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: 

Please share and like us:
error

Facets of impulsivity – Differences between patients with BPD and ADHD
It’s more than likely you have done it before, said something reckless you later regretted or sent a quick and rude response to an email with annoying content. It means that you acted impulsively, or in other words, you had a rapid and unplanned response without appropriate foresight. If your impulsivity is persistently expressed, it can be really risky and maladaptive. However, there may have been situations in which your impulsive behavior paid off and could serve a good purpose. Has it ever occurred to you that a quick response at work was a lucky move at all, or a thoughtless purchase was eventually useful?

However, is it so black and white? Do we just have to decide whether we are impulsive or not? It’s a fact now, that impulsivity is a multifaceted trait, however, there are subtle differences between researchers in how many domains do they distinguish. So the answer is: it’s more complicated than that.

High levels of impulsivity can also be the part of different psychiatric conditions, and also a diagnostic criterion. Kenézlői and colleagues emphasize the importance of impulsivity has different characteristics with respect to the condition it’s part of. Their pilot study (2019) aimed to compare the impulsivity profile, personality traits and aggression level of patients with adult Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD) main diagnoses, and healthy control subjects. They also analyzed the role of childhood adverse events in the background of impulsive symptoms.

Comparing the aforementioned three groups, their results show that there are significant differences between the impulsivity domains: higher levels of attentional impulsivity (distractibility) and motor impulsivity (inhibition) were observed in ADHD, while non-planning impulsivity (decision-making without long consideration) was more characteristic to BPD. Besides, they found that ADHD patients reached more points on the novelty seeking, harm avoidance, reward dependency, perseverance, self-direction and the cooperation subscales than BPD patients. Regarding the aggression regulation, there was no difference in the physical aggression and hostility scores, however, BPD participants rated themselves verbally less aggressive than ADHD participants and healthy controls. Another notable outcome is that ADHD patients reached more points on anger scale and higher total scores than healthy controls, while this difference wasn’t significant with BPD patients. According to the findings, the more emotionally neglected the milieu where a person grows up, the more chance to have higher levels of impulsivity in adulthood.

Taken together, impulsivity is a heterogeneous phenomenon and more research in this field could help us to understand the etiology of different psychiatric conditions, which can result in effective and more specific therapeutic interventions.

At the time of writing, the full research article is not available online.

REFERENCES:
Kenézlői, E., Balogh, L., Fazekas, K., Bajzát, B., Kruk, E., Unoka, Zs., & Réthelyi, J. (2019). Transdiagnostic study of impulsivity dimensions. Comparative analysis of impulsivity profiles in adult Attention Deficit Hyperactivity Disorder and Borderline Personality Disorder.

 

Please share and like us:
error

Mens sana in corpore sano – healthy mind and healthy body

Food insecurity – defined as an individual or household lacking access to sufficient, safe, and nutritious food that meets individuals’ dietary needs – has been linked to children’s behavioral, academic, and emotional problems and an increased risk of the development of mental health disorders [1, 2].

In a Canadian study on food insecurity in young children, researchers found that children from food-insecure families were disproportionately likely to experience persistent symptoms of hyperactivity and inattention. These results were still true after controlling for immigrant status, family structure, maternal age at child’s birth, family income, maternal and paternal education, prenatal tobacco exposure, maternal and paternal depression and negative parenting [3].

Accordingly, a systematic review on food insecurity and attention-deficit hyperactivity disorder (ADHD) symptoms in children reported a predictive and inverse relationship between the two, with possible lasting impacts into adulthood. Authors concluded that evidence exists to hypothesize that childhood food insecurity is associated with predisposing or exacerbating ADHD symptoms in children [4].

In 2017 Dr. Raju, President of the Indian Psychiatric Society concluded in a speech on medical nutrition in mental health and disorders that there is growing evidence for a relationship between quality of diet and mental health. According to Raju, the importance of nutrients as important agents for prevention, treatment, or augmentation of treatment for mental disorders has been established. “Empathic interactions and rational nutrition along with specific pharmacological and physical interventions could form an ideal and humane patient-friendly package in psychiatric practice” [5].

