PMID- 25781924 OWN - NLM STAT- MEDLINE DCOM- 20160204 LR - 20201217 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults. PG - e0120685 LID - 10.1371/journal.pone.0120685 [doi] LID - e0120685 AB - Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val) to methionine (Met) polymorphism in brain-derived neurotrophic factor (BDNF), serotonin 1A receptor (5HT1a-rs6295) polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR) interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531) as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012). BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37). Unlike prior studies of stressful life events, the S' 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006). No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor. FAU - Rawson, Kerri S AU - Rawson KS AD - Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Dixon, David AU - Dixon D AD - Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Nowotny, Petra AU - Nowotny P AD - Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Ricci, William M AU - Ricci WM AD - Orthopaedic Trauma Service, Washington University School of Medicine / Barnes-Jewish Hospital, Saint Louis, Missouri, United States of America. FAU - Binder, Ellen F AU - Binder EF AD - Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Rodebaugh, Thomas L AU - Rodebaugh TL AD - Department of Psychology, Washington University in Saint Louis, Saint Louis, Missouri, United States of America. FAU - Wendleton, Leah AU - Wendleton L AD - Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Dore, Peter AU - Dore P AD - Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America. FAU - Lenze, Eric J AU - Lenze EJ AD - Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America. LA - eng GR - T32 MH014677-36/MH/NIMH NIH HHS/United States GR - UL1TR000448/TR/NCATS NIH HHS/United States GR - UL1 TR000448/TR/NCATS NIH HHS/United States GR - T32 MH014677/MH/NIMH NIH HHS/United States GR - R01 MH074596/MH/NIMH NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural DEP - 20150317 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (SLC6A4 protein, human) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 112692-38-3 (Receptor, Serotonin, 5-HT1A) RN - 333DO1RDJY (Serotonin) SB - IM EIN - PLoS One. 2015;10(4):e0126451. PMID: 25886268 MH - Adult MH - Aged MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Depression/*genetics/metabolism/psychology MH - Female MH - Genotype MH - Hip Fractures/metabolism/psychology MH - Humans MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Receptor, Serotonin, 5-HT1A/genetics/metabolism MH - Serotonin/genetics/metabolism MH - Serotonin Plasma Membrane Transport Proteins/*genetics/metabolism MH - Stress, Psychological/*genetics/metabolism PMC - PMC4363147 COIS- Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing intrests: EJL receives grant support from Roche and Lundbeck. WMR receives royalties from Smith&Nephew, Biomet (expected), Stryker (expected), and Lippincott (expected), and is a consultant for Smith&Nephew, Biomet, and Styker, receives income from Journal of Bone and Joint Surgery, and receives research and institutional support from Smith&Nephew. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. EDAT- 2015/03/18 06:00 MHDA- 2016/02/05 06:00 PMCR- 2015/03/17 CRDT- 2015/03/18 06:00 PHST- 2014/08/21 00:00 [received] PHST- 2015/01/25 00:00 [accepted] PHST- 2015/03/18 06:00 [entrez] PHST- 2015/03/18 06:00 [pubmed] PHST- 2016/02/05 06:00 [medline] PHST- 2015/03/17 00:00 [pmc-release] AID - PONE-D-14-37107 [pii] AID - 10.1371/journal.pone.0120685 [doi] PST - epublish SO - PLoS One. 2015 Mar 17;10(3):e0120685. doi: 10.1371/journal.pone.0120685. eCollection 2015.