Association of serotonin-1A and 2A receptor promoter polymorphisms with depressive symptoms and functional recovery in elderly persons after hip fracture

Background: Depression is common after hip fracture and is associated with poorer functional recovery. Polymorphisms of the serotonin 1a (5HTR1A) and 2a receptors (5HTR2A) are associated with depression; therefore, we examined their association with depressive symptoms and functional recovery after hip fracture. Methods: 145 elderly women were followed for 12 months after hip fracture. Depressive symptoms were measured with the 15-item Geriatric Depression Scale (GDS). Functional status was measured by Lower Extremity Physical and Instrumental Activity of Daily Living scales (LPADLs and IADLs). Time-adjusted general linear regression models compared mean GDS between those with and without risk alleles for 5HTR1A and 5HTR2A. Results: Women with 1-2 copies of the 5HTR1A (- 1019) G allele had higher GDS scores (Adjusted Mean Difference = 0.59; 95% CI, 0.12-1.06), and poorer IADL scores (Adjusted Mean Difference = 0.24; 95%CI - 0.002 to 0.49), compared to those without this allele, controlling for potential confounders and 5HTR2A. Depressive symptoms partly accounted for poorer IADL recovery. Women with 1-2 copies of the 5HTR2A (- 1438) C allele did not have significantly higher GDS scores (Adjusted Mean Difference = 0.34; 95%CI, - 0.20 to 0.87) and had better IADL scores (Adjusted Mean Difference = - 0.40; 95%CI - 0.74 to 0.06) than those with A/A genotype. Limitations: The findings are limited by small sample size and the use of a screening scale to measure depression. Conclusions: The 5HTR1A (- 1019) G allele is associated with increased depressive symptoms after hip fracture, which in turn accounts for poorer functional recovery. These results suggest a role for serotonergic genetic variation in elderly persons' resilience and recovery from medical events.