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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Have you experienced drowsiness after eating a large meal? Has an important presentation made your stomach turn? Seeing a special someone made you feel butterflies in your stomach? If you have (and you most likely have), then you know how strong the connection between the brain and the gut is.

Scientists have found that many chronic metabolic diseases, type 2 diabetes, mood disorders and even neurological diseases, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders (1). The importance of the association between the gut and the brain is gaining momentum with each new study. However, the way HOW the signaling between these two integral parts of the body exactly works hasn’t been clear until recently.

It was thought for a long time that the only “communication channel” between the gut and the brain was the passive release of hormones stimulated by the consumed nutrients. Hormones entered the bloodstream and slowly notified the brain that the stomach is full of nutrients and calories. This rather slow and indirect way of passing messages takes from minutes to hours.

But now, a recent study (2) has elegantly proven that the gut can message the brain in seconds! Using a rabies virus enhanced with green fluorescence, the scientists traced a signal as it traveled from the intestines to the brainstem of mice, crossing from cell to cell in under 100 milliseconds – faster than the blink of an eye.

The researchers had also noticed that the sensory cells lining the gut were quite similar to the receptors in the nose and on the tongue (3). The effects, however, differ. In the mouth, the taste of fatty acids triggers signals to increase hunger, whereas in the small intestine, fatty acids trigger signals of satiety. This means that the discovered “gut feeling” might be considered as a sixth sense, a way of how the brain is being signaled when the stomach is full.

This new knowledge will help to understand the mechanism of appetite, develop new and more effective appetite suppressants and help those struggling with weight and problematic eating patterns.

REFERENCES
(1) Pellegrini C et al (2018) Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases? Acta Neuropathol 136:345. doi:10.1007/s00401-018-1856-5

(2) Kaelberer et al (2018) A gut-brain neural circuit for nutrient sensory transduction. Science 361(6408):eaat5236. doi:10.1126/science.aat5236

(3) Bohórquez and Liddle (2015) The gut connectome: making sense of what you eat. J Clin Invest 125(3):888–890. doi:10.1172/JCI81121

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Psychobiotics are helpful bacteria (probiotics) or support for these bacteria (prebiotics) that influence the relationship between bacteria and brain. The human digestive system houses around 100 trillion of these bacteria, outnumbering the human body cells 10:1. Probiotics provide a great deal of functions vital to our well-being, like supporting the digestion process and improving the absorption of nutrients. Based on the latest research, helpful gut bacteria that can also positively affect the brain – psychobiotics – benefit people suffering from chronic stress, poor mood, or anxiety-like symptoms (1).

There are 3 ways psychobiotics can affect your mental health:

  • Brain chemicals like serotonin, dopamine, and noradrenaline can be produced in the intestines directly by gut microbiota.
  • Battling with and protecting from stress by modifying the level of stress hormones.
  • When an inflammation occurs, inflammatory agents are elevated throughout the body and brain and can cause depression and other mood and cognitive disorders. Psychobiotics can affect the brain by lowering inflammation.

Lactobacillus and Bifidobacterium are the most popular probiotics with respect to mental health (1).

Disruption of the balance of gut bacteria is quite common due to the use of different kinds of medications, antibiotics, artificial preservatives, poor food and water quality, herbicides, stress, and infections (2, 3, 4).

In order to support a healthy microbiota, one should start from eating a diverse range of foods rich in different plant sources. Foods that contain lots of fiber or are fermented also promote the growth of beneficial gut bacteria. Excessive consumption of sugar and artificial sweeteners should be minimized. Managing stress levels, exercising on a regular basis, not smoking and getting enough sleep are also important for keeping microbiota in good condition. When taking antibiotics, one should make sure to consume probiotics so the body can maintain the bacteria it needs to stay healthy.

For people needing help regarding mental health problems, psychobiotics may be a promising relief. Psychobiotics are well-adapted to the intestinal environment and naturally modulate gut–brain axis communications, thereby reducing the chance of adverse reactions.

It is possible that even simple prescribing of a particular diet may be sufficient to promote the selective proliferation of natural or therapeutically introduced psychobiotics (5). Further research focusing on the strain and dosage of psychobiotics, duration of treatment, and the nature of mental disorders will help to determine the most efficient ways of helping people to improve their mental health.

