The transcriptomic fingerprint of anxiety reduction: what is the role of genetic liability for depression?

Repeated exposure to stressors is a method used in treatments of anxiety, effective in around 50% of patients. It may be effective, in part by changing gene expression in blood cells because immune responses in blood are linked with anxiety. Yet, little is known of how gene expression in blood is changed by this type of anxiety reduction. We want to know how gene expression in blood contributes to anxiety reduction following repeated exposure to social stress. Building on recent findings that genetic liability for depression predicts poorer treatment response in anxiety, we will also determine whether genetic liability for depression modulates gene expression and anxiety reduction. To this end, we will prospectively recruit 100 individuals with extremely High (N=50) or Low (N=50) genetic liability for depression. We predict poorer anxiety reduction in the group with High than Low genetic liability for depression. Next, we will identify the genes where expression changes with anxiety reduction. We predict less changes in these genes’ expression in the High compared to the Low genetic liability group. Identifying gene expression changes associated with exposure induced anxiety reduction could give important clues to new biological pathways of relevance to anxiety treatment. Understanding how genetic liability for depression influences gene expression associated with anxiety reduction will also inform on why anxiety is more resistant to change in some people than others.