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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We have discussed the association between ADHD and obesity in our first blog (https://newbrainnutrition.com/adhd-and-obesity-does-one-cause-the-other/), briefly summarized, evidence from various study designs suggested that shared etiological factors might contribute to the above association. Recently, a large genome-wide association study (GWAS) on risk genes for ADHD reported a significant genetic correlation between ADHD and a higher risk of overweight and obesity, increased BMI, and higher waist-to-hip ratio, which further supported that there could be genetic overlap between obesity and ADHD (1).

Considering the previously described occurrence of unhealthy dietary intake in children and adolescents with ADHD in our second blog (https://newbrainnutrition.com/unhealthy-diets-and-food-addictions-in-adhd/), along with the fact that bad eating behaviours are crucial factors for the development of obesity, We can speculate that the shared genetic effects between ADHD and unhealthy dietary intake may also explain the potential bidirectional diet-ADHD associations. Is there any available evidence to support the above hypothesis?

To date, dopaminergic dysfunctions underpinning reward deficiency processing (or neural reward anticipation), was reported as a potential shared biological mechanism, through which the genetic variants could increase both the risk for ADHD and unhealthy dietary intake or obesity. Via the Gut-Brain axis, a two-way and high-speed connection, the gut can talk to the brain directly. According to the study (2), a higher proportion of bacteria that produce a substance that can be converted into dopamine was found in the intestines of people with ADHD than those without ADHD. Using functional magnetic resonance imaging (fMRI), they further found that the participants with more of these bacteria in their intestines displayed less activity in the reward sections of the brain, which constitutes one of the hallmarks of ADHD. We are therefore proposing the idea that there could be a biological pathway- ‘dietary habits-gut (microorganism)-reward system (dopamine)-ADHD’, through which the shared genetic effects between ADHD and unhealthy dietary intake may play a role.

In order to determine whether the genetic overlap between ADHD and dietary habits actually exists, we will in our next Eat2beNice project use twin methodology and unique data from the Swedish Twin Register. We will keep you updated!

This was co-authored by Henrik Larsson, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

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. Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature genetics. 2019;51(1):63.

2. Aarts E, Ederveen TH, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017;12(9):e0183509.

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated prevalence rate of 5.3% among children and of about 2.5% among adults. It is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity, being associated with significant impairment of social, academic, and occupational functioning across the lifespan.

However, despite many efforts, the exact etiology of ADHD still remains unknown and data about modificable risk and protective factors are largely lacking. Recent evidence has suggested an association between inflammation, immunological disturbances and ADHD. Supporting this idea, an increased incidence of immune-mediated disorders (e.g. asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, psoriasis, thyrotoxicosis or type 1 diabetes) accompanied by elevated serum/plasma and cerebrospinal levels of inflammatory markers (especially interleukin (IL)-6) or auto-antibody levels (e.g. antibasal ganglia antibodies, antibodies against the dopamine transporter) have been found in these patients.

Importantly, recent studies have shown the gut flora as an important immunoregulator (1-3) and it is hypothesized that an imbalance in the gut microbiota (dysbiosis) may have a negative effect on cerebral development and behavior (4). About 95% of all circulating serotonin, dopamine or noradrenaline precursors are produced by our gut microbiota, being this ‘enteric nervous system’ bidirectional connected to the central nervous system through hormonal or immune/inflammatory pathways.

In line with this, recent findings suggest that some aliments as probiotics can not only revert dysbiosis, but also modulate brain neurodevelopment, activity and improve cognition, mood and behavior due to their immunoregulatory and anti-inflammatory properties (5-7).

Therefore, understanding the microbiota and how the gut connects to the brain would be important both for the better comprehension of the biological bases that underlie some psychiatric disorders such as ADHD, as for the future development of new evidenced-based drugs for these conditions.

This was co-authored by Josep Antoni Ramos-Quiroga, MD PhD psychiatrist and Head of Department of Psychiatry at Hospital Universitari Vall d’Hebron in Barcelona, Spain. He is also professor at Universitat Autònoma de Barcelona.

REFERENCES:

1. Felix KM, Tahsin S, Wu HJ. Host-microbiota interplay in mediating immune disorders. Ann N Y Acad Sci. 2018; 1417(1):57-70.

2. Yadav SK, Boppana S, Ito N, Mindur JE, Mathay MT, Patel A, et al. Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood. Proc Natl Acad Sci U S A.2017; 114(44): E9318-27.

3. Mandl T, Marsal J, Olsson P, Ohlsson B, Andreasson K. Severe intestinal dysbiosis is prevalent in primary Sjögren’s syndrome and is associated with systemic disease activity. Arthritis Res Ther.2017;19(1):237.

4. Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016; 21(6):738-48.

