“Tell me what you eat and I will tell you what you are”

Silke Matura is a researcher at the Klinik für Psychiatrie, Psychosomatik und Psychotherapie Klinikum der J.W.Goethe-Universität in Frankfurt, Germany. She will be speaking at the 33rd ECNP Congress Virtual, 12-15 September 2020 as part of the symposium “Mediterranean diet, probiotics and micronutrients: can they improve mental health?”

The PROBIA study is part of the Eat2beNICE project, which is an EU-funded research consortium that studies the connections between gut microbiota, diet, and exercise to formulate nutrition and lifestyle recommendations for brain health. ECNP is one of the partners that supports the Eat2beNICE project. Dr Matura talks to ECNP press officer Tom Parkhill about the PROBIA project and how it aims to look at the effect of probiotics on mental health.

Dr Matura, firstly, how would you describe a probiotic?
A probiotic is simply a live microorganism which is believed to have an effect on health by restoring gut flora. Evidence for their effectiveness is so far limited or anecdotal, but it is interesting enough for us to undertake this study, which is an RCT looking at the effect of probiotics on impulsiveness and temper, specifically in ADHD sufferers.

What’s the background to this study?
We know that ADHD patients tend to gain weight, and many are overweight or obese. Increased impulsivity is one of the core symptoms of ADHD and this impulsiveness drives ADHD patients to eat differently; they tend to snack on more energy dense foods, containing sugar and fat,. There are many pharmacological interventions to reduce impulsiveness; our study is designed to see if non-pharmacological interventions can reduce impulsiveness.

What have you done?
This is part of the Eat2beNICE study, which looks more generally at the effect of nutrition on mental health. The PROBIA study has three study centres, in Spain, German and Hungary. We hope to include 180 patients who suffer from either ADHD or Borderline Personality Disorder (who also tend to be impulsive). All patients need to be highly impulsive to be enrolled.

How do you measure impulsiveness?
We use a self-reporting questionnaire, the Affective Reactivity Index questionnaire, with questions such as “I am easily annoyed by others”, “I stay angry for a long time”, or “My irritability causes me problems”. It’s a range of questions centres around temper and irritability. Impulsiveness itself we assess with the UPPS-P Impulsive Behaviour Scale, which is also a self-report questionnaire measuring different aspects of impulsivity such as a lack of perseverance (inability to remain focused on a task) or sensation-seeking (tendency to seek out novel and thrilling experiences). Examples of sensation-seeking might be excessive gambling or skydiving. Although impulsive behaviour can result in a lot of problems, there are also examples of adaptive impulsivity like the ability to make fast decisions.

Is this just temper or is it more general impulsiveness, such as gambling?
Well we’re also looking at adaptive and maladaptive impulsivity. Being able to make fast decisions would be an example of adaptive impulsivity. Maladaptive impulsivity manifests itself in thoughtless or premature behaviour.

So this is an RCT, how is it constructed?
Firstly volunteers suffering from ADHD or Borderline Personality Disorder are screened to make sure that they are appropriate for the trial. There is a range of standard tests for impulsiveness, but in this study we also look at the gut microbiome, so we also take a stool sample. Volunteers are randomly assigned to the control or intervention group, with the intervention group taking probiotics. Previous studies had shown that probiotics can influence psychological variables, in this case we are using probiotics and prebiotics, by which we mean that fermentable fibres are included in the product. One of the strengths of this study is that we do a lot of assessments, the study group is extremely well phenotyped.

This seems to be part of a larger idea, the idea that “You are what you eat”. Do you see this applying to a wider population?
We see more and more evidence that what we eat influences how we feel, and that the gut influences the brain. The PROBIA study is aimed at a single variable, so we need to look at what might help a specific patient group. We don’t expect to see huge differences in the general population.
We know that the variety of bacteria in the microbiome decreases as people eat a more energy-rich, Western-type diet. We also find different bacteria, so a Western diet will result in a different gut microbiome than, say, a Mediterranean diet.

What has COVID-19 done to the trial?
Well, we couldn’t see patients for around two months. This is a study, not an urgent clinical situation, so we had to stop patients coming to the hospital to participate in the study. We began to recruit patients again in mid-May. Fortunately we have a lot of medical students here in Frankfurt who are involved in the study, and they have been great in staying involved. In fact we found that things seem to have improved, maybe people are happy just to have a little more human contact as the COVID situation evolves. For many ADHD patients the outpatient clinics have been closed, so now we have restarted it seems to have become easier to recruit patients. It’s a two-year study, but the patients are recruited sequentially, and participate in the trial for 10-week periods.

What will you present at the ECNP Congress in September?
I will present the design and the current status of the PROBIA study. Since this is a double-blind randomised trial, we do not know the effect of the intervention until the work is unblinded. This will happen at the end of the study – so right now we have no information about whether the mixture of probiotics and prebiotics helps to reduce impulsivity in our patients.

If you do find positive results, how would you take this study forward?
Actually, we’d be interested to look at the effect of the probiotic on the gut microbiome, not only for ADHD, but also for conditions like depression. I’d be really interested in seeing if altering the gut microbiome by dietary intervention alters psychological wellbeing.

Symposium
S.03 – Mediterranean diet, probiotics and micronutrients: can they improve mental health?
Saturday, 12 September, 14.20-15.30

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