Serotonergic Modulation of Impulsivity

• Applicants: Privatdozentin Dr. Susanne Neufang; Professor Dr. Marcel Romanos
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 404502177

Attention-Deficit Hyperactivity Disorder (ADHD) is a heterogenous disease that frequently presents with co-occurring psychiatric disorders, e.g. conduct disorder and anxiety. By bridging the fields of basic research and clinical science, translational studies have increasingly gained importance, nurturing our understanding of the underlying mechanisms of comorbidities and exploring novel treatment perspectives. In the case of the serotonin-catalizing tryptophan hydroxylase-2 (TPH2) gene, the null mutant mice (Tph2-/-) have been discussed as candidate model for ADHD. Variants of the TPH2 gene hav been associated with ADHD, increased impulsive behavior, increased aggression and altered anxiety behavior.Derived from the combined phenotypic alterations in anxiety, impulsivity and aggression in the TPH2 KO mouse model and clinical findings, the aim of this study is to quantify these phenotypic dimensions in a clinical pediatric sample of 250 ADHD patients and typically developing children. All participants will be (a) genotyped for the TPH2 (G-703T; rs4570625) variant, (b) phenotyped for impulsivity, aggression and anxiety as suggested by the international Research Domain Criteria (RDoC) and (c) examined using the 5-choice serial reaction time task in the fMRI scanner. In a second step, the mediating and moderating interaction of the dimensional phenotypes will be characterized by clinical, behavioral and neural parameters. Using an adapted version of the reverse phenotyping approach, this study will provide insight into the mechanisms of phenotypic complexity in comorbid disorders associated with ADHD. Broader societal, political and scientific impact may be expected from the findings in terms of developing age-adapted targeted intervention and prevention programs in ADHD.

• DFG Programme: Research Grants