Towards new approaches to disorders of fear and anxiety

Fear and anxiety are debilitating conditions that affect a significant number of individuals in their lifetimes. Understanding underlying mechanisms of these disorders affords us the possibility of therapeutic intervention. Such clarity in terms of mechanism and intervention can only come from an amalgamation of research from human to animal studies that attempt to mimic the human condition, both of which are discussed in this review. We begin by presenting an outline of our current understanding of the neurobiological basis of fear and anxiety. This outline spans various levels of organization that include the circuitry, molecular pathways, genetic and epigenetic components of fear and anxiety. Using these organizational levels as a scaffold, we then discuss strategies that are currently used to ameliorate these disorders, and forecast future interventions that hold therapeutic promise. Among these newer promising treatments, we include, optogenetic, pharmacological, and extinction-based approaches, as well as lifestyle modifications, with combinatorial treatment regimens of these holding the most promise.

► We highlight new therapies for fear and anxiety from the connectome to epigenome. ► Optogenetic approaches will potentially be useful to treat fear and anxiety. ► Drugs that modify the epigenetic landscape hold therapeutic promise. ► Lifestyle interventions (e.g. diet, exercise, meditation) should be considered. ► Combinatorial approaches hold the most promise to alleviate fear and anxiety.