: he is an 8-year-old boy, living in the Netherlands with his parents and younger sister. A couple of years ago, Tim was diagnosed with Attention Deficit Hyperactivity/Impulsivity Disorder (ADHD). His psychologist recommended to participate in the TRACE study: this study examines the short- and long term effects of dietary treatments in children with ADHD. In addition, the TRACE-BIOME study examines the underlying mechanisms of a dietary treatment. For this, we collect blood, stool, and saliva samples and we perform a fMRI. These measurements might, among other things, shed light on the role of the brain-gut-axis.

But what’s it like to participate in a scientific study? First of all, Tim was allocated to one of the two TRACE dietary treatments: an elimination diet or a healthy diet. Tim was allocated to the elimination diet. If we want to know if this diet is effective for Tim, we have to do a lot of different assessments (Figure 1).

Figure 1: assessments TRACE study

 

 

           

 

 

 

 


Before the baseline, 5 week and 1-year assessments, a couple of measurements already take place:

  • Tim wears an Actigraph one week before the assessment, which measures motor activity and sleep-wake rhythm;
  • Parents collect a stool sample from Tim in which his microbiota can be assessed;
  • Parents and teachers fill out different questionnaires about Tim’s behavior, but also about, for example, parenting styles;
  • Parents keep track of a food diary: what does Tim eat during two weekdays and one weekend day?

Before starting the elimination diet, Tim’s parents have a consult with one of the TRACE dieticians, so that they can prepare changing the diet of Tim. Then, it is time for the baseline assessment. Tim and his mother meet the researcher at the hospital for the blood venipuncture. He also has to chew on a cotton pad to collect a saliva sample. After this, they walk to Karakter which is a center for Child and Adolescent Psychiatry. The researcher measures his weight, length, blood pressure and heart rate. Next, Tim has to perform a task on the laptop which he really likes! This task assesses cognitive functions such as sustained attention, working memory, and cognitive flexibility. After the computer task, there is time for a break. Next, they start with behavioral observation. In this task, Tim first plays with his mother and then with the researchers. The different tasks try to elicit ADHD symptoms and emotion (dys)regulation behavior. Finally, the MRI researcher takes Tim and his mother to the fMRI scanner in which he has to do two different tasks. All in all, the assessment takes about 4 hours.

After 5 weeks of the diet, it is time for the second assessment which is the same as the baseline assessment. The researcher has calculated, based on the parent and teacher questionnaires, if there is a significant response to the diet. Tim shows a 40% reduction of ADHD symptoms, which is a significant response! Therefore, they continue the diet. After 4 and 8 months of the diet, his parents receive some online questionnaires. Finally, after one year they are invited for the final assessment, which is again the same as the baseline assessment (without the fMRI).

The following movie explains the assessments described above, in Dutch: 

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Twin studies have been used for decades to estimate the relative importance of genes and environments for traits, behaviors and disorders. A very large meta-analysis of all twin studies conducted during the past 50 years (almost 3000 publications) revealed that across all studied traits the average reported heritability was 49%, meaning that about 50% of the variation in traits is due to genetic factors (1).

1. Methods and theory of classical twin design

By comparing the differences and similarities between twins, researchers use them as a natural experiment to study whether a trait, phenotype or disease is due to nature (genetic predisposition) or nurture (environmental factors).

In order to get a better understanding of twin studies, one must first understand the two types of twins:

  • Monozygotic (MZ) or identical twins were conceived in a single egg, which split and forms two embryos. Therefore, MZ twins share all their genes (100%), and are definitely the same sex.
  • Dizygotic (DZ) or fraternal twins were developing from a separate egg and each egg is fertilized by its own sperm cell, and therefore sharing on average 50% of their genes. DZ twins could be of the same sex or different sex.

Based on the different degree of genetic and the similar extent of prenatal and later environmental factors sharing between MZ and DZ twins, MZ twin pairs may show a higher similarity on a given trait, as compared with DZ twins, if genes significantly influence that trait. On the other hand, if MZ and DZ twin pairs share a trait to an equal extent, it is likely that the environment influences the trait more than genetic factors.