Therefore, identifying families in risk of food insecurity and getting children and adolescents the best possible food supply could result in fewer children with ADHD symptoms.

REFERENCES:

  1. Althoff, R.R., M. Ametti, and F. Bertmann, The role of food insecurity in developmental psychopathology. Prev Med, 2016. 92: p. 106-109.
  2. Shankar, P., R. Chung, and D.A. Frank, Association of Food Insecurity with Children’s Behavioral, Emotional, and Academic Outcomes: A Systematic Review. J Dev Behav Pediatr, 2017. 38(2): p. 135-150.
  3. Melchior, M., et al., Food insecurity and children’s mental health: a prospective birth cohort study. PLoS One, 2012. 7(12): p. e52615.
  4. Lu, S., et al., The Relationship between Food Insecurity and Symptoms of Attention-Deficit Hyperactivity Disorder in Children: A Summary of the Literature. Nutrients, 2019. 11(3).
  5. Raju, M., Medical nutrition in mental health and disorders. Indian J Psychiatry, 2017. 59(2): p. 143-148.
Please share and like us:
error

Neurodevelopmental disorders such as attention deficit disorder (ADHD), autism spectrum disorder (ASS) and different types of anxiety disorders are associated with a higher risk of poor dietary, physical activity and sleep habits. Shaping behavior in children with neurodevelopmental symptoms can be challenging. How do parents experience shaping healthy habits in these children? What are tips and tricks to encourage your child to live healthy? We took together the results of a recent study conducted in Boston and our own results from a qualitative interview with parents of children that followed the TRACE-diet to help you encourage your child to be healthy.

What is hard?
For parents of children with a neurodevelopmental disorder (ND) it can be challenging to convince their children to make healthy choices. Some parents explain that taking an unhealthy option from a neurotypical child might also lead to an anger meltdown, but this meltdown is not comparable with a ND meltdown, which can last the whole day. Furthermore, children with ND can be more impulsive, which makes it harder for them to think before they choose. Other children with ND are resistant to change, and/or lack intrinsic motivation to change. The parents that tried taking their child to a health professional, reported a lack of clinical expertise among lifestyle experts to level with children with a neurodevelopmental disorder.

What is helpful?
Agency
Both studies found that allowing your kid agency in making choices is critical to create a healthy habit. It is important to limit the choices, otherwise your child will drown in options. Offer, for instance, a healthy snack and an unhealthy snack and let your child decide whether he/she wants the healthy snack now, or later.

Family engagement
Work as a team! This was a helpful strategy that was reported by most parents in the TRACE study. If you follow the diet with the whole family, the child does not feel left out or punished. Also, just not having snacks at home prevents your child from sneaking into the cabinet and taking one.

Positive reinforcement
It is important to define a goal together with your child. What are we working for? And for how long? You can help your child visualize this goal by making a calendar. Will your child only be rewarded at the end of the goal? Or are there also smaller sub-goals? For some children, a long-term goal such as “sleeping better” or “less belly pains” will be rewarding enough, but other children might need short-term goals.

The role of pets
In the Boston study, almost one-third of the parents reported that they used the role of pets to promote healthy habits. Animals can be used as a positive reinforcement for good choices, but they can also help to maintain healthy routines such as physical activity (walking the dog) and family engagement (walking the dog with the whole family).

