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Emotion regulation as a transdiagnostic intervention target

Our emotions control our behavior – but we can influence type, intensity and duration of emotions. Difficulties with emotion perception and regulation are characteristic for mental disorders, such as attention deficit / hyperactivity disorder (ADHD), autism, disruptive behavior disorders, borderline personality disorder, non-suicidal self-harm and addictions. Emotional regulation problems can not only impair mental health, but also physical health. This is reflected, for example, in an increased risk of cardiovascular disorders and metabolic diseases.


Figure 1:

Path diagram showing the relationship between ADHD symptoms, neuropsychological performance and emotional lability - controlled for gender, age and intelligence (adapted from Banaschewski et al., 2012). The arrows indicate the direction of the influence.

Various studies have shown that early adverse experiences can impair the regulation of emotions and behavior (Herzog and Schmahl 2018). Emotional and behavioral dysregulation is associated with brain alterations, such as changes in gray matter volume. These alterations appear to contribute to the development of anxiety symptoms or disruptive behavior disorders (Figure 2; Spechler et al., 2019).


Figure 2:

Path diagram of the relationship between anxiety symptoms and disruptive behavior disorders, the volume in the gray matter of the right orbitofrontal cortex and emotional and behavioral dysregulation (adapted from Spechler et al., 2019). The arrows indicate the direction of the influence.

Such results can now inform therapeutic targets to train or adapt the ability for emotional and behavioral regulation in the case of mental disorders (e.g., BMBF-ESCA-Life;; BMBF-STAR; Thus, modification the activation of certain regions and neurobiological pathways in the brain (e.g., via neurofeedback) may help to improve emotion regulation. We have already successfully used such procedures for depression, borderline disorders, self-harm and addictions (see Fig. 3). Furthermore, dialectical behavior and trauma-focused group interventions have proven to be relevant and are particularly effective for people with disruptive behavior disorders (e.g. FemMat-CD).


Figure 3:

Modulation of fronto-limbic activity and emotion regulation by means of neurofeedback (real-time fMRI) in patients with borderline disorder and non-suicidal self-harm. Four training sessions of 30 minutes each lead to a reduction in amygdala activity and improved limbic-prefrontal connectivity (bottom left) as well as an improved emotional stability (reduction in the variability of emotional fluctuations) (bottom right).

Improvement of emotional regulation is not only an important component of interventions to treat mental disorders, but also central focus of mental disorder prevention programs (DUDE; com. can, ).


Banaschewski, T., Jennen-Steinmetz, C., Brandeis, D., Buitelaar, JK, Kuntsi, J., Poustka, L., Sergeant, JA, Sonuga-Barke, EJ, Frazier-Wood, AC, Albrecht, B ., Chen, W., Uebel, H., Schlotz, W., van der Meere, JJ, Gill, M., Manor, I., Miranda, A., Mulas, F., Oades, RD, Roeyers, H ., Rothenberger, A., Steinhausen, HC, Faraone, SV & Asherson, P. Neuropsychological correlates of emotional lability in children with ADHD. J Child Psychol Psychiatry 53, 1139-1148 (2012).

Herzog, J., Schmahl, C.: Adverse Childhood Experiences and the Consequences on Neurobiological, Psychosocial and Somatic Conditions across the Lifespan. Frontiers in Psychiatry, 9, 420 (2018).

Spechler, PA, Chaarani, B., Orr, C., Mackey, S., Higgins, ST, Banaschewski, T., Bokde, ALW, Bromberg, U., Buchel, C., Quinlan, EB, Conrod, PJ, Desrivieres, S., Flor, H., Frouin, V., Gowland, P., Heinz, A., Ittermann, B., Martinot, JL, Nees, F., Orfanos, DP, Poustka, L., Frohner, JH, Smolka, MN, Walter, H., Whelan, R., Schumann, G., Garavan, H., Althoff, RR & Consortium, I. Neuroimaging Evidence for Right Orbitofrontal Cortex Differences in Adolescents With Emotional and Behavioral Dysregulation. J Am Acad Child Adolesc Psychiatry 58, 1092-1103 (2019).

Zaehringer, JK, Ende, G., Santangelo, P., Kleindienst, N. Ruf, M., Bertsch, K., Bohus, M., Schmahl, C., Paret, C. Improved emotion regulation after neurofeedback: A. single-arm trial in patients with borderline personality disorder. Neuroimage Clinical, 24, 102032 (2019)

"The great discovery of my generation is that people can change their lives by changing their mindsets." -William James-


Evidence-based psychopharmacotherapy and pharmacovigilance

Psychopharmacology and pharmacovigilance in children and adolescents

One focus of our prevention research addresses health risks related to psychopharmacotherapy in children and adolescents. When children and adolescents with mental disorders require medication, they are at a disadvantage compared to adults. For many substances, there is currently a lack of data on the efficacy, (long-term) safety and age-appropriate recommendations for dosages or serum concentration ranges. The affected children are thus exposed to a higher risk of adverse drug effects, especially if several drugs are administered at the same time (polypharmacy) or if active substances are administered that are not approved for the age group or indication (off-label use).



