The purpose of the current K23 application is to provide support for the candidate's development into a highly productive independent clinical investigator in the pathogenesis of depression. A comprehensive five-year career development and research plan will be undertaken with the mentorship of Dr. Lawrence H. Price, an established senior scientist with internationally recognized expertise in neurobiological investigations of depression and extensive experience mentoring junior faculty. In addition, a team of comentors and consultants has been assembled to provide expert guidance in the training and research components of the proposed award. The Career Development Plan has been carefully designed to provide in-depth training in the following domains: the neurobiology of depression and the hypothalamic-pituitary-adrenal (HPA) axis, the role of stress and adversity in the pathogenesis of depression, the neuropsychology of depression and neuroendocrine function, and research ethics and methodology. In addition, further training in longitudinal methodology will be undertaken in preparation for a prospective, longitudinal R01 submission in Year 4-5 of the award. Formal training in these areas will be obtained through a curriculum of intramural and extramural didactics and coursework, preceptorships, research, research group meetings, and participation in national research meetings. The proposed research plan involves an examination of stress hormone responses to neuroendocrine challenge tests in relation to family history of depression and history of childhood adversity. Secondly, associations between HPA dysregulation and cognitive functioning will be investigated. This study offers the potential for substantial insight into the pathogenesis of depression and the effects of early-life stress and hyperactivity of the HPA axis. Results of this study, in combination with training in the design, implementation, and analysis of longitudinal studies, will comprise the basis of an R01 to be submitted at the beginning of Year 5. This R01 proposal will entail a prospective longitudinal investigation of the effects of childhood adversity and maternal mood and anxiety disorders on the development of neuroendocrine dysfunction and psychopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH067947-05
Application #
7315380
Study Section
Brain Disorders and Clinical Neuroscience 5 (BDCN)
Program Officer
Wynne, Debra K
Project Start
2003-12-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2009-11-30
Support Year
5
Fiscal Year
2008
Total Cost
$180,778
Indirect Cost
Name
Butler Hospital (Providence, RI)
Department
Type
DUNS #
069847804
City
Providence
State
RI
Country
United States
Zip Code
02906
Tyrka, Audrey R; Ridout, Kathryn K; Parade, Stephanie H (2016) Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults. Dev Psychopathol 28:1319-1331
Saczawa, Mary E; Graber, Julia A; Brooks-Gunn, Jeanne et al. (2013) Methodological considerations in use of the cortisol/DHEA(S) ratio in adolescent populations. Psychoneuroendocrinology 38:2815-9
Tyrka, A R; Walters, O C; Price, L H et al. (2012) Altered response to neuroendocrine challenge linked to indices of the metabolic syndrome in healthy adults. Horm Metab Res 44:543-9
Tyrka, Audrey R; Lee, Janet K; Graber, Julia A et al. (2012) Neuroendocrine predictors of emotional and behavioral adjustment in boys: longitudinal follow-up of a community sample. Psychoneuroendocrinology 37:2042-6
Carpenter, Linda L; Shattuck, Thaddeus T; Tyrka, Audrey R et al. (2011) Effect of childhood physical abuse on cortisol stress response. Psychopharmacology (Berl) 214:367-75
Tyrka, Audrey R; Kelly, Megan M; Graber, Julia A et al. (2010) Behavioral adjustment in a community sample of boys: links with basal and stress-induced salivary cortisol concentrations. Psychoneuroendocrinology 35:1167-77
Tyrka, Audrey R; Price, Lawrence H; Kao, Hung-Teh et al. (2010) Childhood maltreatment and telomere shortening: preliminary support for an effect of early stress on cellular aging. Biol Psychiatry 67:531-4
Tyrka, Audrey R; Price, Lawrence H; Gelernter, Joel et al. (2009) Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity. Biol Psychiatry 66:681-5
Tyrka, Audrey R; Wyche, Margaret C; Kelly, Megan M et al. (2009) Childhood maltreatment and adult personality disorder symptoms: influence of maltreatment type. Psychiatry Res 165:281-7
Tyrka, Audrey R; Wier, Lauren; Price, Lawrence H et al. (2008) Childhood parental loss and adult hypothalamic-pituitary-adrenal function. Biol Psychiatry 63:1147-54

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