 

REFERENCES

  1. Bowling, A. Blaine, R.E., Kaur, R., Davison, K.R. (2019). Shaping healthy habits in children with neurodevelopmental and mental health disorders: parent perceptions of barriers, facilitators and promising strategies. International Journal of Behavioral Nutrition and Physical Activity. 16:52.
  2. TRACE-study. For more information visit project-trace.nl
Please share and like us:
error

This week, my lab at the University of Canterbury published the first investigation1 into whether a mineral-vitamin supplement could change the bacteria in the microbiome of children with ADHD. Our preliminary data, based on our sample of 17 kids (half of whom were given micronutrients and half were given placebo for 10 weeks), hints at increased diversity and changes in the types of bacteria contained in the microbiome of the children exposed to the micronutrients. This type of study starts to moves us beyond the efforts to show that micronutrients benefit some people with psychiatric symptoms, and towards figuring out why they might exert their influence. So what does this mean?

First off, what is the microbiome?

The gut microbiome is defined as the trillions of microbes that inhabit the human digestive tract. In additional to playing a crucial role in digesting food, they also play pivotal roles in immune and metabolic functioning, gene expression, as well as playing a role in the expression of psychiatric symptoms through the gut-brain connection.2 We also know that they generate essential vitamins. When our microbiome gets into a state of dysbiosis (microbial imbalance), in addition to the physical symptoms like reflux, poor digestion, pain, constipation and/or diarrhoea, it is thought that dysbiosis can also lead to increased permeability of the gut wall, increased production of endotoxins, increased inflammation and decreased nutrient synthesis.

How do we learn about what bacteria are within and on us?

Research on the human microbiome has grown exponentially in the past decade. However, it was only recently that we could fairly cheaply quantify and describe the bugs contained within us. 16S rRNA sequencing (the technology we used) is a key methodology in identifying bacterial populations and allows scientists to easily and reliably characterize complex bacterial communities.3 This methodology is a simple and effective alternative to microbial culture, and provides detailed information about the various species of bacteria that are contained within our microbiome. The sequencing gives information on bacterial diversity, as well as details about the specific family (e.g., Bifidobacteriaceae), genus (e.g., Bifidobacterium), and species (e.g., Bifidobacterium Longom).

What about the microbiome of kids with ADHD?

What scientists are now wondering is whether people who suffer from specific psychiatric symptoms, like those associated with ADHD, have a different bacterial composition than those who don’t have these symptoms and whether these differences can help us understand the severity of the symptoms. In other words, is it possible that our bugs can make us impulsive? And if so, if we changed the bugs, can we become less impulsive?

There isn’t a huge literature exploring this topic in ADHD. Preliminary studies suggest that antibiotics in the first 6 months of life may increase risk of ADHD symptoms at 11 years of age,4 although this finding hasn’t been replicated.5 Another study found that the Phylum Actinobacteria is overrepresented in ADHD compared with controls.6 Other research suggests that reduced alpha diversity may exist in young patients with ADHD, specifically that boys with ADHD had more Bacteroidaceae relative to controls, with the species Neisseriaceae identified as a particularly promising ADHD-associated candidate.7 Although this finding of reduced alpha diversity was not observed in treatment-naïve children with ADHD, Jiang and colleagues noted that the more an individual had the species Faecalibacterium, the lower their ADHD severity.8

Overall, there are intriguing signals but the signals are not always replicating. Much more research with larger samples is needed to try to determine if there are reliable bacterial biomarkers. We also need to parse out the effect of diet, medications, age, ethnicity and gender on the results that have been reported. Further, we don’t know whether these differences are causal or a result of ADHD or completely irrelevant to the expression of the symptoms.

We still don’t know if changing the relative amount of a bacteria can change psychiatric symptoms. We know that diet manipulation can change levels of bacteria but whether those changes in bacteria are necessary for improvement in psychological states requires much more research.

So what did we find?

Looking at the microbiome over a short period of time with a small sample is challenging. There is such diversity in the bacteria within us and between us that it is a challenge to explore changes and also whether changes are meaningful. But we did observe some intriguing effects:

  1. The observed taxonomic units (OTU), a measure of community richness, significantly increased in treatment group but not in placebo group. We think this is a good thing.
  2. We observed significant greater decrease in abundance of genus Bifidobacterium from phylum Actinobacteria in active versus placebo and that the more it decreased, the more the ADHD symptom scores dropped. If Bifodobacterium is contributing to the symptoms of ADHD, this is a good thing.
  3. We also observed a significant positive correlation between Actinobacterium abundance and Clinician ADHD IV-RS rating scale before the intervention was introduced, which suggests that Actinobacterium may play a role in the expression of ADHD.

