Autism spectrum disorder (ASD) is a severe, lifelong and highly cost-intensive neurodevelopmental disorder characterized by impairments in social interaction (e.g. deficits in appropriate eye contact, facial expression, emotion perception, gesture, social and emotional reciprocity) and communication (e.g. echolalia, stereotyped language, reduced reciprocal conversation), as well as restricted and repetitive behaviour (e.g. rigid preferences for routines, repetitive motor mannerisms). Currently, the prevalence of ASD in children and adolescents as well as in adults is approximately 1%.
The ASD-Net is a consortium containing five major research projects been processed by different research groups distributed throughout Germany, which are the Department of Child & Adolescent Psychiatry of the Philipps-University Marburg, Central Institute of Mental Health in Mannheim, the Department of Psychiatry of the Charité Berlin, the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, the Department of Health Economics & Health Services of the University in Bremen and finally the Department of Child & Adolescent Psychiatry of the University Clinic Carl Gustav Carus and Technical University Dresden. This consortium integrates advanced and innovative diagnostic and therapeutic strategies with evidence from basic research, with the overarching aim to reduce individual distress, harm, and social disability of patients and costs for the health care system in Germany.
Within the ASD-Net we manage the Project 1a as principal investigator (PI):
This project contains the development and evaluation of an economical screening instrument and internet-based training tool for the early and valid detection of ASD diagnosis in children and adolescents (Project 1a). More detailed, the existing screening instruments for ASD are, in fact, sensitive and able to accurately identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioral disorders (such as attention-deficit/ hyperactivity disorder , language disorders, intellectual disabilities, anxiety disorders and others).
In sum project 1a covers three aspects:
(1) The development of an economical and valid screening instrument on the basis of data of approx. 1,350 children and adolescents with ASD and the same number of patients with relevant differential diagnoses.
(2) The prospectively evaluation of this screening instrument in an independent sample of children and adolescents suspected of ASD.
(3) The development of an internet-based training tool, in order to accommodate different health care professionals (e.g. pediatricians, general practitioners, child and adolescent psychiatrists) with the newly developed screening instrument.
In addition we participate in the following projects:
Project 3a & 3b
While a growing number of studies support the efficacy of behaviour-based interventions in autism spectrum disorder (ASD), research on the combination of these psychotherapeutic interventions and pharmacological treatments strate¬gies is still sparse. Only a small number of studies so far have shown that administration of additional medication has the potential to enhance the effects of psychotherapeutic/behavioural therapies. To date, there is no effective medication avail¬able for the treatment of core deficits in ASD. In this respect, oxytocin (OXT) is of particular relevance in ASD, as it has been identified as a powerful enhancer of neural activity related to social cognition, the formation of social bonds and socially reinforced learning. Recent findings from genetic, animal and single-dosed intervention studies suggest OXT to be of therapeutic potential for the improvement of social deficits as well stereotyped, repetitive behaviour in ASD. Randomized controlled trials (RCTs) using stringent inclusion and exclusion criteria provide evidence that social skills training (SST) is effective in improv¬ing social competence and decreasing loneliness in children and adolescents with ASD. However, no study so far has tested the efficacy of OXT in combination with psychotherapeutic interventions like SST on the acquisition of social competence in ASD.
Moreover effects of an oxytocin enhanced social skill training (SST) should be particularly observable in brain regions associated with autism spectrum disorder (ASD) and oxytocin (OXT) like the social brain, particularly the amygdala, and the rewards circuits. We therefore apply a battery of fMRI tasks to examine the effect of OXT administration on neural activation in N = 100 participants before and after SST. We will delineate OXT specific modulation of the social brain using a Theory of Mind (ToM) task to activate the mentalizing network, an affective matching task particularly focusing on the amygdala, and a reward task combining both, social and non-social cues as well as social and non-social rewards. We will identify specific neurobiological mechanisms associated with therapy response as well as particular neurobiological signatures before treatment that are associated with treatment response. Results should further allow us to tailor treatment to different subtypes of ASD and finally to correctly allocate individuals to treatment settings.
ASD starts in childhood, continues across the lifespan, and requires complex and highly specialized health, educational, and vocational services for many years. Therefore, ASD is a cost-intensive disorder, which becomes more resource-consuming with increasing age. Recent research from the UK estimates the total ASD-related costs to be £ 34 billion a year, with lifetime costs for intellectually disabled individuals with ASD of £ 1.5 million. Fortunately, these costs can partly be countered by early behavioural interventions: Data from the Netherlands demonstrate long-term savings of approximately € 1.1 million per individual with ASD. Extending these costs to the whole Dutch ASD population, cost savings of € 109 - 182 billion have been estimated. For Germany, to date, there is no information on ASD-related costs. More information on cost distribution is needed to inform future models for efficient resource allocation in order to support individuals with ASD. Therefore, the objectives of this proposal are as follows: (1) to conduct a cost-of-illness study in order to draw a naturalistic picture of annual and lifetime ASD-related costs in Germany, (2) to model how ASD-related costs would be influenced by implementation of early therapeutic interventions, (3) to evaluate the cost-effectiveness of enhanced social skills training (SST, with oxytocin vs. placebo) (P3a), and (4) to assess pathways of health service use in first-time ASD diagnosis.
The project is funded by the „Bundesministerium für Bildung und Forschung“ For more information please refer to the website of ASD Net: http://www.asd-net.de/
Service Module (SM): (Epi) Genetics and imaging genetics in ASD
Little is known about the molecular mechanisms of how OXT impacts on a behavioural and/or neural level. In the light of the individual variability of OXT response, the consideration of individual factors like gender, genetic and epigenetic variations in studies investigating the efficacy of OXT administration in treatment of ASD are warranted5. In this project, we aim to identify which genetic and epigenetic factors are a) predictive at baseline for the patients’ treatment [OXT, social skills training (SST)+placebo, SST+OXT] outcome and b) associated with the response to acute and long-term OXT administration. By identifying implicated genetic factors and methylation changes, we will c) gain new insights into the molecular mechanisms underlying ASD and the OXT response. Data at baseline and after treatment will be analyzed not only with respect to the categorical diagnoses but also regarding behavioural and imaging sub-phenotypes.
In sum, we aim to investigate the following research questions:
Diagnosis: Is it possible to develop economical and valid screening instruments and an internet-based training tool for an early, sensitive and accurate detection of ASD in the primary care sector? (P1a, P1b)
Therapy: What are the acute and long-term effects of OXT treatment in ASD? Does an adjunctive application of OXT treatment with SST show promise in providing resources to the affected individuals and their families (P3a)? What are the mediators and moderators of OXT treatment on the level of behaviour (P3a, P3b), neural networks (P3b), and (epi) genetics (SM)?
Health economics: What are health economic costs of ASD in Germany? Do age, IQ and gender impact costs (P5)?