Effects of mixtures of polychlorinated biphenyls (PCBs) and three organochlorine pesticides on cognitive function differ between older Mohawks at Akwesasne and older adults in NHANES.

BACKGROUND: Akwesasne Mohawks has been exposed to high concentrations of polychlorinated biphenyls (PCBs) and background levels of organochlorine pesticides, hexachlorobenzene (HCB), dichlorodiphenyl dichloroethylene (DDE), and mirex. We have previously reported relative contributions to the mixture of low- and high-chlorinated PCBs, HCB, and DDE on cognitive decrements in Mohawks of various ages. OBJECTIVE: This study examines differences in the mixture effects of PCB congener groups, HCB, DDE, and mirex on cognitive function in older Mohawks and less PCB-exposed older adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 cycles. METHODS: We used Bayesian kernel machine regression (BKMR) to evaluate the mixture effects of different PCB congener groups, HCB, DDE, and mirex on cognitive function in both populations. Models were adjusted for age, sex, education levels, and race/ethnicity focusing on individuals 60 years and older. RESULTS: Older Mohawks had 3-fold higher mean total PCB concentrations and 1.8-fold higher mirex, but slightly lower mean DDE and HCB levels than NHANES older adults. Higher mixture concentrations were significantly associated with greater cognitive decline. In older Mohawks, low- and high-chlorinated PCBs, HCB, and DDE contributed to the cognitive score decline. In contrast, score decline in older NHANES adults were primarily from high-chlorinated PCBs and DDE with a threshold dose of approximately 2.08-2.27 ng/g and 2.02-2.40 ng/g, respectively. CONCLUSION: Mixtures of PCBs and organochlorine pesticides increase the risk of cognitive decline in both older Mohawks and NHANES older adults. However, contributions to these mixture effects show significant differences. In older Mohawks, high- and low-chlorinated PCBs, DDE, and HCB are the primary contributors, while high-chlorinated PCBs and DDE are important contributors in NHANES older adults. Due to chronic heavy exposures to PCBs, older Mohawks had a significantly increased risk of cognitive decline compared to general older adults from NHANES.

Mixture Effects of Polychlorinated Biphenyls (PCBs) and Three Organochlorine Pesticides on Cognitive Function in Mohawk Adults at Akwesasne.

The Mohawks at Akwesasne have been highly exposed to polychlorinated biphenyls (PCBs), via releases from three aluminum foundries located near the reserve. They are also exposed to organochlorine pesticides, namely hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex. Previous studies have demonstrated reduced cognition in relation to total PCBs, but the effects of the mixtures of different PCB congener groups, HCB, DDE, and mirex on cognitive function have not been studied. Therefore, cognitive performance for executive function, scored via the digit symbol substitution test (DSST), in Mohawk adults aged 17-79 years (n = 301), was assessed in relation to serum concentrations of low-chlorinated PCBs, high-chlorinated PCBs, total PCBs, HCB, DDE, and mirex. We used mixture models employing the quantile-based g-computation method. The mixture effects of low-chlorinated PCBs, high-chlorinated PCBs, HCB, DDE, and mirex were significantly associated with 4.01 DSST scores decrements in the oldest age group, 47-79 years old. There were important contributions to mixture effects from low-chlorinated PCBs, high-chlorinated PCBs, and total PCBs, with smaller contributions of HCB and DDE. Our findings indicate that exposures to both low- and high-chlorinated PCBs increase the risk of cognitive decline in older adults, while DDE and HCB have less effect.

A Pilot Study to Examine Psychological and Neuropsychological Outcomes and a Novel Detoxification Program for Gulf War Illness.

