Lay summary
Background: Obsessive-compulsive disorder (OCD) is the world's fourth most common psychiatric disorder with a frequent onset in childhood or adolescence and poor long-term prognosis. Children and adults with OCD suffer from unrealistic and excessive recurrent and intrusive thoughts (obsessions) which are usually accompanied by stereotypic repetitive behaviours (compulsions). Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequent psychiatric disorders in children and adolescents affecting up to 5-7% of the children and is characterized by inappropriate levels of inattention as well as hyperactivity and/or impulsivity. The causes and pathophysiology of these highly heritable disorders are still unknown. Brain imaging studies point to dysfunction of specific but partly overlapping brain circuits at rest and during cognitive tasks. Aims: Our aim is to better understand the core problems in juvenile OCD - impaired action monitoring and cognitive flexibility - by measuring when and where critical brain function fail, how these problems are affected by genetic and neuropsychological profiles, and how they contrast with the partly opposite problems of children with ADHD. Context and impact: Integrating findings from two complementary functional imaging approaches allows for the first time to compare the specific brain dysfunctions in OCD and ADHD at the same time point and in the same brain circuits. This approach will provide a new level of understanding of the partly parallel and partly opposite core dysfunctions in these disorders. Neuropsychology, genetics and biochemical studies will complement the neuroimaging investigations to determine sensitive biomarkers. In the long run, OCD diagnostics and treatment will be improved by the combination of biomarkers from neuroimaging, neuropsychology and genetics. Experimental Design and Methods: A group of 12-16 year old non-medicated children with OCD will be compared to matched patients with ADHD and a healthy control group. Brain networks involved in action monitoring and cognitive flexibility will be examined with multimodal brain imaging. All participants will take part in neuropsychological testings, and in electroencephalography (EEG) and functional/structural magnetic resonance (MRI) sessions. The gene analyses will add a multi-level perspective on the question whether brain activation of patients with OCD and ADHD is modulated by genetic variants.