Negative emotion regulation in alcohol use disorder - (Epi)Genetic modulation of fear extinction, negative emotion, reward and stress processing

• Applicant: Dr. Katrin Charlet
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 386105629

The primary goal of this study is to evaluate the role and interaction of (epi)genetic factors, early life stress (ELS) exposure, and alcohol use disorder (AUD) on neuronal mechanisms of fear conditioning and extinction. Since one of the environmental factors most associated with the development of AUD is exposure to ELS, the central hypothesis is that participants with AUD and ELS show disrupted fear extinction, which in turn is assumed to be related with severe AUD phenotypes. Therefore, individuals with and without AUD and with or without ELS will be evaluated for fear conditioning and extinction using shock conditioning (combined with fMRI imaging that utilizes galvanic skin response). Additionally, all participants will undergo whole-genome methylome analyses to assess genome wide methylation patterns. Genotyping of variants in candidate genes implicated in the biology of fear conditioning/extinction will be carried out.Identification and characterization of reliable measureable endophenotypes of fear extinction in AUD/ELS helps to elucidate essential AUD mechanisms and thus could provide new avenues for treatment of AUD; namely developing interventions that “normalize” abnormal fear extinctions. These interventions could be for example, psychotherapeutically based or molecular by targeting genetic/epigenetic pathways potentially identified.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Falk W. Lohoff