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

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

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

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

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

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

REFERENCES:

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

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

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

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

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

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

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

 

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Maladaptive or uncontrolled impulsivity and compulsivity lead to emotional and social maladjustment, e.g. addiction and crime, and underlie psychiatric disorders. Recently, alterations in microbiota composition have shown to have implications for brain and social behaviors as we have been explaining in our lasts blogs. The microbiota-gut-brain axis may be involved in this process but the mechanisms are not fully identified (1). The supplementation of probiotics can modulate the microbial community and now has been suspected to contribute to ameliorating symptoms of a psychiatric disease with possible influence on social behaviors (2). To date, no randomized controlled trial has been performed to establish feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. This gave us the idea to perform a study to investigate the effects of supplementation with probiotics, working with adults with Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD) which in most cases present high levels of impulsivity, compulsivity and aggression.

Probiotics for healthWe call our project PROBIA, which is an acronym of “PROBiotics for Impulsivity in Adults”. This study will be performed in three centers of Europe including, Goethe University in Frankfurt, Semmelweis University in Budapest and Vall d’Hebron Research Institute (VHIR) in Barcelona, the coordinator of the clinical trial. We are planning to start recruiting patients in January of 2019 and obtain the results in 2021. In our study, we will explore the effects of probiotics by measuring the change in ADHD or BPD symptoms, general psychopathology, health-related quality of life, neurocognitive function, nutritional intake, and physical fitness. The effect of the intervention on the microbiome, epigenetics, blood biomarkers, and health will be also explored by collecting blood, stool, and saliva samples.

We are looking forward to having the results of this amazing study in order to understand the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If improvement effects can be established in these patients, new cost-effective treatment will be available to this population.

 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. Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF. Microbiota is essential for social development in the mouse. Mol Psychiatry [Internet]. The Author(s); 2013 May 21;19:146. Available from: http://dx.doi.org/10.1038/mp.2013.65
  2. Felice VD, O SM. The microbiome and disorders of the central nervous system. 2017 [cited 2017 Oct 16]; Available from: https://ac.els-cdn.com/S0091305717300242/1-s2.0-S0091305717300242-main.pdf?_tid=b52750d8-b2ae-11e7-819b-00000aab0f02&acdnat=1508185089_58e99184d2c0f677d79ff1dd88d02667

 

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