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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

Mediation model using Hayes’ (2013) multicategorical independent variable method. Mediation test of the relationship between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and the Functional Recovery Score (FRS) at week 12 as a result of the Montgomery-Asberg Depression Rating Scale (MADRS) depression scores. Results are shown for the BDNF Val+:Met/Met contrast. The Val/Val:Val/Met contrast was not significant.
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pone.0120685.g004: Mediation model using Hayes’ (2013) multicategorical independent variable method. Mediation test of the relationship between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and the Functional Recovery Score (FRS) at week 12 as a result of the Montgomery-Asberg Depression Rating Scale (MADRS) depression scores. Results are shown for the BDNF Val+:Met/Met contrast. The Val/Val:Val/Met contrast was not significant.

Mentions: The indirect effects from the mediation analysis were significant and indicated BDNF genotype affects functional recovery as a result of depressive symptoms at weeks 12, 26, and 52 (S3 Table). Total, direct, and indirect effects for the Val+:Met/Met contrast at week 12 are provided in Fig. 4 for illustration. The total effect indicated Val+ carriers had significantly better FRS than Met/Met carriers at week 12. The direct effects indicated Val+ carriers had significantly lower MADRS scores relative to Met/Met carriers and participants with lower MADRS scores had higher FRS, regardless of BDNF genotype, at all 3 time points. Indirect effects indicated MADRS scores are a significant mediator for the Val+:Met/Met contrast. That is, Val+ carriers scored an average 1.728 units higher on FRS at week 12 relative to Met/Met carriers due to the effect of BDNF genotype on depressive symptoms. Similar results were seen using FRS as the outcome at week 26 and 52. Neither total, direct, nor indirect effects for the Val/Val:Val/Met contrast were significant. There was no evidence that BDNF genotype influenced FRS independent of its effect on depressive symptoms at week 12, 26, or 52 for either contrast.


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)

Mediation model using Hayes’ (2013) multicategorical independent variable method. Mediation test of the relationship between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and the Functional Recovery Score (FRS) at week 12 as a result of the Montgomery-Asberg Depression Rating Scale (MADRS) depression scores. Results are shown for the BDNF Val+:Met/Met contrast. The Val/Val:Val/Met contrast was not significant.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120685.g004: Mediation model using Hayes’ (2013) multicategorical independent variable method. Mediation test of the relationship between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and the Functional Recovery Score (FRS) at week 12 as a result of the Montgomery-Asberg Depression Rating Scale (MADRS) depression scores. Results are shown for the BDNF Val+:Met/Met contrast. The Val/Val:Val/Met contrast was not significant.
Mentions: The indirect effects from the mediation analysis were significant and indicated BDNF genotype affects functional recovery as a result of depressive symptoms at weeks 12, 26, and 52 (S3 Table). Total, direct, and indirect effects for the Val+:Met/Met contrast at week 12 are provided in Fig. 4 for illustration. The total effect indicated Val+ carriers had significantly better FRS than Met/Met carriers at week 12. The direct effects indicated Val+ carriers had significantly lower MADRS scores relative to Met/Met carriers and participants with lower MADRS scores had higher FRS, regardless of BDNF genotype, at all 3 time points. Indirect effects indicated MADRS scores are a significant mediator for the Val+:Met/Met contrast. That is, Val+ carriers scored an average 1.728 units higher on FRS at week 12 relative to Met/Met carriers due to the effect of BDNF genotype on depressive symptoms. Similar results were seen using FRS as the outcome at week 26 and 52. Neither total, direct, nor indirect effects for the Val/Val:Val/Met contrast were significant. There was no evidence that BDNF genotype influenced FRS independent of its effect on depressive symptoms at week 12, 26, or 52 for either contrast.

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