REFERENCES
Abhari A, Hosseini H (2018) Psychobiotics: Next generation treatment for mental disorders? J Clin Nutr Diet. 4:1. doi:10.4172/2472-1921.100063

Carding et al (2015) Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 26: 10.3402/mehd.v26.26191

Lozano et al (2018) Sex-dependent impact of Roundup on the rat gut microbiome. Toxicol Rep. 5:96–107. doi: 10.1016/j.toxrep.2017.12.005

Paula Neto et al (2017) Effects of food additives on immune cells as contributors to body weight gain and immune-mediated metabolic dysregulation. Front Immunol. 8:1478. doi:10.3389/fimmu.2017.01478

Kali (2016) Psychobiotics: An emerging probiotic in psychiatric practice. Biomed J. 39(3):223-224. doi:10.1016/j.bj.2015.11.004

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A hot topic these days, that one can hear more and more information about is the microbiota-gut-brain axis, the bidirectional interaction between the intestinal microbiota and the central nervous system nowadays, this has become a hot topic. We are becoming increasingly aware that gut microbiota play a significant role in modulating brain functions, behavior and brain development. Pre- and probiotics can influence the microbiota composition, so the question arises, can we have an impact on our mental health by controlling nutrition and using probiotics?

Burokas and colleagues aimed to investigate this possibility in their study (2017), where the goal was to test whether chronic prebiotic treatment in mice modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior.

In the first part of the study, the researchers fed mice with prebiotics for 10 weeks. They were administered the prebiotics fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), a combination of both, or water. FOS and GOS are soluble fibers that are associated with the stimulation of beneficial bacteria such as bifidobacterium and lactobacillus.

Behavioral testing started from the third week including

  • the open field test (anxiety – amount of exploratory behavior in a new place),
  • novel object test (memory and learning – exploration time of a novel object in a familiar context), and
  • forced swimming test (depression-like behavior – amount of activity in the cylinder filled water).

Meanwhile, plasma corticosterone, gut microbiota composition, and cecal short-chain fatty acids were measured. Taken together, the authors found that the prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic (anti-anxiety) effects. However, there were no major effects observed on cognition, nociception (response to pain stimulus), and sociability; with the exception of blunted aggressive behavior and more prosocial approaches.

In the second part, FOS+GOS or water-treated mice were exposed to chronic psychosocial stress. Behavior, immune, and microbiota parameters were assessed. Under stress, the microbiota composition of water-treated mice changed (decreased concentration of bifidobacterium and lactobacillus), which effect was reversed by treatment with prebiotics.

Furthermore, it was found that three weeks of chronic social stress significantly reduced social interaction, and increased stress indicators (basal corticosterone levels and stress-induced hyperthermia), whereas prebiotic administration protected from these effects.

After stimulation with a T-cell activator lectin (concanavalin A), the stressed, water-treated mice group presented increased levels of inflammatory cytokines (interleukin 6, tumor necrosis factor alpha), whereas in animals with prebiotics had these at normal levels.

Overall, these results suggest a beneficial role of prebiotic treatment in mice for stress-related behaviors and supporting the theory that modifying the intestinal microbiota via prebiotics represents a promising potential for supplement therapy in psychiatric disorders.

Watch YouTube Video:
https://youtu.be/E479yto8pyk

REFERENCES
Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017). Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice. Biological Psychiatry, 82(7), 472–487. https://doi.org/10.1016/j.biopsych.2016.12.031

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Shine a Light on ADHD

October is international ADHD Awareness month. Young researchers of the MiND research project and 4QuarterFilms just published this short documentary that shines a light on living with ADHD, from a personal and a scientific perspective.

Watch the video here: http://newbrainnutrition.com/adhd-shine-a-light/

We thank the following professionals who were interviewed in this video:
Dr. Barbara Franke and Dr. Corina Greven, of Donders Institute, Radboud University Medical Center
Dr. Philip Asherson, Dr. Eric Taylor, and Dr. Kai Syng Tan of King’s College London
Mrs. Andrea Bilbao of ADDISS, ADHD Europe
We also thank ms. Evie Travers, mr. Bryn Travers and mr. Aziz who were interviewed in this video.

