I have noticed a growing number of companies offering to measure nutrient levels and then offering a personalized treatment approach to address deficiencies identified. I have also been sent individual blood results from members of the public and asked whether the results can be used to direct the best treatment. Others contact me and tell me their nutrient levels are “normal” so their doctor told them there was no need for additional nutrients.

It is a reasonable question because there are many studies that suggest that people with psychological problems such as ADHD have lower levels of nutrients in their blood relative to the nonclinical population. What we don’t know is whether it is necessary to be deficient in order to benefit from additional nutrients than what you can get out of your diet.

So what does the research say?

Our lab at the University of Canterbury in New Zealand is one of a few that has specifically investigated whether nutrient levels are predictive of response to a broad spectrum micronutrient intervention. It is important to note that not many labs take this approach, that is giving a combination of nutrients together and then assess treatment response. Many researchers make the assumption that one must be deficient to benefit from nutrients, and therefore select people for the deficiency and only treat them. We treat everyone, regardless of identified deficiency, and then assess whether the deficiency predicts who will respond and who won’t.

Overall, our research shows that the effect, if there is one, is weak, and certainly not useful at an individual level as a good predictor of treatment outcome.

Here is what we did: We assessed some key nutrients pre-treatment via serum/plasma. We measured vitamin B12, vitamin D, zinc, copper, folate, ferritin, potassium, sodium, calcium, and homocysteine. We have looked at two data sets – an adult study and a child study, both comparing vitamins/minerals to placebo in the treatment of symptoms associated with ADHD.

Findings from the adult ADHD trial:

Participants improved significantly on all outcome measures after exposure to the micronutrients for 8 weeks; 61% were identified as responders.

But, there was no relationship between baseline functioning and baseline nutrient levels. This was a bit surprising given that studies have identified deficiencies in magnesium, zinc and iron in children with ADHD. Surprisingly, we didn’t find that these nutrient levels were highly correlated with ADHD symptoms.

Very few predictors were identified. We found that greater pre-treatment with ferritin predicted who would be an ADHD responder. We wondered if those with higher ferritin had higher inflammation and therefore responded more rapidly to the treatment as the micronutrients may have improved inflammation.

Lower pre-treatment vitamin D predicted greater change on a measure of mood. This finding is not unexpected as low vitamin D levels have been associated with low mood. Pre-treatment copper gave us a signal, but it was weak and mixed.

Micronutrient supplementsIt is important to note that while there were these small signals, there were still many people with normal levels of these nutrients who benefitted from the nutrient approach, only there were fewer relative to those with vitamin D and copper deficiencies.

No other relationships between baseline nutrient levels and treatment response were identified. In other words, zinc, iron and vitamin B12 pre-treatment did not predict who would benefit and who would not. Further, there were no specific demographic variables (age, socio-economic status, gender, marital status, education) which contraindicated micronutrient treatment for ADHD in adults.

Findings from the child trial:

We identified that 49% of the children responded to the micronutrient intervention. Substantial nutrient deficiencies pre-treatment were observed only for vitamin D (13%) and copper (15%), otherwise most children entered the trial with nutrient levels falling within expected ranges. Lower pre-treatment folate and B12 levels, being female, greater severity of symptoms and co-occurring disorders pre-treatment, more pregnancy complications and fewer birth problems were identified as possible predictors of greater improvement for some but not all outcome measures although predictive values of all of them were weak. Lower IQ and higher BMI predicted greater improvement in aggression.

It is important to note that levels of folate pre-treatment for ADHD responders was within the normal reference range for folate (>8nmol/L). In other words, the blood tests did not identify responders as deficient in folate, just lower relative to non-responders. Note though, that there were many children with higher B12 and folate who did benefit from the nutrient treatment. No other relationships between pre-treatment nutrient levels and treatment response were identified.

It is also important to point out that across two studies, replication did not occur and any findings we did observe were incredibly modest. As such, they could not be used at an individual level to reliably identify who might benefit from this treatment approach. We see this as good news as it means people don’t have to feel they need to get expensive testing done before trying nutrients. The bad news is that the search is still on to figure out why some people respond and some don’t.

Although not reported in these trials, we have also looked at the predictive value of nutrient levels recorded from hair samples and similarly, the levels were also not overly helpful at predicting treatment response.

Do nutrient levels have to change for benefit to occur?

Now this is a tricky question. But we have now published a study looking at this very question, that is, whether change in a nutrient biomarker is correlated with improvement in mental health. Our overall findings were that they were not.

I think this type of question stems from research in medicine such as physicians tracking cholesterol levels in order to determine whether they are associated with the progression of disease (such as incidence of stroke). Change in cholesterol levels are used to estimate risk for future cardiovascular events.

In the mental health world, at best, they are weakly correlated with improvement in symptoms and probably not that helpful. We investigated whether changes in serum nutrient levels mediate clinical response to a micronutrient intervention for ADHD. Data were compiled from two ADHD trials (8-10 weeks), one in adults (n = 53) and one in children (n = 38). Seven outcomes included change in ADHD symptoms, mood, overall functioning (all clinician-rated) as well as response status. Change in serum/plasma nutrient levels (vitamins B12 and D, folate, ferritin, iron, zinc, and copper) were considered putative mediators.

