Disabling medical events are a major risk factor for late-life depression (LID), which in turn leads to poor functional recovery and increased mortality. Effective prevention of LLD in this setting requires research on its etiology and risk factors. Thus, we will examine genetic polymorphisms in the serotonergic system, and psychological, social, and aging-related factors as risk factors for the onset of LLD after a hip fracture, a severe and disabling event. In our pilot work, the serotonin transporter promoter polymorphism (5-HTTLPR) s allele and the 5-HT2a (-1438)A/G allele were associated with an increased likelihood of LLD and/or higher levels of depressive symptoms after hip fracture. This grant integrates clinical research methods for assessing LLD with state of the art genetic methods. We will examine association of five genetic polymorphisms in the serotonin system (5-HTTLPR, 5-HT2a (-1438)A/G, 5-HT1a (-1019)C/G, TPH-2 (1463)G/A and BDNF dinucleotide repeat) with the onset and course of LLD in 470 elderly persons who have had a hip fracture. We will collect samples for genotyping, and we will follow subjects for one year. We will longitudinally assess LLD as well as variables related to vulnerability to LLD (e.g., cognitive status, disability, medical and psychiatric comorbidity, medication use, and life events). We will collect the same information over one year on a comparison group of 100 elderly persons who have not suffered a hip fracture. We hypothesize that these polymorphisms will be associated with LLD in the hip fracture group. Beyond the testing of study hypotheses, we will model risk for LLD using both genetic and non-genetic factors (e.g., vulnerability due to personality, disposition, or prior depression;age-related changes;social support). We will replicate genetic results in a second sample of hip fracture subjects. Data and samples from this study will be made available for future genetic studies, by our group as well as other investigators. The public health relevance is great, as LLD is a devastating and difficult-to-treat illness. The proposed research will be essential to reducing the burden of LLD by improving our understanding of the etiology of this illness: additionally, findings from this research could lead risk profiling using genetic and other risk factors, a necessary step for prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH074596-03
Application #
7585773
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Evans, Jovier D
Project Start
2007-03-01
Project End
2012-02-29
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
3
Fiscal Year
2009
Total Cost
$362,561
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Oughli, Hanadi Ajam; Chen, Gengsheng; Philip Miller, J et al. (2018) Cognitive Improvement in Older Adults in the Year After Hip Fracture: Implications for Brain Resilience in Advanced Aging. Am J Geriatr Psychiatry 26:1119-1127
Kornfield, Sara L; Lenze, Eric J; Rawson, Kerri S (2017) Predictors of Posttraumatic Stress Symptoms and Association with Fear of Falling After Hip Fracture. J Am Geriatr Soc 65:1251-1257
Iaboni, Andrea; Rawson, Kerri; Burkett, Craig et al. (2017) Potentially Inappropriate Medications and the Time to Full Functional Recovery After Hip Fracture. Drugs Aging 34:723-728
Cristancho, P; Lenze, E J; Avidan, M S et al. (2016) Trajectories of depressive symptoms after hip fracture. Psychol Med 46:1413-25
Bower, Emily S; Wetherell, Julie Loebach; Petkus, Andrew J et al. (2016) Fear of Falling after Hip Fracture: Prevalence, Course, and Relationship with One-Year Functional Recovery. Am J Geriatr Psychiatry 24:1228-1236
Langer, Julia K; Weisman, Jaclyn S; Rodebaugh, Thomas L et al. (2015) Short-term affective recovery from hip fracture prospectively predicts depression and physical functioning. Health Psychol 34:30-9
Bower, Emily S; Wetherell, Julie Loebach; Merz, C Caroline et al. (2015) A new measure of fear of falling: psychometric properties of the fear of falling questionnaire revised (FFQ-R). Int Psychogeriatr 27:1121-33
Rawson, Kerri S; Dixon, David; Nowotny, Petra et al. (2015) Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults. PLoS One 10:e0120685
Lenze, Eric J; Goate, Alison M; Nowotny, Petra et al. (2010) Relation of serotonin transporter genetic variation to efficacy of escitalopram for generalized anxiety disorder in older adults. J Clin Psychopharmacol 30:672-7
Talkowski, Jaime B; Lenze, Eric J; Munin, Michael C et al. (2009) Patient participation and physical activity during rehabilitation and future functional outcomes in patients after hip fracture. Arch Phys Med Rehabil 90:618-22

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