What does this mean?

The small sample makes it difficult to generalize from this study. However, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome. Previous research from our lab has shown that micronutrients do exert some positive effects on ADHD and associated symptoms.9 10 These findings suggest that micronutrient treatment may result in a more diverse microbiome which may in turn, have a positive effect on brain health.

What next?

The field of the microbiome is literally exploding with new studies out every day. The focus currently is trying to find ways to manipulate the microbiome for positive response. This has mainly been explored through either adding in bacteria (in the form of probiotics or psychobiotics if targeting psychological symptoms), diet manipulation, or more recently, fecal microbiota transplants. I do worry a bit that this search for the magic-bullet bacteria that causes distress may turn out to be as disappointing as the search was for candidate genes, but it is worth some effort to figure out if this is an important lead.

Eat2BeNice (New Brain Nutrition) plans to explore the role of the microbiome in multiple ways, including determining whether individuals with high impulsivity/compulsivity have a unique microbiome profile, whether targeted probiotics can improve impulsivity/compulsivity symptoms, and also whether improvement in impulsivity/compulsivity symptoms from diet manipulation and via the use of supplements can be explained via changes in the microbiome. Watch this space!

REFERENCES 

  1. Stevens AJ, Purcell RV, Darling KA, et al. Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder. Sci Rep 2019;9(1):10128.
  2. Frye RE, Slattery J, MacFabe DF, et al. Approaches to studying and manipulating the enteric microbiome to improve autism symptoms. Microb Ecol Health Dis 2015;26:26878-78.
  3. Ames NJ, Ranucci A, Moriyama B, et al. The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science. Nurs Res 2017;66(2):184-97.
  4. Slykerman RF, Coomarasamy C, Wickens K, et al. Exposure to antibiotics in the first 24 months of life and neurocognitive outcomes at 11 years of age. Psychopharmacology (Berl) 2019;236(5):1573-82.
  5. Axelsson PB, Clausen TD, Petersen AH, et al. Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder. J Child Psychol Psychiatry 2019;60(2):151-59.
  6. Aarts E, Ederveen THA, Naaijen J, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One 2017;12(9):e0183509.
  7. Prehn-Kristensen A, Zimmermann A, Tittmann L, et al. Reduced microbiome alpha diversity in young patients with ADHD. PLoS One 2018;13(7):e0200728.
  8. Jiang HY, Zhou YY, Zhou GL, et al. Gut microbiota profiles in treatment-naive children with attention deficit hyperactivity disorder. Behav Brain Res 2018;347:408-13.
  9. Rucklidge JJ, Eggleston MJF, Johnstone JM, et al. Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial. J Child Psychol Psychiatry 2018;59(3):232-46.
  10. Rucklidge JJ, Frampton CM, Gorman B, et al. Vitmain-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised palcebo-controlled trial. The British Journal of Psychiatry 2014;204:306-15.
Please share and like us:
error

Feeling more happy after a run? Or feeling a bit blue during the dark winter days? Regular exercising and regular daylight exposure can influence your mood, behaviour and sleep-wake cycle 1,2,3. But can this also be used in a therapeutical setting, for instance in addition to or instead of the usual treatment with medication?

The PROUD trial aims to investigate the potential of bright light therapy and physical exercise to improve and prevent depression and obesity in adolescents and young adults with ADHD. This clinical trial is part of the CoCA research project, in which comorbid conditions of ADHD are investigated [insert hyperlink: https://coca-project.eu/coca-phase-iia-trial/study/]. In addition, we collect the stool samples of all participants in order to investigate the effects of physical exercise on the gut microbiome and how this is linked to behaviour. That part of the study is part of the Eat2beNICE research project.