The similarity for a given trait is estimates via intra-class correlations (ICC), and similarity across different traits by the cross-twin cross-trait correlations (CTCT). Comparison of correlations across MZ and DZ pairs allows for the variance (V) of a given trait to be decomposed into three factors:

  • Genetic factors, including additive genetic factors (A), and dominant genetic factors (D)
  • Shared environmental factors (C), that is events that happen to both twins, affecting them in the same way. For example, the socio-economic status of the family, the general personality and general parenting styles and beliefs of the parents.
  • Non-shared or unique environmental factors (E), that is events happen to one twin but not the other one, or the events affect either twin in a different way. For example, school and classroom environment, also including measurement error.

Under then assumptions of no interaction and no covariance between A, C, D, and E, the total variance of a phenotype (P) can be expressed as:

𝑉𝑎𝑟,𝑃.=𝐴+𝐷+𝐶+𝐸

Narrow sense heritability is defined as the proportion of variance in a trait due to additive genetic effects (A):

,-2.=,𝑉𝑎𝑟(𝐴)-𝑉𝑎𝑟(𝑃).

Broad sense heritability as the proportion of variance due to additive and dominance genetic effects (A+D):

,-2.=,𝑉𝑎𝑟(𝐴+𝐷)-𝑉𝑎𝑟(𝑃).

The classical twin model can be extended to explore bivariate and multivariate traits association, and test for differences between males and females by using sex-limitation models. More information on how to conduct classical and advanced twin model fitting analyses, please refer to (2) and (3).

2. Important advantages of twin studies

  • Estimate the relative importance of genetic factors (i.e., heritability) of one or more traits
  • Help identify shared genetic factors that influence different traits, behaviors and disorders.
  • Explore the causal status of environmental risk factors by controlling for genetic and shared environmental confounding.
  • Offers unique opportunities to study the gene-environmental interplay, including both gene-environmental correlations and gene-environmental interactions.

In summary, the twin study design is considered an important behavioral genetic approach that has been used in many fields, including biology, psychology and sociology. Using a substantial amount of the published twin research (and other genetic informative studies, e.g. sibling comparison, adoption studies), Plomin et al. summarized the top 10 replicated and important findings (4). These findings included:

  • All psychological traits show significant and substantial genetic influence;
  • No traits are 100% heritable, highlighting the importance of environmental factors, and
  • The heritability is caused by many genes of small effect.

Most of these findings or discoveries that could only have been found using genetically sensitive research designs.

In the Eat2BeNice project, we are currently using data from Swedish Twin Register (https://ki.se/en/research/the-swedish-twin-registry) to estimate the heritability of unhealthy eating habits and ADHD symptoms in adults, and also to investigate the relative importance of genetic, shared environmental and non-shared environmental factors for the overlap between adult ADHD symptoms and different dietary habits diets. We will also test specific hypothesis regarding gene-environmental interactions.

Authors:
Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.

Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

REFERENCES

  1. Polderman TJ, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature genetics. 2015;47(7):702-9.
  2. Neale, M. C. and Meas, H. M. Methodology for genetic studies of twins and families. and the paper Rijsdijk FV & Sham PC. (2002),
  3. Analytic Approaches to Twin Data using Structural Equation Models. Briefings in Bioinformatics, 3 (2), 119 -133.
  4. Plomin, Robert, et al. “Top 10 replicated findings from behavioral genetics.” Perspectives on psychological science11.1 (2016): 3-23.

 

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In the Eat2beNICE project, the researchers aim at studying the effect of diet and mental health and our blogs are meant to enlighten readers.

Every day research findings published in journals will offer an opinion on how to best live our lives. It is simply not possible, nor advised, to change your habit after every piece of new knowledge. On the other hand, researchers do need to publish their results in order to have their findings discussed and reproduced. How do you as a reader navigate?

No single study should alone be enough to change nutritional advice or guidelines. The research into a specific field is best understood when looking at several pieces of knowledge (or publications) as contributing to a bigger picture. Kim Tingley wrote a descriptive picture in the New York Times Magazine on how to view scientific findings. https://www.nytimes.com/2019/05/16/magazine/how-much-alcohol-can-you-drink-safe-health.html Here he writes that the process of understanding the contribution of scientific research should be like looking through a lens and asking yourself if it is clearer or less clear with this particular piece of new information.

Interpreting results from a study isn’t always easy and the limitations of the study can sometimes be difficult to spot. If you are feeling bombarded by the media with constant new findings, be aware that single findings are one piece of information, usually not the full picture and should be interpreted as such. For more information on matters of interests, a good place to start is looking at literature reviews or in the Cochrane Library https://www.cochranelibrary.com/ which will offer views on important publications within a field and help you interpret status quo.

