Subcortical and psychopathological correlates of catecholamine-modulated long term fear acquisition and extinction

• Applicant: Professor Dr. Erik M. Müller
• Subject Area: Personality Psychology, Clinical and Medical Psychology, Methodology ; General, Cognitive and Mathematical Psychology
• Term: from 2013 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234370960

In the project Catecholaminergic Mechanisms of Long-Term Fear Extinction four studies were conducted with N>200 multi-session measurements that included EEG, pharmacological manipulations of catecholamine activity and molecular genetic assessment of a catecholaminergic gene-variant (COMTVal158Met). These studies demonstrated that the long-term fear acquisition relates to oscillatory theta activity in the anterior midcingulate cortex, that the long-term fear acquisition is enhanced by the noradrenalin agonist yohimbine and that individual differences in long-term acquisition and extinction of fear are associated with COMTVal158Met. The results bring up new questions, which we attempt to answer with two additional studies during a subsequent funding period. Because the influence of yohimbine on the long-term fear acquisition was observed in peripheral but not electrocortical (i.e., EEG) fear markers, the goal of study 1 is to combine fMRI and yohimbine to clarify, whether subcortical fear-relevant structures like the amygdala mediate the effect of noradrenaline on long-term fear acquisition. N = 42 participants perform an fMRI-adapted variant of the two-day conditioning and extinction paradigm that was developed as part. Particpants receive 10 mg yohimbine or placebo (randomized and double-blind) after the acquisition phase. Brain activity to conditioned vs. non-conditioned stimuli during a subsequent extinction session and a recall test 24h later is compared between the yohimbin and placebo group. The goal of study 2 is to test, whether the observed indicators of long-term acquisition and extinction of fear provide potential risk markers for social anxiety disorder (SAD). In spite of many studies on short-term fear conditioning in anxiety disorders, it has been hardly investigated, whether anxiety disorders are characterized by more long-term stable fear acquisition and more labile fear extinction. Particularly such long-term learning- and consolidation processes, however, are of potential importance for the development and maintenance of anxiety disorders. Because the long-term fear conditioning of face stimuli should be of particular relevance for SAD, we aim to compare the long-term fear conditioning and extinction in N=20 participants with SAD and N=20 healthy controls. To further investigate the disorder specificity N=20 participants with panic disorder will also be tested. Together, the expected results provide important extensions to the results. They inform by which brain regions yohimbine potentiates long-term fear conditioning (study 1) and whether potentiated long-term fear conditioning is a potential risk factor for anxiety disorders (study 2).

• DFG Programme: Research Grants
• International Connection: USA
• Cooperation Partners: Professor Dr. Urs Nater; Professor Dr. Diego Pizzagalli, Ph.D.