Most people with Attention Deficit Hyperactivity Disorder (ADHD) receive medication to reduce their symptoms4. While this medication works well for many people, there is a lot of interest in other types of treatment. One reason for this is that people with ADHD suffer from additional conditions, such as depression5 and obesity6. The risk for developing these comorbid conditions is especially high during adolescence and young adulthood4.

Adolescents and young adults (age 14-45) with ADHD that want to participate are randomly assigned to one of three groups: 10-weeks of daily light therapy (30 minutes), 10-weeks of daily physical exercise (3x per day) or 10-week care as usual (for instance, the normal medication). The random assignment is very important here in order to compare the different interventions. We don’t want to have all people that like sports in the physical exercise group, because then we don’t know if the effects of the physical exercise are due to the intervention, or due to the fact that these people just like sports better.

Another nice feature of the study is that it uses a phone app (called m-Health). This app is used to remind the participants to do their exercise or light therapy, but it also gives feedback and summaries of how the participant is doing. The app is linked to a wrist sensor that measures activity and light.

The clinical trial is currently ongoing in London (England), Nijmegen (Netherlands), Frankfurt (Germany) and Barcelona (Spain). We can’t look at the results until the end of the trial, so for those we will need to wait until 2021. But in the mean time the PROUD-researchers have interviewed four participants. You can read these interviews here:

This blog is based on the blog “10 weeks of physical exercise or light therapy: what’s it like to participate in our clinical trial?” by Jutta Mayer and Adam Pawley, 9 Oct. 2018 on MiND the Gap – https://mind-the-gap.live/2018/10/09/10-weeks-of-physical-exercise-or-light-therapy/

REFERENCES

  1. Terman, M. Evolving applications of light therapy. Sleep Medicine Reviews. 2007; 11(6): 497-507.
  2. Stanton, R. & Reaburn, P. Exercise and the treatment of depression: A review of the exercise program variables. Journal of Science and Medicine in Sport. 2014; 17(2):177-182
  3. Youngstedt, S.D. Effects of exercise on sleep. Clinical Sports Medicine. 2005; 24(2):355-365.
  4. Cortese 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.
  5. Jacob 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.
  6. 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.
  7. Meinzer 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
Please share and like us:
error

MoBa is short for The Norwegian Mother and Child Cohort Study which is a large pregnancy observational study. During the years 1999-2008 pregnant women in Norway were recruited to the study. The study is conducted by the Norwegian Institute of Public Health. Questionnaires regarding health, diet and environment were sent out to the women during and after pregnancy. Women are sent regular follow-up questionnaires. As the child grows up, the child also completes questionnaires. In addition, the fathers were invited to participate with a questionnaire when their partner was pregnant. Biological samples were also collected from the mother, father and child. Today there are 114 500 children, 95 000 mothers and 75 000 fathers participating in the study.

https://www.fhi.no/en/studies/moba/

The study was set up to gain knowledge about the causes behind serious disease. The study is unique because it gathers information from fetal (in vitro) life and follows the offspring into adulthood. In this manner it is possible to look at early influences and later disease. The study is prospective, which means that information about mothers, fathers and their offspring is registered before a disease has manifested itself. With this design, women are asked questions several times during her pregnancy and do not have to try to remember what she did when looking back at her pregnancy.

MoBa is population-based and became nationwide with 50 participating hospitals in Norway. For more information on the many publications based on MoBa data, visit this link:

https://www.fhi.no/en/studies/moba/for-forskere-artikler/publications/

The participating women in MoBa also filled in a questionnaire about eating habits before and during pregnancy.

.

Please share and like us:
error

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

 

Please share and like us:
error

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

Please share and like us:
error

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

Please share and like us:
error


Welcome to New Brain Nutrition. You can enjoy FREE Online Courses when you Log In or Join here.

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.

Partners:
You may log in here to our Intranet website with your authorized user name and password.