Eum et al. and anxiety are highly comorbid (Byers et al. lead. Compared with women in the lowest depression symptoms) or at least 60, among 2010; Kessler et al. 1994). In our population, tertile of tibia lead concentration, women in premenopausal women and postmenopausal MHI-5 and CCI assessments were done in the middle and highest tertiles scored 4.31 women consistently on HRT (n = 37 MHI-5 different years of the NHS, and Spearman (95% CI: –7.88, –0.74) and 7.78 (95% CI: assessments < 60), the OR for severe depres- correlations for these two exams, which –11.73, –3.83) points lower, respectively, on sion symptoms for women in the highest ranged from –0.22 to –0.34, were modest. the MHI-5 (Table 2). In sensitivity analyses tertile of tibia lead was 3.71 (95% CI: 1.18, In analyses of all women, depressive either restricting the analyses to MHI-5 assess- 11.64; p-trend = 0.02) compared with women symptoms were inconsistently worse with ments that occurred after bone lead measure- in the lowest tertile. In analyses of all women, higher tibia lead levels (Table 2). Compared ment or restricting to women who scored < 4 the OR for depression for women in the high- with the lowest tertile of tibia lead concen- on both CCI assessments, results were similar est, compared with lowest, tibia tertile was tration, women in the middle tertile scored [see Supplemental Material, Table 1 (http:// 1.42 (95% CI: 0.81, 2.46). These results were 1.70 MHI-5 points worse (95% CI: –3.75, dx.doi.org/10.1289/ehp.1104395)]. similar using the alternative MHI-5 cutoff of 0.34), and those in the highest tertile scored When lead was modeled as a continu- < 53 (Berwick et al. 1991; Holmes 1998), but 1.1 points worse (95% CI: –3.1, 0.94). At the ous variable, there was a 5.63-point reduc- fewer women met this threshold, so confidence time of bone lead measurement, most of the tion (95% CI: –8.49, –2.78) in MHI-5 limits were much larger (data not shown). women (n = 572) were postmenopausal, with score per 1 SD higher tibia lead (9.5 μg/g) A similar pattern was apparent for anxi- a mean ± SD of 12.2 ± 6.5 years since meno- among premenopausal women and post- ety symptoms. Tibia bone lead concentra- pause. In analyses restricted to premenopausal menopausal women consistently on HRT tion was not associated with CCI scores in women and postmenopausal women who [see Supplemental Material, Table 1 (http:// the overall population (Table 3). The stron- were consistently on HRT, MHI-5 scores dx.doi.org/10.1289/ehp.1104395)]. When we gest association appeared in analyses among decreased monotonically with increasing tibia dichotomized MHI-5 scores as < 60 (severe premenopausal and postmenopausal women consistently on HRT. In this subset, the ORs for severe phobic anxiety (CCI ≥ 4) for Table 1. Levels of lead exposure biomarkers (μg/g) by characteristic among women with measures of women in the middle and highest tertiles psychological symptoms (n = 617). of tibia lead concentration, compared with Tibia lead Patella lead those in the lowest tertile, were 1.52 (95% Characteristica n Mean ± SD Median n b Mean ± SD Median CI: 0.60, 3.82) and 2.79 (95% CI: 1.02, Age at lead exposure assessment (years) 7.59; p-trend = 0.05), respectively (Table 3). < 55 95 9.2 ± 7.4 8.7 95 12.8 ± 9.6 11.3 All of these results were similar in sensitiv- 55–59 143 9.2 ± 8.6 9.0 143 10.8 ± 10.0 10.4 ity analyses restricted to the CCI assessments 60–64 194 9.3 ± 9.7 9.0 194 12.1 ± 11.1 13.0 that occurred after bone lead measurement 65–69 