5. Slykerman RF, Kang J, Van Zyl N, Barthow C, Wickens K, Stanley T, et al. Effect of early probiotic supplementation on childhood cognition, behavior and mood. A randomized, placebo-controlled trial. Acta Paediatr.2018; 107(12):2172-78.

6. Kane L, Kinzel J. The effects of probiotics on mood and emotion. JAAPA. 2018; 31(5):1-3.

7. Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci.2011;12(8):453-66

 

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Our body is colonized by trillions of microorganisms that are important for vital processes. Gut microbiota are the microorganisms living in the intestinal gut and play an essential role in digestion, vitamin synthesis and metabolism, among others. The mouth and the large intestine contain the vast majority of gut microbiota whether the stomach only contains few thousands of microorganisms, especially due to the acidity of its fluids. Microbiota composition is constantly changing, affecting the well-being and health of the individual.

Each individual has a unique microbiota composition, and it depends on several factors including diet, diseases, medication and also the genetics of the individual (host) (Figure). Some medicines, especially antibiotics, reduce bacterial diversity. Strong and broad spectrum antibiotics can have longer effects on gut microbiota, some of them up to several years. Genetic variation of an individual also affects the microbiota composition, and the abundance of certain microorganisms is partly genetically determined by the host.

The main contributor to gut microbiota diversity is diet, accounting for 57% of variation. Several studies have demonstrated that diet’s composition has a direct impact on gut microbiota. For example, an study performed on mice showed that “Western diet” (high-fat and sugar diet), alters the composition of microbiota in just one day! On the other hand, vegetarian and calorie restricted diet can also have an effect on gut microbiota composition.

Prebiotics and probiotics are diet strategies more used to control and reestablish the gut microbiota and improve the individual’s health. Probiotics are non-pathogenic microorganisms used as food ingredients (e.g. lactobacillus present in yoghurt) and prebiotics are indigestible food material (e.g. fibers in raw garlic, asparagus and onions), which are nutrients to increase the growth of beneficial microorganisms.

In the last years the new term psychobiotics has been introduced to define live bacteria with beneficial effects on mental health. Psychobiotics are of particular interest for improving the symptomatology of psychiatric disorders and recent preclinical trials have show promising results, particularly in stress, anxiety and depression.

Overall, these approaches are appealing because they can be introduced in food and drink and therefore provide a relatively non-invasive method of manipulating the microbiota.

AUTHORS:
Judit Cabana-Domínguez and Noèlia Fernàndez-Castillo

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How do you eat in a healthy fashion?  Anne Siegl, PhD writes that a big part about eating healthy is nutritional diversity.  Not eating the same thing every day, but providing your body with a rich variety of all kinds of foods and nutrients.  Part of our objective is to keep our gut happy, because our gut drives so much of our health.  And we are discovering that the gut is in continual high-speed two-way communication with the brain.  If the bacteria (microbiota) in your gut are happy, you will lead a more healthy physical life, and we are learning, a more healthy mental life as well.  We are one organism, and it’s all connected.  Keep your gut microbiota healthy with a varied diet.

Download this important report today.

 

 

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Scientific Research has now shown there is a direct connection between your Gut and your Brain.  It’s a two-way, high-speed connection, and your Gut and Brain are in constant communication.  Part of what makes up your gut is microbiota, and these tiny organisms perform important tasks in the body, such as digesting and supplying vital nutrients for both body and brain functioning.  We now know that the health of your gut not only determines your physical health, but has a direct effect on your mental health.

Our New Brain Nutrition researchers are conducting new research on these communication mechanisms and the effect on mental health.
Download your copy of The Gut Brain Axis today, and stay up-to-date on all we are learning.

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A little while ago, this blog featured an entry by Annick Bosch on the TRACE study, an amazing intervention study using the Elimination Diet to treat ADHD in kids (https://newbrainnutrition.com/adhd-and-elimination-diet/). Very shortly summarized, the Elimination Diet entails that participants can only eat a very restricted set of foodstuffs for several weeks, which can greatly reduce the number of ADHD symptoms in some kids. Subsequently, new foodstuffs are added back into the diet one by one, all the time checking that ADHD symptoms do not return. This ensures that every child for which the Elimination Diet proves successful ends up with a unique diet which suppresses their ADHD symptoms.

Now this is a fascinating study, since it indicates a direct influence of diet on ADHD behavior. What we know from the neurobiology of ADHD, is that it is caused by a myriad of relatively small changes in the structure, connectivity and functioning of several brain networks 1. For the most common treatments of ADHD, like medication with methylphenidate 2, we can quite accurately see the changes these interventions have on brain functioning. However, for the Elimination Diet, this has not been studied before at all. This is why we are now starting with the TRACE-MRI study, where kids that participate in a diet intervention in the TRACE program, are also asked to join for two sessions in an MRI scanner. Once before the start of the diet, and once again after 5 weeks, when the strictest phase of the Elimination Diet concludes. In the MRI scanner, we will look at the structure of the brain, at the connectivity of the brain, and at the functioning of the brain using two short psychological tasks. We made a short vlog detailing the experience of some of our first volunteers for this MRI session.