We found that a decrease in ferritin and an increase in copper were weakly associated with greater likelihood of being identified as an ADHD responder; none of the other nutrient biomarkers served as mediators. Perhaps we need to look to see if other tissue (like hair or microbiome samples) might be more useful. Monitoring these biomarkers is unlikely helpful in understanding clinical response to a broad-spectrum micronutrient approach.

Blood levels don’t necessarily tell us what is going on in the brain and what nutrients are being used and what isn’t being used. We didn’t look at ALL nutrients so it may be we missed an important biomarker. It may be ratios are more important. But next time a professional is keen to track nutrient levels as a proxy for response, perhaps be a bit sceptical about whether the data support such testing.

Is the term deficiency accurate?

The term “deficiency”, as is often used in the ADHD literature when discussing nutrient levels, may be problematic. Although research shows that the ADHD group mean nutrient levels are often below control group means, the ADHD means are typically still falling within the normal reference range, potentially challenging the use of the term “nutrient deficiency” when attempting to investigate causes of ADHD and in relation to predicting response to nutrients. Given that reference ranges are generally defined as the set of values that 95 percent of the normal population falls within, this does not necessarily mean that these ranges are best equipped to identify what is required for optimal health for any particular individual.

Had functional ranges (the range used to assess risk for disease before the disease develops) been used in these studies, many more would have been identified with “deficiencies”. An important hypothesis which requires further investigation is that some individuals may have suboptimal nutrition for brain health despite having nutrient levels within the reference range. In other words, they might have a nutrient deficiency relative to their metabolic needs rather than relative to general population levels.

It is exciting that the EAT2BeNice consortium (NewBrainNutrition) will be looking at nutrient levels alongside other biomarkers so we can confirm whether these results are replicable. Hopefully some of the other biomarkers will prove more useful at predicting treatment response. Afterall, it is a valid clinical question to wonder – when a treatment works, who does it work for and why? These types of data inform clinical practice and can help the consumer decide whether you should go for that expensive testing, or not bother. At this stage, I wouldn’t bother.

References

  1. Rucklidge JJ, Johnstone JM, Gorman B, Boggis A, Frampton CM. Moderators of treatment response in adults with ADHD treated with a vitamin-mineral supplement. Prog Neuropsychopharmacol Biol Psychiatry. 2014;50:163-71.
  2. Rucklidge JJ, Eggleston MJF, Darling K, Stevens A, Kennedy M, Frampton CM. Can we predict treatment response in children with ADHD to a vitamin-mineral supplement? An investigation into pre-treatment nutrient serum levels, MTHFR status, clinical correlates and demographic variables. Prog Neuropsychopharmacol Biol Psychiatry. 2018.
  3. Rucklidge JJ, Eggleston MJF, Boggis A, Darling K, et al. Do Changes in Blood Nutrient Levels Mediate Treatment Response in Children and Adults With ADHD Consuming a Vitamin–Mineral Supplement? Journal of Attention Disorders. 2019. 0:1087054719886363.

 

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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 clinical trial? 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
The TRACE Study, New Brain Nutrition

 

 

 

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 a 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 YouTube video explains the assessments described above, in Dutch: ADHD en voeding: TRACE-onderzoek testdag

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Children with ADHD who keep taking micronutrients over one year are mostly in remission in their symptoms with no side effects

The results from a University of Canterbury (UC) study into the longer term effects of micronutrients on ADHD symptoms in children was recently published in the Journal of Child and Adolescent Psychopharmacology.  

This study was led by Dr Kathryn Darling at the Mental Health and Nutrition Lab in Christchurch (under the supervision of Eat2BeNice Scientist Julia Rucklidge) and looked at the long-term effects of a broad-spectrum micronutrient (vitamins and minerals) in attention-deficit/hyperactivity disorder (ADHD) treatment.

Eighty-four of the 93 children who entered a 10-week randomised controlled trial (micronutrients versus placebo), followed by a 10 week phase of all children taking micronutrients, then completed follow-up assessments after 12 months. This allowed us to gather valuable information about what happens when people choose to stay on or come off the micronutrient treatment.

The study showed that children who benefit in the short term from taking a broad-spectrum vitamin/mineral formula maintain those benefits or continue to improve when they keep taking it longer term, without side effects.

Continued micronutrient treatment was associated with improvements in ADHD symptoms which were similar to, or greater than, those associated with stimulant medication. Unlike stimulant medications, micronutrients were associated with improvements, rather than worsening, in mood and anxiety. This indicates that micronutrients can be a serious treatment option for those who choose not to take medications. Micronutrients may be especially helpful for children with ADHD who also have difficulties with mood or anxiety.

