Impact of COMT, DIRAS2, and LPHN3 on emotional processing in ADHD

• Applicants: Professor Dr. Thomas Ethofer; Professor Dr. Andreas Jochen Fallgatter; Professorin Dr. Vanessa Nieratschker
• Subject Area: Biological Psychiatry
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258696339

Attention deficit hyperactivity disorder (ADHD) is highly heritable and its core symptoms including inattention, hyperactivity, and impulsivity can also be present in adulthood severly compromising the quality of life of affected individuals. For ADHD patients, processing of emotional signals is particularly challenging: On the one hand, impaired judgments of non-verbal emotional signals in voices and faces have been shown in both children and adults with ADHD. On the other hand, such socially relevant signals have the potential to act as distractors that can interfere with cognitive tasks. Recent results using functional magnetic resonance imaging (fMRI) demonstrated increased responses in the amygdala of children with ADHD during judgment of emotional faces. The neural correlates of the disturbed perception of emotional signals in adult ADHD as well as their genetic origins, however, are unknown so far. Genetic imaging studies in healthy participants could demonstrate a crucial role for the val158met genotype of the catecholamin-O-methyl transferase (COMT) during processing of emotional stimuli. Furthermore, it has been shown that the high-activity COMT genotype leading to decreased dopaminergic activity in the prefrontal cortex is associated with impaired social cognition and antisocial behavior. At behavioral level, a significant genetic impact on social behavior has been recently described in ADHD for the ADHD-associated genes GTP-binding RAS-like 2 gene (DIRAS2) and latrophilin 3 (LPHN3). It is the aim of this project to identify endophenotypes in ADHD which are associated with impaired social cognition. To this end, we plan to combine structural and functional MRI with molecular genetics (imaging genetics). Successful prediction of impaired social cognition based on genetic and neuroimaging risk factors might open a window for an early and individualized therapy in this patient group.

• DFG Programme: Research Grants