Schematic passage of a drug and factors modifying the effectiveness and tolerability of a drug. Children with need for psychopharmacological treatment display developmental variation compared to adults both in pharmacodynamics and pharmacokinetics. Pharmacovigilance strategy including Therapeutic Drug Monitoring are necessary to increase safety, effectiveness and tolerability.

Despite these considerable uncertainties, psychotropic drugs are prescribed to minors by various professional groups such as psychiatrists, paediatricians, neurologists and general practitioners, thus requiring an interdisciplinary approach in dealing with the challenges described. CHILDhealth researchers were pioneers in the introduction of therapeutic drug monitoring (TDM) in Germany as a proactive pharmacovigilance strategy in everyday clinical practice and, at the same time, as a practical research area. For this purpose, the 'Competence Network Therapeutic Drug Monitoring' was founded, which now has 48 members in 5 European countries and has established the first internet-based patient registry in the field of pediatric psychopharmacology in Germany (funded by the BMBF). This laid the groundwork to carry out the international, multicenter pharmacovigilance study 'TDM-VIGIL' funded by the Federal Institute for Drugs and Medical Devices (BfArM), which prospectively assesses the safety of (off-label) use of antidepressants, antipsychotics and stimulants in around 1200 children and adolescents in everyday clinical practice. In the KIDsafe project funded by the G-BA's innovation fund, a digital evidence-based information tool is being tested in clinical practice in order to reduce side effects.

We have also played a decisive role in several other research consortia on psychopharmacology: We examined the long-term safety of methylphenidate in the treatment of children and adolescents with ADHD as part of the European Union-funded project "ADDUCE", which also informed the adaptation of national ADHD S3 guidelines. The EU project PERS examined safety aspects for the treatment of children and adolescents with risperidone. The EU project STOP dealt with various aspects of drug-associated suicidality. The EU project TACTICS examined the efficacy and safety of glutamatergic substances in the treatment of obsessive-compulsive disorder and autism spectrum disorders. In addition, CHILDhealth members are national representatives of child psychiatry as part of the German-Net-Paed / EU-C4C initiative.

In summary, our experience from two decades of pharmacovigilance research in children and adolescents has influenced the national guidelines for TDM of neuropsychopharmaceuticals (AGNP e.V.) and provided first evidence-based data for the definition of age-adjusted serum concentration ranges of various substances.
In a specialized TDM laboratory (Würzburg location) we are already offering a state-of-the-art TDM service using mass spectrometry and specialist medical reports. In the near future we will also be able to perform pharmacogenetic analyses.

With this, CHILDhealth aims to promote the evidence-based psychopharmacotherapy in children and adolescents and to implement pharmacovigilance strategy across the board in everyday clinical practice.


Anker 2

Microbiome-host interaction as avenue for prevention of developmental disorders

The research field addressing the interplay of early priming of the immune system related to the microbiome opens up a novel and innovative insight into how our early environment shapes a child’s development. Our research has critically promoted our understanding how early adverse constellations lead to poor health outcomes and has fueled research on the lasting impact of altered microbiome on brain development and the manifestation of mental disorders. 

We hereby focus on highly vulnerable preterm infants who are prone to infections, sepsis and are frequently exposed to early and repeated antibiotic medications with potential to disrupt the microbiome environment during critical time windows. Preterm children are observed under quasi-experimental conditions in intensive care units and as such provide an excellent cohort to study gene-environment interactions for developmental trajectories and risk and resilience signatures for somatic and mental disorders. 

For example, our investigations in both human cohorts and animal models corroborated the crucial role of the S100A8/9 protein for the priming of early immune responses, for the healthy development of the gut microbiome, and for the prevention of sustained inflammation in children. Our findings may explain some of the unique effects of breastfeeding given that mother’s milk is exceptionally rich in the S100A8/9 protein. Our research has strongly influenced recent recommendations regarding breastfeeding to preterm infants. Apart from the biological beneficial effects through breastfeeding, we are interested in the positive effects through the intensive interaction between the children and their mothers.

We are hence engaged in translating our findings to clinical supplementation trials addressing S100 A8/9-deficient individuals. Following this line of thought, we have initiated the ongoing translational lighthouse project BMBF-PRIMAL, a placebo-controlled multicenter-RCT, which explores the effect of multistrain probiotics on the development of gut dysbiosis and immune dysregulation in preterm infants. By integration of other neonatal network studies (BMBF-GNN, DFG-IRoN) in CHILDhealth, we will have the unique opportunity to assess the longitudinal effects and therapeutic malleability of immune-microbiome and neurodevelopmental signatures. These trials will inform us as well, how the protein contributes to the stabilization of the gut-brain-axis and the prevention of neurodevelopmental disorders.
In the same vein, we have targeted therapeutic and preventive modification of the microbiome within the projects EU-Eat2beNice and DFG-IRoN aiming at beneficial reprogramming of immunological risk constellations and restoration of protective patterns. Facilitated by our cutting-edge RNA-technology CHILDhealth is in a unique position to elucidate the systemic and tissue-specific effects of dysbiosis and immune signatures and to explore RNA-based interventions beyond immunizations.

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