Other key findings from this research:

  • Those who continued to take micronutrients did not have any ongoing side effects.
  • Children who continued to take micronutrients and children who changed to medications (like methylphenidate/Ritalin/Concerta) either stayed well or continued to show improvement in ADHD symptoms at 12-month follow-up assessment, while those who stopped treatment altogether did not.
  • Children who switched from micronutrients to medications like methylphenidate/Ritalin were more likely to have problems with mood or anxiety at the 12-month follow-up assessment, which were worse than at the end of the micronutrient trial. After the end of the trial, mood and anxiety symptoms had generally continued to improve for the children who stayed on micronutrients, and mostly stayed the same for those who stopped treatment.
  • The most common reasons people stopped taking micronutrients were the cost and number of pills to swallow.
  • Based on dominant treatment, more of those who stayed on trial micronutrients (84%) were identified as “Much” or “Very Much” improved overall relative to baseline functioning, compared to 50% of those who switched to psychiatric medications and only 21% of those who discontinued treatment. Fifteen (79%) of those still taking micronutrients, 8 (42%) of those using medications, and 7 (23%) of those who discontinued treatment were considered in remission based on parent-reported ADHD. Those who stayed on micronutrients were more likely to have failed medication treatment in the past.

It is important to note that these findings are reporting on group averages, so the effect of micronutrients or other treatments for any specific child may have been different. People do respond differently to any form of treatment – perhaps they benefited across all areas of functioning or perhaps had no benefit at all.

This study is limited due to its naturalistic observational status but allows us to evaluate effectiveness in the real world. No funds were received from the manufacturer of the micronutrients.

If you want to know more about the micronutrients we studied, email mentalhealthnutrition@canterbury.ac.nz

 

Reference:

Darling, K. A., Eggleston, M. J., Retallick-Brown, H., & Rucklidge, J. J. (2019). Mineral-Vitamin Treatment Associated with Remission in Attention-Deficit/Hyperactivity Disorder Symptoms and Related Problems: 1-Year Naturalistic Outcomes of a 10-Week Randomized Placebo-Controlled Trial. Journal of child and adolescent psychopharmacology.

https://doi.org/10.1089/cap.2019.0036

 

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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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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.

 

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To investigate whether nutrition plays a role in inhibitory control and executive functioning early in life, we collected data on behavior using different tasks (see previous blog). To perform these tasks, we choose to visit the children at home with the aim 1) to burden the families less, and 2) to test the children in their home environments where they are probably more at ease. Testing 3-year-old children is very fun a

October 1

nd can also be challenging at the same time. I will share some anecdotes and experiences of my data collection as inspiration for others testing young children.

Attention
Some tasks had lengthy instructions and required the child to perform several practice trials, resulting in the child losing his/her attention. The sequence of the tasks was constructed in such a way that the child’s attention was maintained as long as possible. For example, the tasks that required more attention, focus and instructions were performed first.

Sometimes children said to be not in the mood to play anymore, or that they didn’t know what to do despite passing the practice trials. Repeating the rules is not possible, because it means that some children will receive more instructions than other children. I solved this problem by telling the child that he/she would be rewarded if he/she finished the task. Rewards could be a fun game they can play next, or some snacks that the parents agreed to giving.

Parents
Parents sometimes tended to help their child. To prevent this, it is very important to instruct the parents not to help their child. Another way to prevent the parent from helping is to keep them busy by having them fill in a questionnaire, or to turn to the child and say things like: “are you a bit nervous because Mum is looking?” Sentences as these work very well, as you are not telling the parent directly what to do, but they understand the hint immediately.

Siblings
Toddlers often have siblings; sometimes younger siblings and sometimes older siblings. If possible, parents are asked to arrange the situation this way that the siblings are not at home and/or are asleep. When not possible, an assistant accompanying the experimenter can take care of the siblings, for example by taking the sibling outside and play soccer in the neighborhood. Everything for science!

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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.
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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
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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.
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Behavior results from the complex interplay between genes and environment. Our genes predispose us to how we act and feel, by influencing how our brain develops and functions. This way, certain genetic variants in our genome increase the risk of developing mental health problems (while others may decrease this risk). Whether someone actually develops a mental health disorder or not, depends on many other factors in our environment, such as stressors and experiences. Nonetheless, studying these genetic risk factors for mental health conditions is an important aspect of understanding these disorders.

As an example of such research, we have now identified several genetic risk factors that contribute to cocaine dependence. For this we combined genetic data from a lot of studies, including more than 6000 individuals. What’s even more interesting is that we found that the genetic variants that are related to cocaine dependence are correlated with the genetic risk factors for other conditions such as ADHD, schizophrenia and major depression. What this means is that certain small variations in DNA increase the risk for not just cocaine dependence, but actually several psychiatric conditions. Probably, there is a common biological mechanism that underlies all these conditions. Thanks to our genetic research, we are now only a small step closer towards unraveling these mechanisms.

We also wrote a blog post explaining our research findings. You can read it here: https://mind-the-gap.live/2019/07/04/cocaine-dependence-is-in-part-genetic-and-it-shares-genetic-risk-factors-with-other-psychiatric-conditions-and-personality-traits/

The original publication can be found here: https://www.sciencedirect.com/science/article/pii/S0278584619301101?via%3Dihub

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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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