Genetic polymorphisms involved in fear acquisition and extinction: a study in patients with anxiety disorders
background To shed light on the etiology of anxiety disorders by investigating underlying fear acquisition and extinction mechanisms, and their genetic underpinnings.
aim 1. To study fear acquisition, inhibition and extinction mechanisms as endophenotypes of anxiety disorders 2. To study the genetic underpinnings of fear acquisition and extinction 3. To explore relationships between genotype, fear acquisition, inhibition and extinction and treatment outcome.
method One hundred and fifty subjects with anxiety disorders and 150 healthy controls will be screened using standardised instruments on qualitative and quantitative measures of anxiety, depression, panic, and agoraphobia. A fear acquisition, extinction and context-learning paradigm using a virtual reality task is performed at baseline to assess fear acquisition and extinction using several contextual cues, in a quasi-experimental design. In all subjects dna is collected using standardised procedures. Patients are treated using state-of-the-art cbt, and outcome as measured directly post treatment.
results This is work in progress, and therefore at the conference an overview of the literature is provided.
conclusion Hopefully, the present study will provide answers to the following questions: to which extent are dysfunctional fear acquisition and extinction mechanisms related to the anxiety disorder group when compared to controls? To what extent do fear acquisition and extinction mechanisms predict treatment outcome in patients with anxiety disorders? To what extent are genetic polymorphisms in serotonergic, dopaminergic, glutamatergic and neurotrophic pathways related to variations in fear acquisition and extinction parameters? What is the direction of the relationship between genetic polymorphisms, fear acquisition and extinction parameters and anxiety disorder symptom severity and outcome?