Neurobiology of Early-onset Anxiety Disorders

The past two decades of research on both the longitudinal course and familial distribution of anxiety disorders suggest that many forms of adult anxiety disorders can be conceptualized as developmental conditions. Family studies demonstrate strong associations between anxiety in parents and children (Battaglia et al. 1998 ; Weissman et al. 1997 ). Similarly, prospective epidemiological studies fi nd strong associations between anxiety during adolescence and anxiety, as well as major depression, during adulthood (Pine 1999 ). Given the lifelong implications of anxiety disorders in childhood and adolescence, it is critical to understand the basic neurobiological mechanisms involved in these disorders early in their developmental trajectory. Clinical characteristics of childhood anxiety disorders have made them particularly challenging to study, highlighting the importance of using neurobiological markers to eventually improve the nosological system and to develop targeted interventions. For example, childhood anxiety disorders exhibit high rates of comorbidity in both communityand clinic-based studies (Gurley et al. 1996; Verduin & Kendall 2003 ). Comorbidity appears particularly high for generalized anxiety disorder (GAD) in children, which shows strong associations with a range of conditions, including social anxiety disorder (SAD) and major depression (Kessler & Walters 1998 ; Pine 1999 ). Such high rates of comorbidity raise questions as to the validity of current nosological categories and suggest the need for alternative bodies of knowledge to validate conditions (Pine 2007 ). Additionally, there is an apparent contradiction between the transient nature of some childhood anxiety disorders and evidence suggesting that adult mood and anxiety disorders often begin in childhood. Longitudinal data suggest that this paradox may result from very high rates of childhood anxiety disorders. In most children, these disorders remit. However, those children who remain anxious may account for a large proportion of adult cases of both mood and anxiety disorders. Given this possibility, there is a pressing need to determine factors that distinguish anxious children at low versus high risk for continued anxiety or depression in adulthood. With advances in neurobiological understandings, new avenues for developing such insights are available. Specifi cally, children and adolescents who manifest clinically signifi cant anxiety but then mature to become adults free of such anxiety might be viewed as having successfully extinguished their fears. Anxious children and adolescents who remain anxious as adults can be viewed as suffering from a defi ciency in extinction (Pine et al. 2009 ). Monumental increases have occurred in understandings of fear extinction neurobiology. As such, the view of persistently anxious children as suffering from some form of “extinction defi cit” generates novel insights for treatments that target anxiety by attempting to facilitate extinction. The current chapter reviews the progress that has been made in the development of neurobiological models of pediatric anxiety disorders, as well as ongoing efforts to bridge basic science and clinical research. The fi rst section briefl y reviews the clinical characteristics of pediatric anxiety disorders. Post-traumatic stress disorder and obsessive-compulsive disorder will not be covered in the present chapter and can be found in Chapters X and Y. The second section reviews the basic science research of the neurobiology of fear responses that has provided the foundation for studies of youth with clinical anxiety. The third section will survey clinical research on the neurobiology of anxiety disorders in children and adolescents. Specifi c physiological responses associated with fear and panic, as well as genetic infl uences on clinical symptoms associated with anxiety disorders, will also be presented. The concluding section presents future directions for research on