Goals: I desire an academic career as a geriatric psychiatrist using neuroimaging findings to better understand neuroanatomic correlates of treatment outcomes in late-life depression. As a new faculty member at Duke University, I am continuing preliminary research examining imaging correlates of treatment response, but it is time to expand the scope of this research. To do so I will need further training and experience in 1) neuroimaging and 2) research design and methodology. Training Experience: I will receive close assessment and tutoring by local experts, as well as mentorship by renowned investigators from other institutions. I will be involved in the assessment and treatment of depressed older individuals, and participate in the analysis of data from this study. I will also take courses in research design, biostatistics, and neuroimaging to supplement this experience. Project Background: Geriatric depression is associated with disability and low quality of life. Many individuals do not respond completely to current treatment: one reason for this poor response may be injury to connections between the prefrontal cortex and basal ganglia, areas implicated in lesion models and functional imaging studies. Diffusion tensor imaging (DTI) can detect and quantify this injury. Hypotheses: Depressed subjects will exhibit greater DTI abnormalities than controls. Greater DTI abnormalities will also be associated with poorer response to acute treatment. At one-year follow-up, depressed subjects will exhibit greater progression of DTI abnormalities than controls. Greater DTI deterioration will also be associated with greater relapse of depression. Methods: Subjects will participate in an acute, 12-week treatment course of sertraline. Baseline assessments and DTI will be obtained. After the acute phase study, subjects will progress to a longitudinal, treatment algorithm-based study; they will receive repeat imaging at one year. Image analysis will focus on frontal areas implicated in depression, particularly the orbital frontal cortex and the dorsolateral prefrontal cortex. Imaging results will be compared with outcome variables using both traditional statistical methods and also statistical parametric mapping (SPM). Discussion: These findings will better describe the role of neural connectivity and striatofrontal dysfunction in geriatric depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23MH065939-01A1
Application #
6614266
Study Section
Special Emphasis Panel (ZRG1-BBBP-5 (01))
Program Officer
Wynne, Debra K
Project Start
2003-07-01
Project End
2008-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$170,750
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Taylor, W D; Steffens, D C; Ashley-Koch, A et al. (2010) Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men. Mol Psychiatry 15:816-22
Venkatraman, Talaignair N; Krishnan, Ranga R; Steffens, David C et al. (2009) Biochemical abnormalities of the medial temporal lobe and medial prefrontal cortex in late-life depression. Psychiatry Res 172:49-54
Pan, Chih-Chuan; McQuoid, Douglas R; Taylor, Warren D et al. (2009) Association analysis of the COMT/MTHFR genes and geriatric depression: an MRI study of the putamen. Int J Geriatr Psychiatry 24:847-55
Hong, Edmund D; Taylor, Warren D; McQuoid, Douglas R et al. (2009) Influence of the MTHFR C677T polymorphism on magnetic resonance imaging hyperintensity volume and cognition in geriatric depression. Am J Geriatr Psychiatry 17:847-55
Qiu, Anqi; Taylor, Warren D; Zhao, Zheen et al. (2009) APOE related hippocampal shape alteration in geriatric depression. Neuroimage 44:620-6
Jones, Lindsay D; Payne, Martha E; Messer, Denise F et al. (2009) Temporal lobe volume in bipolar disorder: relationship with diagnosis and antipsychotic medication use. J Affect Disord 114:50-7
Taylor, Warren D; Zuchner, Stephan; McQuoid, Douglas R et al. (2008) Social support in older individuals: the role of the BDNF Val66Met polymorphism. Am J Med Genet B Neuropsychiatr Genet 147B:1205-12
Zhao, Zheen; Taylor, Warren D; Styner, Martin et al. (2008) Hippocampus shape analysis and late-life depression. PLoS One 3:e1837
Taylor, Warren D; Kuchibhatla, Maragatha; Payne, Martha E et al. (2008) Frontal white matter anisotropy and antidepressant remission in late-life depression. PLoS One 3:e3267
Taylor, Warren D; Zuchner, Stephan; McQuoid, Douglas R et al. (2008) The brain-derived neurotrophic factor VAL66MET polymorphism and cerebral white matter hyperintensities in late-life depression. Am J Geriatr Psychiatry 16:263-71

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