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

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. 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. 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. The findings are limited by small sample size and the use of a screening scale to measure depression. 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.