Shine_a_Light_on_ADHDThe film was made possible with the help of the EU-funded programs:
MiND (EU horizon 2020 program no 643051) http://mind-project.eu/
Aggressotype (EU FP7 program No 602805) http://www.aggressotype.eu/
CoCA (EU horizon 2020 program No 667302) http://coca-project.eu/
Eat2beNICE (EU horizon 2020 program No 728018). http://newbrainnutrition.com/

 

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A team of Iranian researchers recently published a meta-analysis seeking to determine what, if any, association there may be between low Vitamin D levels and ADHD in children and adolescents.

Combining the results from thirteen studies with 10,334 participants, they found that youth with ADHD had “modest but significant” lower serum concentrations of 25-hydroxyvitamin D than normally developing children. The weighted mean difference was just under 7 nanograms per milliliter. The odds of obtaining such a result by chance would be less than one in a thousand (p < .001). There was little to no sign of publication bias. Between-study heterogeneity, however, was very high (I2 = 94).

Vitamin D and ADHDThese results suggest an association. But are low serum levels of Vitamin D a cause or effect of ADHD? Causation is vastly more difficult to establish than association. To begin to tease this out, the researchers identified four prospective studies that compared maternal Vitamin D levels with the subsequent development of ADHD symptoms in their children. Two of these used maternal serum levels, and two used umbilical cord serum levels. Together, these studies found that low maternal Vitamin D levels were associated with a 40% higher risk of ADHD in their children. Whether maternal serum or umbilical cord serum measurements were used had little or no effect on the outcome. Study heterogeneity was negligible. But the authors noted that this result “should be considered with caution” because it was heavily dependent on one of the prospective studies included in the analysis. All of which suggests a need for further prospective studies.

In the meantime, the authors suggest it would be prudent to increase sun exposure and Vitamin D supplementation given the prevalence of Vitamin D deficiency.

REFERENCES

Yadollah Khoshbakht, Reza Bidaki, and Amin Salehi-Abargouei, “Vitamin D Status and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Observational Studies,” Advances in Nutrition, vol. 9, issue 1, p. 9-20 (2018).

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Mediterranean diet could prevent depression, new study finds” [CNN]; “Mediterranean diet ‘may help prevent depression‘” [BBC]. The publication of Lassale and her colleagues in the prestigious scientific journal Molecular Psychiatry on the association between Mediterranean Diet and depression, received a lot of attention in the media last week.

So, can diet really influence your mental health? The publication of Lassale shows that there are indications that what you eat is related to how you feel. But because this study is an observational study, we can’t conclude anything yet about causation. In other words, we don’t know yet whether eating healthy causes you to feel less depressed, or whether feeling depressed causes you to eat unhealthy.

Causal links between diet and mental health

Diet and mental healthThe researchers of the European consortium Eat2beNICE are investigating exactly this causal link. The way we do this is through clinical trials. In this way, we first let chance decide whether a person receives a particular diet or is part of the control group. Through this randomization we can be sure that the differences that we find between the two groups are really due to the dietary intervention that people received, because all other factors are the same between the two groups.

Specifically for the effects of the Mediterranean diet on behaviour, in the Eat2beNICE project we are using the information and measurements available from the PREDIMED-PLUS trial. In this study, we are looking specifically for the effect of a calorie-restricted Mediterranean diet, combined with physical activity, on several behavioral outcomes related with several psychiatric diseases of adults at high cardiovascular risk.

At the same time, we are conducting three other clinical trials:

  1. In Nijmegen (The Netherlands), we investigate the effects of a very strict, hypo-allergenic diet on behavioural problems in children with ADHD.
  2. We are investigating the effects of vitamin supplements in a clinical trial that will be conducted in Mannheim(Germany) and Groningen(The Netherlands).
  3. Researchers in Barcelona (Spain) and Frankfurt (Germany) are investigating the effects of probiotics (i.e. bacteria that are good for you) on mental health in adults that are highly impulsive and/or aggressive.

