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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

Observed Montgomery-Asberg Depression Rating Scale (MADRS) scores over time for participants with hip fracture and healthy comparisons.The number of participants with hip fracture and healthy comparisons are listed below the figure.
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pone.0120685.g001: Observed Montgomery-Asberg Depression Rating Scale (MADRS) scores over time for participants with hip fracture and healthy comparisons.The number of participants with hip fracture and healthy comparisons are listed below the figure.

Mentions: Our time course data shows hip fracture to be depressogenic from week 1 to 4, followed by a decline in depressive symptoms (Fig. 1). Therefore, to examine the candidate polymorphisms, we focused on the four-week period post-fracture where an increase in depressive scores among participants with hip fracture was observed relative to comparisons.


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)

Observed Montgomery-Asberg Depression Rating Scale (MADRS) scores over time for participants with hip fracture and healthy comparisons.The number of participants with hip fracture and healthy comparisons are listed below the figure.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120685.g001: Observed Montgomery-Asberg Depression Rating Scale (MADRS) scores over time for participants with hip fracture and healthy comparisons.The number of participants with hip fracture and healthy comparisons are listed below the figure.
Mentions: Our time course data shows hip fracture to be depressogenic from week 1 to 4, followed by a decline in depressive symptoms (Fig. 1). Therefore, to examine the candidate polymorphisms, we focused on the four-week period post-fracture where an increase in depressive scores among participants with hip fracture was observed relative to comparisons.

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