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

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

Why is this finding so important?

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

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

Why are our researchers excited about this?

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

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

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

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

Further Reading

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

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

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What is inflammation?

Inflammation is the response of the body’s immune system against external factors that can put your health in danger. When this system feels it is attacked by something that may harm your health, it activates some molecules that are called cytokines in order to neutralize or avoid any damage so you can be safe.

Why is inflammation bad? What does it do?

Inflammation isn’t bad by itself, since its purpose is to protect our body. In some cases however, when the duration of this response is extended for too long- I’m talking about years- it can cause harmful effects to your health. Especially, it can affect the brain by active transport of cytokines throughout this organ.

Neuro-inflammation may occur if this process continues past early stages. Neuro-inflammation plays an important role in the development of mental diseases such as attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, depression, anxiety, bipolar disorder (BD), and obsessive-compulsive disorder (OCD), where elevated levels of inflammation have been found(1).

What causes inflammation? 

Inflammation can occur by different factors. Some of them could be: pathogens, injuries, chronic stress, and diseases like dermatitis, cystitis or bronchitis to mention a few.

Nutritional factors like overweight and poor diet quality can also trigger this process by increasing fat accumulation in our cells and damaging them (2). The exact mechanisms that are involved in these processes are still in research.

What decreases inflammation?

Research has found that adhering to a healthy diet, like the Mediterranean diet, characterized by high intake of fruit, vegetables, whole grains, fish, lean meats and nuts, can decrease inflammation and protect you against depressive symptoms and anxiety (3,4).

There is evidence that prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) can also help lowering inflammation. In addition, you should avoid eating pro-inflammatory foods that have been found to increase the risk of inflammation, and with it mental disorders. Some of these are refined carbohydrates, beverages with a lot of sugar added like soda, juice and sports drinks, processed meat and foods high in saturated fats (5).

What are anti-inflammatory foods

Anti-inflammatory foods are the contrast of pro-inflammatory foods. These are foods that have been found to promote or induce low levels of inflammation in our body, which may protect us against neurological disorders. Briefly, these foods include fruits, vegetables, olive oil, fish and spices like curcuma (turmeric).

Here’s what YOU can do to minimize inflammation and improve your mental health.

Inflammation and Foods

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

Sources

  1. Mitchell RHB, Goldstein BI. Inflammation in children and adolescents with neuropsychiatric disorders: A systematic review. J Am Acad Child Adolesc Psychiatry [Internet]. Elsevier Inc; 2014;53(3):274–96. Available from: http://dx.doi.org/10.1016/j.jaac.2013.11.013
  2. Ogłodek EA, Just MJ. The Association between Inflammatory Markers (iNOS, HO-1, IL-33, MIP-1β) and Depression with and without Posttraumatic Stress Disorder. Pharmacol Reports [Internet]. 2018;70:1065–72. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1734114017305923
  3. Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry [Internet]. Springer US; 2018;1. Available from: http://www.nature.com/articles/s41380-018-0237-8
  4. Phillips CM, Shivappa N, Hébert JR, Perry IJ. Dietary inflammatory index and mental health: A cross-sectional analysis of the relationship with depressive symptoms, anxiety and well-being in adults. Clin Nutr. 2017;37.
  5. Shivappa N, Bonaccio M, Hebert JR, Di Castelnuovo A, Costanzo S, Ruggiero E, et al. Association of proinflammatory diet with low-grade inflammation: results from the Moli-sani study. Nutrition. 2018;54:182–8.

 

 

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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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