Through these studies we hope to be able to identify if these types of food improve mental health and in which circumstances. This can have big implications for psychiatry, where putting someone on a specific, personalised diet may be a way to improve treatment. Also, people who are at a risk for developing mental health problems may benefit from specific diets to reduce this risk. But before this can be put into action, we first need good scientific data on what really works.

How can food drive human behaviour?

A second aim of our large research consortium is to identify the mechanisms between nutrition and the way the brain works. We think that the bacteria that live in your gut play a large role in this, as they interact with other systems in your body, including your brain. So we are collecting poop samples of the people that are participating in our clinical trials to identify which bacteria are more or less common in our participants compared to the control population. We are also measuring our participants’ behaviour and we will scan their brains. We hope that this will help us understanding better why certain types of food can be beneficial for mental health, and why some others increase the risk for mental health problems. This too will help to elucidate, and understand, the causal links between food and behaviour.

In short, we are very thankful for the study of Lassale and her colleagues, for backing up the evidence that what you eat is related to how you feel and behave. Now there’s work for us to do to prove the causal and mechanistic links. We’ll keep you posted here!

 

Authors Jeanette Mostert and Alejandro Arias-Vasquez work at the department of Genetics at the Radboud University Medical Center in Nijmegen, The Netherlands. Alejandro Arias-Vasquez is the project coordinator of the Eat2beNICE project. Jeanette Mostert is the dissemination manager.

 

Further reading

Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2018 Sep 26. doi: 10.1038/s41380-018-0237-8.

 

Blog by Jordi Salas explaining the Lassale paper and the PREDIMED trial:
http://newbrainnutrition.com/category/nutrition/mediterranean-diet/

Blog by Jolanda van der Meer on hypo-allergenic diet (TRACE study): http://newbrainnutrition.com/adhd-and-food-elimination-diet/

Blog by Julia Rucklidge on trials with vitamin supplements: http://newbrainnutrition.com/micronutrients-and-mental-health/

Blog by Judit Cabana on the Gut-Brain axis: http://newbrainnutrition.com/the-gut-brain-axis-how-the-gut-relates-to-psychiatric-disorders/

 

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Constantly feeling low mood and blue, losing of pleasure in life and appetite or having difficulties to have good sleep.

These are just some of the symptoms of one of the most prevalent mental conditions worldwide: depression. It affects hundreds of millions people globally, particularly women. Although depression seems to have a genetic component, lifestyle factors like diet have been suggested to play possible roles in the development of this condition and the degree of their symptoms. In fact, many different studies have suggested that different healthy diets may have important benefits for depression.

did i eat thatIn a recently published meta-analysis at the prestigious scientific journal Molecular Psychiatry, Lassale and coworkers aimed to summarize current epidemiological evidence in relation to healthy dietary patterns and depression. They included a total of 41 high quality observational studies conducted in healthy people from different countries, focusing on several types of well-known healthy dietary indices: Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), and the Dietary Inflammatory Index. These healthy dietary indices score favorably for the consumption of different “healthy” foods, such as fruits and vegetables, nuts, cereals, legumes and healthy fats; and they penalize the consumption of “unhealthy” foods, such as processed foods.

The main findings of the Lassale meta-analysis revealed that those persons following more closely the Mediterranean diet, and those following less the pro-inflammatory diet, showed lower risk of depression and depressive symptoms. Similar beneficial results were observed with a high adherence to the HEI and AHEI diets, yet the evidence was not as strong as with the Mediterranean diet. Indeed, the dietary patterns evaluated in this study contain foods and nutrients which may modulate important biological processes related with depression. For example, healthy diets may reduce oxidative stress and inflammation processes, improve insulin sensitivity and blood circulation in the brain.

These important findings give a strong basis to the role of healthy dietary patterns like the Mediterranean diet in preventing depression and depressive symptoms, and they contribute to build future dietary recommendations to prevent this mental condition.

However, as the authors comment, it is important to keep in mind that all the studies included are observational, meaning, it is not possible to establish causal effects between diet and depression.

To establish causality that can be used to directly translate the knowledge into clinical practice, science needs specific intervention studies. In these studies, a healthy diet is followed for a long time and depression incidence is evaluated.

