Psychiatric disorders are among the leading causes of morbidity in Europe. The burden of those disorders to patients and their families as well as costs to society are enormous (1). Ironically, despite high socio-economic impact and immense suffering of patients and relatives, we still know very little about the etiology of these disorders, and no curative treatments have been developed. Particularly serious are disorders that have an early onset and cause impairments during the entire lifespan. The most common of such neurodevelopmental disorders are attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD).
ADHD and ASD are chronic neurodevelopmental disorders that start in early childhood and show a strong persistence into adulthood (ADHD: 65%; ASD: 80-90%). The prevalence of ADHD is about 5.3% in children and 2.5% in adults (2). The prevalence of ASD in both childhood and adulthood is about 1% (3,4). ADHD and ASD show strong clinical and etiological heterogeneity. The socio-economic impact of the disorders is high, not only due to costs related to treatment, but because individuals with ADHD and ASD also often fail to pursue an occupational career: adults with these disorders show higher rates of unemployment than adults on average, and there is a significant increase in substance use disorders, depression and anxiety disorders as well as aggression and personality disorders, especially in adults with ADHD (5). While the definition of ADHD and ASD has changed many times since these conditions were first described (6) these changes have not resulted in any breakthrough in clinical management - with one exception, in the DSM-5, it is now allowed to diagnose ADHD as co-occurring with ASD. In fact, both disorders frequently co-occur (7), with 20-50% of ADHD patients meeting criteria for ASD and 30-80% of ASD patients also having ADHD (8,9).
In contrast to most somatic diseases, no generally applicable para-clinical or biological tests are available to confirm neurodevelopmental diagnoses (10). Knowledge about fundamental disease mechanisms underlying such disorders and their overlap is missing, which has obvious consequences for their diagnosis and treatment. ADHD and ASD both present a high degree of familial aggregation. Based on twin studies, a heritability of 77% has been estimated for ADHD (11) and 80% for ASD (12). Both are multifactorial diseases involving multiple susceptibility genes of small individual effects that interact with environmental factors to increase disease risk. However, most of the risk factors, both genetic and environmental, have yet to be identified. In addition to the polygenic forms of the disorders, recent research shows that a certain, yet undefined proportion of cases is likely caused by more penetrant, rare genetic variants. Given the paucity of information on disease etiology, it is not surprising that current pharmacotherapy of ADHD and especially ASD – which was discovered serendipitously 50-120 years ago - is often inadequate. The presence of ADHD in ASD is also related to less effective treatment by behavioural therapy, and the ADHD treatment methylphenidate is less effective and showing more side effects in the presence of comorbid ASD (13).