Pain severity as a mediator of the association between depressive symptoms and physical performance in knee osteoarthritis.

OBJECTIVE: Depressive symptoms in knee osteoarthritis (OA) are associated with increased pain severity and declines in physical performance. This study examined whether pain severity mediates the association between depressive symptoms and physical performance in persons with radiographic knee OA. METHOD: Three years of annual data from participants (n = 1,463) with radiographic knee OA in the Osteoarthritis Initiative (OAI) were analyzed. Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D) scale. Pain severity was evaluated with the Western Ontario and McMaster Universities Arthritis Index. Physical performance was assessed via standardized gait speed. Marginal structural models were used to assess the direct (unmediated) effects of depressive symptoms on physical performance and indirect (mediated) effects through pain severity. RESULTS: Direct and indirect effects for a difference in CES-D score of 0-1 were -0.0051 (95% confidence intervals (CI): -0.0053, -0.0049) and -0.0016 (95% CI: -0.0024, -0.0007) standard deviations in gait speed, respectively. Higher depressive symptom severity exhibited diminishing, incremental, direct and indirect effects and for a difference in CES-D score of 15-16 were -0.0045 (95% CI: -0.0047, -0.0042) and -0.0009 (95% CI: -0.0014, -0.0004) standard deviations in gait speed, respectively. Therefore, the magnitude of the mediated, indirect effect, was never larger than 24%. CONCLUSION: Pain severity mediated approximately one-fifth of the association between depressive symptoms and physical performance in persons with radiographic knee OA, and the diminishing incremental effects may explain why unimodal treatment strategies with a single disease target are often ineffective in depressed OA patients.

Bioaccumulation and maternal transfer of PBDE 47 in the marine medaka (Oryzias melastigma) following dietary exposure.

The bioaccumulation and maternal transfer of 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) were investigated in the marine medaka (Oryzias melastigma) following dietary exposure, in which PBDE 47 was bioencapsulated into brine shrimp (Artemia sp.) and fed daily to male-female pairs of medaka. In the accumulation experiment, each 2-month-old (pre-breeding) medaka were provided with dietary PBDE 47 at 1.3±0.2 µg/day for 21 days. Growth-corrected concentrations of PBDE 47 in the medaka increased over the 21 days of exposure and there were no significant differences between males and females at any of the sampling times. Final concentrations were similar for males and females after 21 days (230±30 and 250±30 µgg(-1) wet weight, respectively), accounting for 84-100% of the PBDE 47 provided in the diet. In the maternal transfer experiment, 3-month-old (breeding) medaka were provided with dietary PBDE 47 at 1.2±0.2 µg/day for 18 days, and reached body concentrations of 76±3 (males) and 61±6 (females)µgg(-1) wet weight. Female growth-corrected PBDE 47 concentrations were significantly lower than males by day 12 (P<0.05), and egg PBDE 47 concentrations were up to 25 ng/egg by day 18. Our results showed that maternal transfer is an important offloading mechanism for female fish. The fact that lipid normalized egg:female PBDE ratios did not significantly deviate from 1 further indicated that the maternal transfer of PBDE 47 is associated with lipid mobilization during egg production.