An example of this is the study conducted in the frame of the PREDIMED study with a population of Mediterranean adults at high cardiovascular risk. In this study, participants consuming the Mediterranean diet supplemented with nuts showed 41% protection against depression, although these benefits were only observed in people with diabetes. In view of the PREDIMED-Plus trial, a multicenter study is being conducted in Spain for the primary prevention of cardiovascular disease using an intensive lifestyle intervention. It will be possible to confirm these results and have new knowledge in the field of depression. With PREDIMED-plus, the investigators will be able to evaluate whether an energy-restricted Mediterranean diet,  with promotion of  physical activity, may be effective for reducing the risk of depression in elders at high cardiovascular risk. In case of the Eat2BeNice study we plan to analyse in the future the effect of PREDIMED-PLUS interventions not only on depression but also on mood and especially on impulsivity and compulsivity, two important domains related to brain function.

Overall, following a healthy diet, like Mediterranean diet, not only has important benefits for different aspects of human health but also it is likely that the diet prevents depression,  depressive-related symptoms and possible other mental related conditions. For this reason, a healthy diet nourishes a healthy mind.

 

References

Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2018 Sep 26. doi: 10.1038/s41380-018-0237-8.

Sánchez-Villegas A, Martínez-González MA, Estruch R, Salas-Salvadó J, Corella  D, Covas MI, Arós F, Romaguera D, Gómez-Gracia E, Lapetra J, Pintó X, Martínez JA, Lamuela-Raventós RM, Ros E, Gea A, Wärnberg J, Serra-Majem L. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med. 2013 Sep  20;11:208. doi: 10.1186/1741-7015-11-208.

 

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In studies about treatment for children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), it is important to use valid and reliable instruments to measure effects. A valid instrument can measure a difference in symptoms before and some time after the treatment has started. Usually questionnaires for parents and teachers are used.

In the TRACE project, currently running in the Netherlands, we are looking at the effectiveness of a dietary intervention versus care as usual, for children diagnosed with ADHD in the age group of 5-12 year old. In addition to the standard questionnaires, there is an observation instrument called the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS). This instrument was added in the TRACE project as an objective measurement for changes in behavior.

DB-DOS, ADHDThe DB-DOS was originally developed to measure disruptive behavior disorders (DBD) in preschoolers1. This way, treatment effects are not only measured in an indirect way, through information of caregivers, but also in a direct observation in the clinical setting. However, the age range of the children in the TRACE project is different from the preschoolers the DB-DOS was originally intented for. That’s why the TRACE project added several tasks to the original DB-DOS, to make sure it elicits disruptive behaviours, as well as hyperactivity and impulsivity, and to make it suitable for older children. During the current trial we try to find out if the DB-DOS is also a valid measurement for older children, aged 5-12 years.

The DB-DOS uses three different interactional contexts: parent-child context, examiner-child context and parent-examiner-child context. Children will be asked to complete different tasks. Some are rather boring, or frustrating, to see if this may elicit attention problems, hyperactivity, impulsive behaviour or disruptive behaviors. The DB-DOS contains, for example, some tasks which can evoke anger or sadness and some tasks where children get the chance to cheat. The reaction of the child is observed from behind a one-way screen. The observation lasts about 60 minutes and afterwards the observed behavior is scored by the examiner through a coding system. With more evidence-based instruments, mental health problems can be targeted more efficiently and reliably.

Our final goal is earlier interventions which prevent mental health problems in these children getting more severe and spreading through other domains such as school, work, or social contacts.

We will keep you posted about the results of the DB-DOS in the TRACE project!

REFERENCE
1 Bunte, T. L., Laschen, S., Schoemaker, K., Hessen, D. J., Van der Heijden, P. G. M., & Matthys, W. (2013). Clinical Usefulness of Observational Assessment in the Diagnosis of DBD and ADHD in Preschoolers. Journal of Clinical Child & Adolescent Psychology, 42(6), p.p. 749-761.
http://dx.doi.org/10.1080/15374416.2013.773516

 

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Recently, the idea that gastrointestinal microbiota are able to affect host behaviour is gaining momentum and it is based on studies conducted with animal models but also in humans with neurological disorders. However, the mechanisms that underlay this complex interplay between gut, brain and microbiota are not completely understood. Here we discuss recent findings on how microbial products could potentially affect the gut-brain axis.