142 12.9 ± 10.3 13.0 142 13.1 ± 12.4 12.1 [see Supplemental Material, Table 2 (http:// ≥ 70 43 12.9 ± 11.4 12.2 42 17.3 ± 13.6 16.1 Education in 1992 dx.doi.org/10.1289/ehp.1104395)]. When Registered nurse diploma 351 10.4 ± 9.6 10.0 350 13.3 ± 10.7 12.2 lead was modeled as a continuous variable, Bachelor’s degree 161 10.6 ± 8.8 9.6 161 10.6 ± 12.1 11.3 the OR for high phobic anxiety was 2.06 Master’s or doctorate degree 72 8.6 ± 10.9 8.0 72 12.6 ± 12.1 11.7 (95% CI: 1.01, 4.22) per 1 SD higher tibia Missing 33 12.2 ± 9.6 11.0 33 12.2 ± 10.0 14.0 lead (9.5 gμ/g) among premenopausal women Husband education in 1992 and postmenopausal women consistently on High school or less 144 11.6 ± 10.1 10.7 143 14.2 ± 12.6 13.0 HRT (see Supplemental Material, Table 2). College education 157 10.0 ± 9.3 9.6 157 12.1 ± 11.7 11.3 In general, we found much weaker, incon- Graduate school 168 9.5 ± 10.0 9.0 168 11.8 ± 10.4 11.7 No husband (not married) 70 10.6 ± 8.8 10.0 70 12.2 ± 11.0 12.2 sistent, or associations between patella Missing 78 10.4 ± 8.4 9.3 78 11.7 ± 9.3 12.2 lead concentration and either outcome. Employment status in 2004 However, among premenopausal women Retired/homemaker 305 11.5 ± 10.3 10.4 304 14.0 ± 11.1 13.0 and postmenopausal women consistently Part-time worker 90 9.5 ± 9.1 10.0 90 9.0 ± 11.9 9.8 on HRT, in MHI-5 analyses restricted to Full-time worker 170 8.9 ± 8.4 8.0 170 11.7 ± 11.1 12.2 those assessments that occurred after bone Missing 52 9.6 ± 8.2 9.3 52 12.1 ± 9.8 12.2 lead measurement, there was some sugges- Pack-years of cigarette smoking as of 2004 tion of higher MHI-5 score (less depression) 0 239 9.6 ± 8.8 9.0 238 11.0 ± 10.4 11.7 1–8.9 110 9.2 ± 8.8 9.0 110 11.8 ± 8.8 11.3 with higher patella lead [see Supplemental 9–21.9 122 10.8 ± 10.6 10.7 122 13.0 ± 13.0 10.7 Material, Table 1 (http://dx.doi.org/10.1289/ 22–80 136 12.1 ± 10.0 10.9 136 15.1 ± 12.2 14.0 ehp.1104395)]. There was also a significant Missing 10 11.8 ± 11.1 11.7 10 12.8 ± 13.0 11.3 decrease in anxiety symptoms in the highest Alcohol consumption in 2002 (g/day) tertile of patella bone lead among premeno- < 1.8 218 9.3 ± 8.5 9.6 217 11.5 ± 10.5 12.0 pausal women and postmenopausal women 1.8–8.69 189 10.4 ± 9.3 9.0 189 12.6 ± 11.7 12.2 consistently on HRT (Table 3). However, ≥ 8.7 210 11.3 ± 10.6 10.4 210 13.3 ± 11.5 12.2 this association was seen only in the high- Study subsample Lead and hypertension sample 302 11.7 ± 7.8 10.4 302 15.1 ± 9.5 13.5 est tertile, and precision was poor because of Lead and osteoporosis sample 315 9.1 ± 10.8 8.0 314 9.9 ± 12.2 10.0 small numbers (n = 10 “cases”); the results Postmenopausal hormone use at lead exposure assessment in this tertile likely also drove the significant Premenopausal (never user) 45 9.1 ± 7.6 8.7 45 11.9 ± 10.4 12.2 association with the continuous patella lead Continuous user after menopause 97 9.6 ± 7.8 9.0 97 12.5 ± 9.1 11.3 term (see Supplemental Material, Table 2). Never user or inconsistent user 475 10.6 ± 10.0 10.0 474 12.5 ± 11.7 12.2 All results were essentially unchanged upon aVariables were determined in different years based on date of questionnaire or measure as part of the parent NHS. additional adjustment for hypertension at bone Bone lead levels were standardized to account for differences between measures done before versus after 1999. bn = 616 for patella lead analyses because of missing patella lead data. lead measurement or for whether the nurse’s 820 120 | number 6 | June 2012 • Environmental Health Perspectives ovlume