REFERENCES

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Food is not only essential for our bodily functions, but also for our brain functioning and associated behavioural performance. Some studies have shown that eating more of a certain nutritional compound can enhance your performance. But is it really that simple? Can food supplements support our performance? While performing studies on the micronutrient tyrosine, I found out that it is not that simple, and I will tell you why.

Your food contains a range of nutrients that your body uses amongst others as energy sources and as building blocks for cells. For example, protein-rich food such as dairy, grains and seeds are made up of compounds called amino acids. Amino acids are used for different purposes in your body. Muscles use amino acids from your diet to grow. Some people take advantage of this process to increase muscle growth by eating extra protein in combination with exercise.

But amino acids also have a very important role for brain functioning; specific amino acids such as tryptophan, phenylalanine and tyrosine are precursors for neurotransmitters. Specifically tyrosine is a precursor for the neurotransmitter dopamine, which is crucially involved in cognitive processes such as short-term memory, briefly memorizing a phone number or grocery list. Ingested tyrosine from a bowl of yoghurt or a supplement is digested in your intestines, taken up into the bloodstream and then passes through the barrier between the blood stream and the brain (the blood-brain-barrier). In neurons in the brain, tyrosine is further processed and converted into dopamine. Here, dopamine influences the strength and pattern of neuronal activity and hereby contributes to cognitive performance such as short-term memory.

Short-term memory functions optimally most of the time, but can also be challenged. For example during stressful events like an exam or when faced with many tasks on a busy day, many people experience trouble remembering items. Another example is advancing age; elderly people often experience a decrease in their short-term memory capacity. These decrements in short-term memory have been shown to be caused by suboptimal levels of brain dopamine.

The intriguing idea arises to preserve or restore optimal levels of dopamine in the brain with a pharmacological tweak, or even better, using a freely available nutritional compound. Could it be that simple? Yes and no. Yes, if you eat high amounts of tyrosine, there will be more dopamine precursors going to your brain. But the effects on short-term memory vary between individuals and experiments.

Various experiments have been conducted using tyrosine supplementation to see if cognitive performance can be preserved, with mixed success.

In groups of military personnel, negative effects of stress or sleep deprivation on short-term memory were successfully countered. Subjects were asked to take an ice-cold water bath, known to induce stress, and to perform a short-term memory task [1]. In other experiments subjects remained awake during the night or performed challenging tasks on a computer in a noisy room, mimicking a cockpit [2,3].

The group that took tyrosine before or during these stressful interventions showed less decline in their short-term memory than the group that ingested a placebo compound. Tyrosine supplementation also benefitted performance on a cognitive challenge without a physical stressor, compared with performing a simpler task. Other experiments, without a physical or cognitive stressor didn’t show any differences in performance compared with a control group.

These results show that tyrosine supplementation can benefit performance on cognitive processes, such as short-term memory, but only during challenging or stressful situations that induce a shortage of brain dopamine (for review see 4,5).

However, results have also been shown to vary with age. Experiments in elderly people showed that tyrosine also influences the most challenging task compared with simple processes, but contrary to observations in younger adults, in many older adults tyrosine decreased rather than improved performance [6,7]! It seems that the effects seen in young(er) adults no longer hold in healthy aging adults. This can be due to changes in the dopamine system in the brain with aging, as well as changes in other bodily functions, such as the processing of protein and insulin. This doesn’t mean that tyrosine supplementation should be avoided all together for older adults. The results so far suggest that dosages should be adjusted downwards for the elderly body. Further testing is needed to conclude on the potential of tyrosine to support short-term memory in the elderly.

We can conclude that nutrients affect behavior, but importantly, these effects vary between individuals. So, unfortunately, one size does not fit all. To assure benefits from nutrient supplementation or diet rather than wasteful use or unintended effects, dosages should be carefully checked and circumstances of use should be considered.

REFERENCES
O’Brien, C., Mahoney, C., Tharion, W. J., Sils, I. V., & Castellani, J. W. (2007). Dietary tyrosine benefits cognitive and psychomotor performance during body cooling. Physiology and Behavior, 90(2–3), 301–307

Magill, R., Waters, W., Bray, G., Volaufova, J., Smith, S., Lieberman, H. R., … Ryan, D. (2003). Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation. Nutritional Neuroscience, 6(4), 237–246.

