parents owned their own home when she was born, an indicator of childhood socioeconomic status (data not shown). Analyses restricted to women with no missing MHI-5 or CCI responses showed similar results. Although there were too few premenopausal women to analyze this group separately, analyses restricted to postmenopausal women consistently on HRT between menopause and bone lead mea- surement (n = 97) were similar to analyses that also included women who were premenopausal (data not shown). Among women who were premenopausal and postmenopausal women who were consistently on HRT, analyses of dichotomized outcomes also yielded similar results when we included as “cases” women tak- ing antidepressant or antianxiety medication— regardless of their MHI-5 or CCI score—along with women who were cases based on their symptom scores (data not shown). Discussion We found increased depressive symptom scores and high phobic anxiety scores in asso- ciation with increasing tibia, but not patella, bone lead concentration among women who were either premenopausal or postmenopausal and consistently on HRT between meno- pause and bone lead measurement. These associations were independent of age, educa- tion, husband’s education, cigarette smok- ing, alcohol intake, and employment status. These results were observed among women with low blood lead concentrations consistent with nonoccupational background popula- tion exposures and presumed relatively low cumulative exposures (Table 1). The geomet- ric mean blood lead concentration among our women was 2.37 μg/dL, which is similar to levels seen among women of comparable age in NHANES data from the same time periods (Jackson et al. 2010; Pirkle et al. 1998). That the association was seen among pre- menopausal and postmenopausal women on HRT, rather than among the full sample, Cumulative lead exposure and depression and anxiety could be the result of less bone loss in these women compared with postmenopausal women who did not consistently take HRT (Nelson et al. 2002). Specifically, associa- tions may have been attenuated for all women combined if tibia bone lead levels were a less accurate marker of cumulative lead exposure in postmenopausal women that were not tak- ing HRT, a possible result of measurement error resulting from variation in the degree of bone turnover among these women. A bio- logical interaction between HRT and lead that results in greater effects among HRT users is an alternative possibility. That the results are due to chance in this subgroup also can- not be ruled out. We observed an unexpected inverse association between patella lead and anxiety symptoms among women who were premenopausal or postmenopausal on HRT, although this was likely driven by a small number of women with high patella lead con- centrations [see Table 3; see also Supplemental Material, Table 2 (http://dx.doi.org/10.1289/ ehp.1104395)]. There was also some sug- gestion of less MHI-5 depressive symptoms with higher patella lead in one of the suba- nalyses (see Supplemental Material, Table 1), although this did not reach statistical signifi- cance. Although we cannot dismiss the pos- sibility that these associations are causal, they may also have arisen by chance. Otherwise, patella lead measures were generally not asso- ciated with MHI-5 or CCI reported symp- toms (Tables 2 and 3). The lack of consistent findings with patella lead suggests that the rel- evant lead exposure window for depression or anxiety symptoms may be more long term and therefore better reflected by tibia lead, which has a longer half-life than patella lead. On the other hand, greater variability of patella lead measurements could also contribute to the predominantly patella findings. Limitations of this study include the possibility that our findings are driven by reverse causality. For example, given that phobic anxiety generally has onset at young ages (Kessler et al. 2005), early-life anxiety could affect socioeconomic position, smoking habits, or other risk factors for lead exposure and thereby increase later bone lead levels. Furthermore, it is possible that lower socio- economic status earlier in life could indepen- dently predict both later lead exposure and later phobic anxiety (or possibly depression), Table 3. Adjusteda ORs and 95% CI of high phobic anxiety (CCI ≥ 4) by bone lead tertile. All women (n = 599; 1,100 assessmentsb) Premenopausal or postmenopausal on HRTc (n = 140; 261 assessments) Lead biomarkers CCI ≥ 4 (yes/no) OR (95% CI) CCI ≥ 4 (yes/no) OR (95% CI) Tibia lead tertile (μg/g) < 7.0 78/288 Reference 11/73 Reference 7.0–11.5 66/265 0.84 (0.54, 1.32) 21/83 1.52 (0.60, 3.82) > 11.5 100/303 1.10 (0.73, 1.64) 20/53 2.79 (1.02, 7.59) p-Trend 0.62 0.05 Patella lead tertile (μg/g) < 8.5 80/270 Reference 16/71 Reference 8.5–14.5 78/254 0.96 (0.63, 1.47) 26/64 1.16 (0.41, 3.28) > 14.5 86/330 0.75 (0.49, 1.16) 10/74 0.23 (0.07, 0.69) p-Trend 0.17 0.003 aAdjusted for substudy group, age at bone lead and at CCI measurement, education, husband’s education, alcohol consumption, pack-years of smoking, and employment status at CCI measurement. bOnly 1,098 for patella lead analyses because of missing patella lead data. cWomen who were either premenopausal at the time of bone lead measurement (n = 45) or consistently on HRT between menopause and bone lead measurement (n = 97). Table 2. Adjusteda differences in MHI-5 score by bone lead tertile. All women Premenopausal or postmenopausal on HRTb MHI-5 MHI-5 n (participants/MHI-5 n (participants/MHI-5 Lead biomarker assessments) Score (mean ± SD) Point difference (95% CI) assessments) Score (mean ± SD) Point difference (95% CI) Tibia lead tertile (μg/g) < 7.0 202/558 81 ± 12 Reference 46/129 83 ± 10 Reference 7.0–11.5 159/440 79 ± 13 –1.70 (–3.75, 0.34) 48/134 78 ± 15 –4.31 (–7.88, –0.74) > 11.5 242/672 80 ± 13 –1.06 (–3.05, 0.94) 47/126 76 ± 13 –7.78 (–11.73, –3.83) p-Trend 0.33 0.0001 Total 603/1,670 80 ± 13 141/389 79 ± 13 Patella lead tertile (μg/g) < 8.5 193/532 79 ± 12 Reference 47/128 80 ± 13 Reference 8.5–14.5 179/501 80 ± 13 1.02 (–1.06, 3.11) 49/135 78 ± 14 –0.66 (–5.00, 3.67) > 14.5 230/634 80 ± 13 0.61 (–1.55, 2.78) 45/126 79 ± 12 0.51 (–3.91, 4.94) p-Trend 0.64 0.77 Total 602/1,667 80 ± 13 141/389 79 ± 13 aAdjusted for substudy group, age at bone lead and at MHI-5 measurement, education, husband’s education, alcohol consumption, pack-years of smoking, and employment status at MHI-5 measurement; lower scores indicate more depressive symptoms (lower MHI-5 scores indicate worse symptoms). bWomen who were either premenopausal at the time of bone lead measurement (n = 45) or consistently on HRT between menopause and bone lead measurement (n = 97). Environmental Health Perspectives • volume 120 | number 6 | June 2012 821