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Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders
Mazen A Kheirbek13, Kristen C Klemenhagen4, Amar Sahay58 & Ren Hen13,9
Although an influence of adult neurogenesis in mediating some of the effects of antidepressants has received considerable attention in recent years, much less is known about how alterations in this form of plasticity may contribute to psychiatric disorders such as anxiety and depression. One way to begin to address this question is to link the functions of adult-born hippocampal neurons with specific endophenotypes of these disorders. Recent studies have implicated adult-born hippocampal neurons in pattern separation, a process by which similar experiences or events are transformed into discrete, non-overlapping representations. Here we propose that impaired pattern separation underlies the overgeneralization often seen in anxiety disorders, specifically post-traumatic stress disorder and panic disorder, and therefore represents an endophenotype for these disorders. The development of new, pro-neurogenic compounds may therefore have therapeutic potential for patients who display pattern separation deficits.
npg 2012 Nature America, Inc. All rights reserved.
Anxiety disorders have a lifetime prevalence of over 25%1, making them the most common of psychiatric disorders. They account for more than 30% of the United Statess total expenditure on mental illness, costing the country an estimated $45 billion annually. Moreover, anxiety disorders are often chronic conditions that severely affect quality of life and work productivity and, in the common situation in which they begin early in life (for example, by adolescence), they substantially disrupt personal and social development2. Developing novel and effective therapeutics for improving outcome in these disorders will therefore be a major benefit to society.
Panic disorder has a lifetime prevalence of 24% and is characterized by recurrent unexpected panic attacks with intense physical symptoms and persistent fear of future attacks. Persons with panic disorder often avoid situations (for example, public transportation) that they have come to associate with panic attacks. Post-traumatic stress disorder (PTSD), which has a lifetime prevalence of 58%, is an anxiety disorder that can occur after a severely traumatic event. The disorder is characterized by re-experiencing the trauma through intrusive thoughts; memories and nightmares; autonomic hyperarousal symptoms and avoidance of reminders of the trauma, with
certain reminders often gaining heightened salience for...