Deijen, J. B., & Orlebeke, J. F. (1994). Effect of tyrosine on cognitive function and blood pressure under stress. Brain Research Bulletin, 33(3), 319–323.

van de Rest, O., van der Zwaluw, N. L., & de Groot, L. C. P. G. M. (2013). Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline. Amino Acids, 45(5), 1035–1045.

Jongkees, B. J., Hommel, B., Kuhn, S., & Colzato, L. S. (2015). Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands-A review. Journal of Psychiatric Research, 70, 50–57.

Bloemendaal, M., Froböse, M. I., Wegman, J., Zandbelt, B. B., van de Rest, O., Cools, R., & Aarts, E. (2018). Neuro-cognitive effects of acute tyrosine administration on reactive and proactive response inhibition in healthy older adults. ENeuro, 5(2).

van de Rest, O.& Bloemendaal, M., De Heus, R., & Aarts, E. (2017). Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging. Nutrients, 9(12).

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This month, August 2018, I started as dissemination manager at New Brain Nutrition. This means that I will make sure that the information generated in this research project is spread out to society. Together with the dissemination and communication team of New Brain Nutrition, I strive to inform and educate as many people as possible about how nutrition influences our gut, our brain and our mental health.

Now I didn’t study communication or marketing. Rather, I studied Cognitive Neuroscience and did a PhD on brain connectivity in adults with ADHD. But while doing this PhD research, I became very interested in science communication. I organised an open day, started a blog with fellow PhD students, and participated in science battles. And through these experiences I learned that for science communication the most important ingredient is a willingness to convey your story to someone else.

The art of storytelling is thought to be as old as humanity itself. People are better at remembering and comprehending stories [1] and stories attract more attention than what’s called ‘logical-scientific communication’ [2]. However, storytelling is often viewed as unfit for sharing scientific results, because a story provides a subjective interpretation of data [3]. In a good story, only the elements that contribute to the story are told, while the ones that do not match the narrative are left out. That surely is not what we want to do in science communication!

New Brain Nutrition Research through StorytellingHowever, I do think that scientists should use the art of storytelling in their science communication to non-expert audiences. There is just too much and too complex data and information out there. If we want people to hear about our findings, and understand what they mean, we need to help them to read, comprehend and remember this information. Narratives are often the best way to do this. When telling these stories, we need to make careful decisions about the goal of our story (do you want to persuade your audience of something, or is the goal comprehension?), the level of accuracy (can you use a metaphor that is not entirely accurate, in order to accurately describe a certain process in an understandable way?) and whether or not to leave out certain facts of the story [2]. These decisions can be difficult, and we might sometimes make the wrong decisions, but overall I believe that we can all learn the art of telling good, honest stories.

At the same time, science can be much more open and transparent about the data and the findings themselves. I therefore think that open science, including open access publications and data sharing, should go hand-in-hand with storytelling in science communication. Share your story, your interpretation of the data, with the public. Take them along in your reasoning, which you have developed over the years as an expert in your field. And at the same time, share your data and your findings so that those who want to can come up with their own interpretations and conclusions.

So that’s my goal: telling you the stories of our research. As accurately as possible, without hiding information or twisting plots, but in an interesting, engaging and comprehensible way. And I hope that this will be a dialogue rather than a monologue. Tell us what you think, what your questions are, what you find difficult to believe, what you want to know more about. Then together we can build the story of New Brain Nutrition.

This blogpost was inspired by a recent article in The Guardian: https://www.theguardian.com/commentisfree/2018/jul/20/our-job-as-scientists-is-to-find-the-truth-but-we-must-also-be-storytellers

 

References:

[1] Schank, Roger C. & Abelson, Robert P. (1995) Knowledge and Memory:  The Real Story.  In: Robert S. Wyer, Jr (ed) Knowledge and Memory: The Real Story. Hillsdale, NJ. Lawrence Erlbaum Associates.  1-85. http://cogprints.org/636/1/KnowledgeMemory_SchankAbelson_d.html

[2] Dahlstrom, Michael F. (2014) Using narratives and storytelling to communicate science with nonexpert audiences. PNAS, 201320645. https://doi.org/10.1073/pnas.1320645111

[3] Katz, Yarden (2013) Against storytelling of scientific results. Nature methods, 10 (11). https://doi.org/10.1038/nmeth.2699

 

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 728018

New Brain Nutrition is a project and brand of Eat2BeNice, a consortium of 18 European University Hospitals throughout the continent.

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