title: Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults.
abstract: 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.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Kerri S
authors.initials: KS
authors.lastname: Rawson
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Dixon
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Petra
authors.initials: P
authors.lastname: Nowotny
authors.affiliation: Orthopaedic Trauma Service, Washington University School of Medicine / Barnes-Jewish Hospital, Saint Louis, Missouri, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Ricci
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Ellen F
authors.initials: EF
authors.lastname: Binder
authors.affiliation: Department of Psychology, Washington University in Saint Louis, Saint Louis, Missouri, United States of America.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rodebaugh
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Leah
authors.initials: L
authors.lastname: Wendleton
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Doré
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
mesh_terms: D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D003863:Depression / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D005260:Female; D005838:Genotype; D006620:Hip Fractures / Q000378:metabolism / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin