This is an application for a Scientific Development Award for Clinicians. The broad goal of this proposal is to develop the applicant's ability to conduct independent biological research in clinical and epidemiologic samples of youth. David Shaffer, MD will serve as the preceptor for the grant. He will train the applicant in psychiatric assessment methods while integrating training in other areas. This will include training in biostatistics, under the mentorship of Patricia Cohen, PhD, and training in physiology, through internships under experienced researchers coordinated by Donald Klein, MD. To facilitate an in-depth development of research skills, this grant focuses on examining the biological correlates of childhood anxiety disorders with reference to research in adults. The applicant will be trained in the assessment of three inter-related physiologic systems: the respiratory, cardiac, and autonomic nervous systems. This grant combines hands-on training in the physiology of these systems, as part of the Career Development Plan, with data collection in the Research Plan designed to examine physiologic correlates of childhood anxiety disorders. The presence of comparable biological correlates of anxiety disorders in children and adults would support the validity of childhood diagnoses. While research notes diverse biological correlates of adult anxiety disorders, studies of respiratory, cardiac, and autonomic profiles appear particularly well suited for studies in youth. Adults with anxiety disorders in general, and panic disorder in particular, exhibit abnormalities in response to respiratory challenges with CO2, including chaotic breathing patterns as well as heightened anxiogenesis. Adults with anxiety disorders also exhibit abnormal heart period variability patterns, which suggest impaired autonomic regulation of cardiac activity, and abnormal biologic responses to noradrenergic challenges with clonidine, which suggests abnormal sympathetic function. In the Research Plan for this grant, clinical and epidemiologic samples of youth will receive assessments of respiratory and autonomic function through CO2 challenges and measurement of heart period variability patterns. Clinical samples will receive further assessment of sympathetic functions via clonidine challenges. A comparison sample of depressed youth will be studied to compare biological correlates of anxiety and depressive disorders. Finally, samples will be followed prospectively to determine whether biological correlates of childhood anxiety disorders can predict short term course.
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| Pine, Daniel S; Cohen, Patricia; Johnson, Jeffrey G et al. (2002) Adolescent life events as predictors of adult depression. J Affect Disord 68:49-57 |
| Kentgen, L M; Tenke, C E; Pine, D S et al. (2000) Electroencephalographic asymmetries in adolescents with major depression: influence of comorbidity with anxiety disorders. J Abnorm Psychol 109:797-802 |