 

 

With the addition of this MRI session, we hope to be able to see the changes in brain structure and function over the first 5 weeks of the diet intervention. This will help us establish a solid biological foundation of how diet can influence the brain in general, and ADHD symptoms specifically. It can also show us if the effect of the Elimination Diet is found in the same brain networks and systems which respond to medication treatment. And lastly, we can see if there is a difference in the brains for those participants for whom the diet has a strong effect versus those where the diet does little or nothing to improve their ADHD symptoms. This can then help us identify for which people a dietary intervention would be a good alternative to standard treatment.

We will update you on the TRACE-MRI study and on the developments in this field right here on this blog!

 

REFERENCES
Faraone, S. V et al. Attention-deficit/hyperactivity disorder ­­­. Nat. Rev. Dis. Prim. 1, (2015).

Konrad, K., Neufang, S., Fink, G. R. & Herpertz-Dahlmann, B. Long-term effects of methylphenidate on neural networks associated with executive attention in children with ADHD: results from a longitudinal functional MRI study. J. Am. Acad. Child Adolesc. Psychiatry 46, 1633–41 (2007).

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When Alice’s mother first contacted our team to get more information on the dietary intervention at New Brain Nutrition, she mentioned that her daughter seems to be on edge all the time. On a typical day, Alice would be triggered easily over seemingly small things and stay upset for a long time. She told us that these emotional problems caused not only very strained and cheerless moments on the weekends and evenings, they also interfered notably with Alice’s social life. In between her angry or sad moments, Alice seems to be a perfectly happy and energetic 11-year old. Alice’s attention problems didn’t obstruct a healthy didactic development since she started ADHD-medication. However, the emotional problems were still present and seemed to cause severe impairment in social interactions, within the family and with peers. Therefore, her mother asked: Could we please try a dietary intervention to see if Alice’s nutrition may play a role in these problems?

Faraone[1] distinguishes two features in these kind of emotional problems: Emotional Impulsivity and Deficient Emotional Self-Regulation. Some children may experience explosive anger but also recover quickly from it. These children experience high Emotional Impulsivity but low Deficient Emotional Self-Regulation. Alice however, based on her mother’s narrative, seems to experience both high Emotional Impulsivity and high Deficient Emotional Self-Regulation.

The second week into the Elimination Diet treatment, the researcher checks in with the family: She’s still edgy and irritable for most of the time, her mother says, but she seems to break out of it a whole lot sooner. The other day her brother Daniel came home, telling Alice he ate lots of non-elimination diet snacks at his friend’s house. Understandably, Alice became upset but it didn’t last as long as her parents expected. In other words: The Emotional Impulsivity hadn’t decreased yet, but the Deficient Emotional Self-Regulation had.

By the end of the first 5 weeks of the dietary intervention, Alice’s parents reported a convincing decrease in emotion regulation problems. The teacher also reported that the attention problems had stabilized, as much as they did with the ADHD-medication that Alice had before. The family decided to continue the Elimination Diet and start with the re-introduction phase. Every two weeks a new product was re-introduced to see if this may elicit symptoms. This was probably the most interesting period for the family, as emotion regulation problems and attention problems arose and subsided over different phases.

After one year, Alice and her family had figured out a set of foods that, when eliminated from her diet, helped diminishing both the attention problems and emotional problems. Alice is less responsive to emotional triggers and more balanced during social interactions. Alice’s personalized diet or personalized nutrition is based on her experiences and symptoms during the dietary intervention. Her mother is very glad that they discovered this lifestyle intervention as an alternative to their previous treatment with ADHD-medication.

Writers note: This is the story of one individual participating in the New Brain Nutrition study. Evaluating the role of nutrition in treatment of mental health with scientific evidence is part of our future.

More information can be found in [1] Faraone S.V., Rostain A.L., Blader J., Busch B., Childress A.C., Connor D.F., & Newcorn J.H. (2018). Practitioner Review: Emotional dysregulation in attention‐deficit/hyperactivity disorder – implications for clinical recognition and intervention. Journal of Child Psychology and Psychiatry. https://doi.org/10.1111/jcpp.12899

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In my previous blogs, I explained the research questions of my study. This study will be performed in two cohorts which I will elaborate on in this current blog about early life nutrition and studying gut microbiota. The cohorts are called BIBO and BINGO.  

