1996 — 2000 |
Pine, Daniel S |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Physiological Correlates of Anxiety in Children @ Columbia University Health Sciences
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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0.921 |
1997 — 2000 |
Pine, Daniel S |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Fluoxetines Effect On Anxiety and Breathing in Children @ New York State Psychiatric Institute
This is an application for a FIRST Award (R29) with the overall purpose of furthering knowledge of therapeutics for three childhood anxiety disorders: social phobia, separation anxiety, and generalized anxiety disorder. Several consideraitons contribute to the importance of this research. First, as a group, these disorders are exceedingly common and associated with considerable childhood distress. Second, many children and adolescents with these disorders face period s of prolonged impairment, with potential ramifications for adulthood mental health. Third, these childhood disorders are often treated with medication, yet there is lottle empirical basis for this practice. The serotonin re-uptake inhibitors (SSRIs) are often used, given their safety and efficacy in a broad array of adult anziety disorders. As a result, there is a compelling need to evaluate the safety and efficacy of the SSRIs in childhood anxiety disorders. Pilot data from open studies suggest that fluoxetine holds promise as a treatment for childhood social phobia, separation anziety, and generalized anxiety disorders. The primary aim of this study is to follow-up these pilot findings through an eight-week double-blind placebo-controlled random assignment clinical eficacy and safety study of fluoxetine in 100 children and adolescents with either social phobia, separation anxiety, or generalized anxiety disorders. The hypothesis will be tested that fluoxetine is superior to placebo in reducing anxiety symptoms and impairment. Beyond lack of knowledge in therapeutics, there is limited understanding of drug action mechanisms in childhood anziety disorders. Studies in adults show that SSRIs may influence anxiety symptoms through effects on a dysregulated respiratory system. Pilot data suggest that the respiratory system is affected in a group of childhood anxiety disorders much as it is affected in a group of adult anxiety disorders. As in adults with panic disorder, children with either social phobia, separation anxiety, or generalized anxiety disorder exhibit irregular ventilatory patterns while breathing room air and CO2 hyper-sensitivity, manifested as increased ventilation and anxiery, while breathing CO2. In adults, these respiratory abnormalities respond to SSRIs. As a result, an examination of fluoxetine's effect on respiration in childhood anziety disorders may provide important data on drug action mechanisms in children. The secondary aim of this study is to examine thenormalizing effect of fluoxetine on irregular ventilatory patterns, ventilatory hypersensitivity, and the anxiety response to CO2 challenge in children and adolescents with anxiety disorders. The hypothesis will be tested that fluoxetine reduces irregular breathing, ventilatory hypersensitivity to CO2, and the anxiety response to CO2.
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0.928 |
1999 — 2000 |
Pine, Daniel S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ventilatory Physiology in Children At Risk For Anxiety @ New York State Psychiatric Institute
The proposed investigation addresses the biology of risk for anxiety disorders. It derives from important parallel scientific concerns regarding the association between adult and child anxiety disorders, coupled with concerns regarding the mechanisms which underlie this association. The study specifically evolves from findings that link childhood separation anxiety disorder (SAD) and adult panic disorder (PD). These findings include: family studies noting elevated rates of SAD in offspring of adults with PD; longitudinal studies linking childhood SAD to adult PD; and biological studies finding CO2-hypersensitivity in children with SAD. CO2-hypersensitivity is also found in both adults with PD and non-ill adult relatives of patients with PD. Taken together, these findings point to the existence of a latent vulnerability to PD reflected in the respiratory system. We propose to examine respiratory function in children at high risk for panic disorder. Major hypotheses are that at risk children, compared to controls, exhibit more variable respiration and hypersensitivity to CO2 exposure as manifested by greater symptomatic and physiologic responses to the inhalation of 5 percent of CO2. We hypothesize that such abnormalities will occur among offspring even in the absence of an anxiety disorder. Aims are addressed through the study of ventilatory measures in offspring, ages nine-to-17, of adults with PD, as compared to offspring of adults with a) social phobia but not panic disorder, b) major depression but neither panic disorder nor social phobia, and c) no mental disorder. A total of nearly 350 children and their parents have been systematically assessed in an ongoing diagnostic study of children at high-risk for anxiety. In the proposed work, diagnosis will be updated with separate interviewers for each family member. Children will undergo a CO2 inhalation procedure in their home with a validated apparatus. Outcome measures consist of: i) pre-experimental respiratory variability, as well as ii) the symptomatic, and iii) physiological response to CO2. A series of studies conducted by the investigative team finds that these factors distinguish adults with PD and children with SAD from relevant contrast groups. Respiratory variables will be rated blind to parental and child diagnosis. The inclusion of offspring from pathological comparison groups, together with offspring of normals, provides a rigorous test of hypothesized diagnostic specificity in the relationship between respiratory factors and anxiety in both children and adults. The proposed study follows naturally from the investigative team's prior work and capitalizes on the availability of a well-characterized sample.
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0.928 |