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Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults.

Rawson KS, Dixon D, Nowotny P, Ricci WM, Binder EF, Rodebaugh TL, Wendleton L, Doré P, Lenze EJ - PLoS ONE (2015)

Bottom Line: We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals.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).Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Predicted values for the interaction effect between brain-derived neurotrophic factor (BDNF) and serotonin transporter gene-linked polymorphic region, 5HTTLPR-rs25531. Within hip fracture participants with two 5HTTLPR-rs25531 LA alleles (LA/LA), contrast results for the GEE analysis indicate BDNF Met/Met carriers had significantly higher depressive symptoms than Val/Val carriers (χ2 = 4.37(1), p = .037) and Val/Met carriers (χ2 = 3.86(1), p = .05). Sample sizes are listed below each graph. Abbreviations: MADRS, Montgomery-Asberg Depression Rating Scale; GEE, Generalized estimating equations.
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pone.0120685.g003: Predicted values for the interaction effect between brain-derived neurotrophic factor (BDNF) and serotonin transporter gene-linked polymorphic region, 5HTTLPR-rs25531. Within hip fracture participants with two 5HTTLPR-rs25531 LA alleles (LA/LA), contrast results for the GEE analysis indicate BDNF Met/Met carriers had significantly higher depressive symptoms than Val/Val carriers (χ2 = 4.37(1), p = .037) and Val/Met carriers (χ2 = 3.86(1), p = .05). Sample sizes are listed below each graph. Abbreviations: MADRS, Montgomery-Asberg Depression Rating Scale; GEE, Generalized estimating equations.

Mentions: Table 2 also summarizes the significant interaction between BDNF and 5HTTLPR-rs25531. As displayed in Fig. 3, Met/Met carriers had significantly higher MADRS scores than Val/Val carriers among participants with two LA alleles, whereas this distinction was not observed among S′ carriers. The interaction remained significant after including time and antidepressant use (p = .014; S1 Table).


Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults.

Rawson KS, Dixon D, Nowotny P, Ricci WM, Binder EF, Rodebaugh TL, Wendleton L, Doré P, Lenze EJ - PLoS ONE (2015)

Predicted values for the interaction effect between brain-derived neurotrophic factor (BDNF) and serotonin transporter gene-linked polymorphic region, 5HTTLPR-rs25531. Within hip fracture participants with two 5HTTLPR-rs25531 LA alleles (LA/LA), contrast results for the GEE analysis indicate BDNF Met/Met carriers had significantly higher depressive symptoms than Val/Val carriers (χ2 = 4.37(1), p = .037) and Val/Met carriers (χ2 = 3.86(1), p = .05). Sample sizes are listed below each graph. Abbreviations: MADRS, Montgomery-Asberg Depression Rating Scale; GEE, Generalized estimating equations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363147&req=5

pone.0120685.g003: Predicted values for the interaction effect between brain-derived neurotrophic factor (BDNF) and serotonin transporter gene-linked polymorphic region, 5HTTLPR-rs25531. Within hip fracture participants with two 5HTTLPR-rs25531 LA alleles (LA/LA), contrast results for the GEE analysis indicate BDNF Met/Met carriers had significantly higher depressive symptoms than Val/Val carriers (χ2 = 4.37(1), p = .037) and Val/Met carriers (χ2 = 3.86(1), p = .05). Sample sizes are listed below each graph. Abbreviations: MADRS, Montgomery-Asberg Depression Rating Scale; GEE, Generalized estimating equations.
Mentions: Table 2 also summarizes the significant interaction between BDNF and 5HTTLPR-rs25531. As displayed in Fig. 3, Met/Met carriers had significantly higher MADRS scores than Val/Val carriers among participants with two LA alleles, whereas this distinction was not observed among S′ carriers. The interaction remained significant after including time and antidepressant use (p = .014; S1 Table).

Bottom Line: We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals.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).Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus