An innovative study, led by the Psychiatry, Mental Health and Addictions group of the Vall d'Hebron Research Institute (VHIR) and the CIBER of Mental Health (CIBERSAM), has revealed that synbiotics, a combination of probiotics and prebiotics, are a promising tool to treat irritability in adults with Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD). The results have been published in Brain, Behavior, and Immunity.

Irritability is a complex and often persistent symptom, which significantly affects the quality of life of ADHD and BPD patients and, in severe cases, can increase the risk of suicide. "Current treatments fail to significantly improve the symptoms of irritability, which often manifest along with other emotional problems such as emotional dysregulation and impulsivity", explains Dr. Gara Arteaga Henriquez, from the Psychiatry Service of Vall d'Hebron University Hospital and researcher of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM.

Previous studies had suggested the potential of synbiotics in the emotional dysregulation associated with ADHD. In this context, the team launched a pioneering clinical trial to explore the benefits of synbiotics for the treatment of patients with irritability. The study involved patients from Vall d'Hebron University Hospital, Semmelweis University (Budapest, Hungary) and Goethe University Hospital Frankfurt (Germany).

The study included 180 patients aged between 20 and 65 years, of whom 113 with ADHD, 44 with BPD and 23 diagnosed with both pathologies. All of them had symptoms of irritability, and most of them were already taking other types of medication. One half of the patients received a placebo and the other half took a synbiotic. This compound included four types of bacteria (probiotic) and a set of sugars that are nutrients for the growth of the bacteria (prebiotic).

The research team analyzed the response to treatment after 10 weeks. A good response to treatment was considered to be present if there was a clinical improvement in the symptoms of irritability, according to the criteria of the medical professionals and the patient's experience. Thus, it was observed that in 19 patients (11% of the total) the levels of irritability were reduced: 15 of these (79%) had taken the synbiotic while only four (21%) had received the placebo. In all cases, good tolerance of the treatment was confirmed, with few side effects.

In addition, the synbiotics showed benefits in other symptoms, such as intense mood fluctuations, difficulty controlling emotional reactions, attention problems and stress levels. "This study provides promising preliminary evidence for the use of synbiotics in the treatment of irritability and other emotional symptoms in adults with ADHD and BPD", highlights Dr. Arteaga.

Analysis of inflammatory molecules in blood helps predict response to synbiotics

To understand why some patients respond to synbiotics and others do not, the study analyzed the relationship between the levels of some immune system molecules in the blood and the success of the therapy. "We think that synbiotics may act as regulators of the immune system and that the response to these treatments is influenced by the underlying inflammatory conditions of each individual", says Dr. Arteaga.

Among the molecules studied, RANK-L is particularly noteworthy: the results show that patients with low levels had a better response to treatment with synbiotics. "Apparently, when RANK-L levels in the blood are low, there is a higher baseline inflammation that can affect the brain. In these cases, synbiotics could help reduce this inflammation and therefore improve symptoms", comments Dr. Arteaga.

The authors emphasize the need for further research to confirm these results and to explore in depth the underlying mechanisms of these benefits. "These findings open the door to new personalized treatment approaches based on modulation of the intestinal microbiota for patients who do not respond to traditional treatments for irritability", assures Dr. Josep Antoni Ramos Quiroga, head of the Psychiatry Department at Vall d'Hebron University Hospital and of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM researcher, who explains that "our ultimate goal is that, based on a blood test where we measure the levels of inflammatory molecules, we can determine whether a synbiotic would be effective and offer an additional and complementary therapeutic option to existing therapies".

ADHD and BPD: two different disorders with common features

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder that primarily affects attention span, impulsivity and motor control. This pathology is mostly diagnosed during childhood, although in many individuals remains with an impact during adulthood.

On the other hand, Borderline Personality Disorder (BPD) is a condition characterized by significant emotional instability, intense and fluctuating interpersonal relationship patterns, and altered self-perception.

Although the specific symptoms of ADHD and BPD may vary substantially, both disorders partially share a biological basis and some common features, such as persistent irritability and emotional dysregulation.

A clinical trial with an innovative approach to tackling irritability

This study is groundbreaking because it addresses an under-researched symptom, such as irritability, through a basket clinical trial, which allows the study of two different disorders, but with common symptoms. In this case, it allows the study of irritability in ADHD and BPD, in a way that favors a broader and more detailed vision. These types of studies are frequent in the field of oncology to study different tumors with common characteristics.

In addition, unlike other studies, the results of this trial incorporate both the clinical assessments of the healthcare professionals and the self-assessments of the patients. In order for a person to be considered a responder to treatment, both evaluations must coincide. "This method provides a more complete and reliable assessment of treatment response, avoiding errors and offering a more accurate picture of the efficacy of the synbiotic", concludes Dr. Arteaga.

This study was supported by the European Commission and funded by the European's Union Horizon 2020 Research and Innovation program under grant agreement number 728018.