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.

Fear of Falling after Hip Fracture: Prevalence, Course, and Relationship with One-Year Functional Recovery

“…Participants in the parent study were recruited within one week of hip fracture from eight hospitals in the St. Louis, MO area between 2008-2012 (19, 20). All patients who were 60 years or older and had a primary diagnosis of hip fracture to be surgically repaired were consecutively screened.…”

“…The MADRS was assessed by trained raters. Test-retest reliability was ICC = .84, CI = 0.51-0.95 (19). …”

“…The current study used data from a prospective, longitudinal study of participants with hip fracture (19, 20). The primary aim of the parent study was to examine genetic influences in the development of depression following a major medical event (i.e., hip fracture).…”

Regenerative Properties of Fetal n. Raphe Cells in Modeling Injuries of Serotonergic Neurite-Glial Fibers in Vitro

“…Enrichment of fetal n. raphe neuronal cells by serotonin producing cells under the effect of differentiating factors [9,10] was confirmed by histochemical and immunoenzyme methods, as well as by study the expression of relevant regulatory genes of serotogenesis. So, the content of serotonergic neurons in suspension culture of n. raphe cell population was increased by 1.6 times (Table 1), and serotonin content-by 1.7 times ( Table 1).…”

“…Culturing was conducted on DMEM (PAA, Austria) with the addition of 10% normal FCS (PAA, Austria) for the next week. The addition of BDNF, 50 ng/mL (Sigma, USA) stimulated cell serogenesis [9,10]. Medium replacement was performed in 3-4 days.…”