BIBO stands for ‘Basale Invloeden op de Baby’s Ontwikkeling’ (in English: basal influences on  infant’s development). Recruitment of this cohort started in 2006, and a total of 193 mothers and their infants were included. At age 10, 168 mothers and their children still joined the BIBO study; the attrition rate is thus low. The majority of the mothers are highly educated (76%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. A unique aspect of the BIBO study is the number of stool samples collected in early life. Also, detailed information about early life nutrition has been recorded during the first six months of life (e.g. information on daily frequency of breastfeeding, formula feeding, and mixed feeding). Together, these stool samples and nutrition diaries provide important insights in the relations between early life nutrition and gut microbiota development. Data about children within the BIBO cohort will be collected at age 12,5 years and 14 years. At 12,5 years, the participants will be invited to the university for an fMRI scan (more information about the fMRI scan will be given in a future blog). At age 14, children’s impulsive behavior will be assessed by means of behavioral tests and (self- and mother-report) questionnaires.

BINGO stands for ‘Biologische INvloeden op baby’s Gezondheid en Ontwikkeling’ (in English: biological influences on infant’s health and development). When investigating biological influences on infant’s health and development, it is important to start before birth. Therefore, 86 healthy women were recruited during pregnancy. Recruitment took place in 2014 and 2015. One unique property of the BINGO cohort is the fact that not only mothers were recruited, but also their partners. The role of fathers is often neglected in research, and thus an important strength of this BINGO cohort. Another unique property is that samples of mothers’ milk were collected three times during the first three months of life, to investigate breast milk composition. As for many infants their diet early in life primarily consists of breast milk, it is interesting to relate breast milk composition to later gut microbiota composition and development. Currently, 79 mothers and children, and 54 fathers are still joining the BINGO study. The average age of the participants at the time of recruitment was 32 years for mothers and 33 years for the father. Majority of the parents within this cohort are highly educated (77%) and from Dutch origin (89%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. At age 3, children’s impulsive behavior will be assessed by means of behavioral tests and mother-report questionnaires.

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Why 12 genetic markers for ADHD are exciting news for New Brain Nutrition

We are finally here: for the first time, genome-wide significant markers are identified that increase the risk for Attention Deficit / Hyperactivity Disorder (ADHD). This research was conducted by an international consortium of more than 200 experts on genetics and ADHD, and includes several researchers that are also involved in our Eat2beNICE project (the scientific basis of this New Brain Nutrition website). The findings were recently published in the prestigious journal “Nature Genetics” and will greatly advance the field of ADHD genetics research.

Why is this finding so important?

The genetics of ADHD are very complex. While ADHD is highly heritable, there are likely to be thousands of genes that contribute to the disorder. Each variant individually increases the risk by only a tiny fraction. To discover these variants, you therefore need incredibly large samples. Only then can you determine which variants are linked to ADHD. The now published study by Ditte Demontis and her team combined data from many different databases and studies, together including more than 55,000 individuals of whom over 22,000 had an ADHD diagnosis.

We can now be certain that the twelve genetic markers contribute to the risk of developing ADHD. Their influence is however very small, so these markers by themselves can’t tell if someone will have ADHD. What’s interesting for the researchers is that none of these markers were identified before in much smaller genetic studies of ADHD. So this provides many new research questions to further investigate the biological mechanisms of ADHD. For instance, several of the markers point to genes that are involved in brain development and neuronal communication.

Why are our researchers excited about this?

A second important finding from the study is that the genetic variants were not specific to ADHD, but overlapped with risk of lower education, higher risk of obesity, increased BMI, and type-2 diabetes. If genetic variants increase both your risk for mental health problems such as ADHD, and for nutrition-related problems such as obesity and type-2 diabetes, then there could be a shared biological mechanism that ties this all together.

We think that this mechanism is located in the communication between the gut and the brain. A complex combination of genetic and environmental factors influence this brain-gut communication, which leads to differences in behaviour, metabolism and (mental) health.genetic markers for adhd

The microorganisms in your gut play an important role in the interaction between your genes and outside environmental influences (such as stress, illness or your diet). Now that we know which genes are important in ADHD, we can investigate how their functioning is influenced by environmental factors. For instance, gut microorganisms can produce certain metabolites that interact with these genes.

The publication by Ditte Demontis and her co-workers is therefore not only relevant for the field of ADHD genetics, but brings us one step closer to understanding the biological factors that influence our mental health and wellbeing.

Further Reading

Demontis et al. (2018) Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. https://www.nature.com/articles/s41588-018-0269-7

The first author of the paper, Ditte Demontis, also wrote a blog about the publication. You can read it here: https://mind-the-gap.live/2018/12/10/the-first-risk-genes-for-adhd-has-been-identified/

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