Intestinal microbiota grow through the fermentation of undigested carbohydrates that end up in the large intestine. It was shown that absence of microbes or disruption of the microbiota, led to increased populations of impaired microglia cells in mice. Microglia cells are the primary effector cells for immune signalling to the central nervous system. The presence of a complex microbiota community, was shown to be essential for proper microglia maturation and function [1].

The main products of microbial fermentation in the gut are; acetate, propionate and butyrate, collectively known as short chain fatty acids(SCFA’s). Their beneficial role in human physiology have been well described, and recently evidence suggests that these molecules are able to cross blood brain barrier [2]. Moreover, gut microbiota have been associated with the brain barrier integrity. Mice raised in absence of bacteria are reported to have reduced brain barrier integrity. Once colonized with either a butyrate or an acetate/propionate producing bacteria, significant improvements were reported in the barrier [3]. Notably the integrity of the blood-brain barrier from the germ free mice was able to be restored through the oral administration of butyrate.

Gut_Microbes and Mental HealthSCFA’s are among the molecules having the privilege to cross the blood brain barrier and access the brain directly, their role should be studied in detail.

Recent studies also demonstrate that gut microbes regulate levels of intestinal neurotransmitters. The enteric nervous system interacts with a plethora of neurotransmitters (more than 30 have been identified so far.) Actually, the bulk of serotonin production ~90%, a neurotransmitter associated with mood and appetite is located in the gut. Specialized cells known as enterochromaffin cells are the main serotonin producers in the gut. In the absence of intestinal microbiota gastrointestinal serotonin levels are depleted. However, they can be restored by the addition of a specific spore forming consortium of intestinal bacteria. Specific bacterial metabolites have been reported to mediate this effect [4].

Other intestinal microbiota have been reported also to regulate the levels of the GABA neurotransmitter. Reduced levels of GABA have been associated with anxiety, panic disorder and depression. Bacterial GABA producers have been known to exist for years but it was not until 2016 that a gut bacteria was identified as GABA consumer [5]. For example, decreased levels of bacterial GABA producers were identified in a human cohort of depressed individuals. Studies in mice reinforce these findings. Intervention with the lactic acid bacteria Lactobacillus rhamnosus (JB-1) in healthy mice reduced anxiety related symptoms (accompanied by a reduction in the mRNA expression of GABA receptors in the Central Nervous System.) Lactic acid producing bacteria have also been reported to produce GABA in several food products such as kimchi, fermented fish and cheese [6].

Collectively, our gut microbiota encodes for ~100 times more genes than the human genome. The potential for some of these microbial genes to produce compounds able to interact with the nervous system and regulate critical pathways implicated in the gut brain axis is realistic and worth being explored.

Authors Prokopis Konstanti, MSc and Clara Belzer, PhD are working in the Department of Molecular Ecology, Laboratory of Microbiology, Wageningen University, Netherlands.

Footnotes

  1. Erny, D., et al., Host microbiota constantly control maturation and function of microglia in the CNS. Nature neuroscience, 2015. 18(7): p. 965-977.
  2. Joseph, J., et al., Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia? Frontiers in Neuroscience, 2017. 11(155).
  3. Braniste, V., et al., The gut microbiota influences blood-brain barrier permeability in mice. Science translational medicine, 2014. 6(263): p. 263ra158-263ra158.
  4. Yano, J.M., et al., Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 2015. 161(2): p. 264-276.
  5. P. Strandwitz, K.K., D. Dietrich, D. McDonald, T. Ramadhar, E. J. Stewart, R. Knight, J. Clardy, K. Lewis; , Gaba Modulating Bacteria of the Human Gut Microbiome. 2016.
  6. Dhakal, R., V.K. Bajpai, and K.-H. Baek, Production of gaba (γ – Aminobutyric acid) by microorganisms: a review. Brazilian Journal of Microbiology, 2012. 43(4): p. 1230-1241.

 

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