INTRODUCTION: Exposures to environmental toxins have been associated with severe health problems for approximately one-quarter of the nearly 700,000 U.S. soldiers who served in the Gulf War between the years 1990 and 1991. Gulf War illness still affects about 30% of Gulf War veterans (GWV), causing reduced psychological wellness and neuropsychological function. METHOD AND MATERIALS: This pilot study used a randomized wait-list control design to explore the feasibility and efficacy of a novel detoxification method for GWV exposed to toxicants such as pesticides, nerve gases, and pyridostigmine bromide. Our study included 32 GWV (67% male), with a mean age of 51 (range: 43-70, SD = 6.97), who participated in a 4- to 5-week treatment that was hypothesized to reduce the reported psychological and neuropsychological symptoms. Psychological measures used included tests given for the evaluation of neurocognitive function, including motor function for a dominant hand with the grooved pegboard test; verbal and visual immediate and delayed memory with the Wechsler Memory Scale III abbreviated subtests; executive function domains of attention, speed, and mental flexibility with trail making test parts A and B and Stroop color and word test. Psychological status was measured using the nine subscales of the Symptom Checklist-90-Revised. RESULTS: Primary outcomes included between-group differences in self-reported psychological measures and a neuropsychological battery at 7-day and 3-month assessments. Baseline comparison revealed improvements in 16 of 19 psychological and neuropsychological measures at 7-day assessment and that 13 remained stable at 3-month assessment. CONCLUSIONS: We conclude that the detoxification procedure provided improvement in psychological and cognitive function for GWV and that future study is warranted.

A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial.

Approximately 30% of the 700,000 US veterans of the 1990-1991 Persian Gulf War developed multiple persistent symptoms called Gulf War illness. While the etiology is uncertain, several toxic exposures including pesticides and chemical warfare agents have shown associations. There is no effective medical treatment. An intervention to enhance detoxification developed by Hubbard has improved quality of life and/or reduced body burdens in other cohorts. We evaluated its feasibility and efficacy in ill Gulf War (GW) veterans in a randomized, waitlist-controlled, pilot study at a community-based rehabilitation facility in the United States. Eligible participants (n = 32) were randomly assigned to the intervention (n = 22) or a four-week waitlist control (n = 10). The daily 4-6 week intervention consisted of exercise, sauna-induced sweating, crystalline nicotinic acid and other supplements. Primary outcomes included recruitment, retention and safety; and efficacy was measured via Veteran's Short Form-36 (SF-36) quality of life, McGill pain, multidimensional fatigue inventory questionnaires and neuropsychological batteries. Scoring of outcomes was blinded. All 32 completed the trial and 21 completed 3-month follow-up. Mean SF-36 physical component summary score after the intervention was 6.9 (95% CI; -0.3, 14.2) points higher compared to waitlist control and 11 of 16 quality of life, pain and fatigue measures improved, with no serious adverse events. Most improvements were retained after 3 months. The Hubbard regimen was feasible, safe and might offer relief for symptoms of GW illness.

"We Need to Make Action NOW, to Help Keep the Language Alive": Navigating Tensions of Engaging Indigenous Educational Values in University Education.

Despite centuries of contact and conquest, Indigenous communities persist in maintaining their cultures and psychologies. Key to this success in cultural survival is the maintenance of Indigenous languages, which contain distinct worldviews. However, Indigenous languages are at risk, with fewer and fewer fluent Elder speakers. Fortunately, there remain committed groups of community educators who carry out Indigenous language education. Current mainstream teacher education programs do not typically introduce the importance of Indigenous language education to teacher candidates, who are the next generation of K-12 teachers. We view this as highly problematic, and thus carried out a proof-of-concept project in which one U.S. university's American Indian/Alaska Native teacher candidates collaborated with, and learned from, Indigenous language educators during a two-week-long summer institute at the university. In our article, we share three main findings, based on qualitative analyses of daily-written student journals collected during the two-week pilot project: (a) Indigenous language education supports the social justice vision in the American Psychological Association's Multicultural Guidelines; (b) intergenerational educational opportunities are invaluable for affirming Indigenous psychologies; and (c) Indigenous community language educators do important survivance work. Our findings provide insight into how Indigenous language education is crucial for advancing education that honors Indigenous community psychological well-being.

Diabetes Prevalence in Relation to Serum Concentrations of Polychlorinated Biphenyl (PCB) Congener Groups and Three Chlorinated Pesticides in a Native American Population.

BACKGROUND: Exposure to persistent organic pollutants (POPs) is known to increase risk of diabetes. OBJECTIVE: To determine which POPs are most associated with prevalence of diabetes in 601 Akwesasne Native Americans. METHODS: Multiple logistic regression analysis was used to assess associations between quartiles of concentrations of 101 polychlorinated biphenyl (PCBs) congeners, congener groups and three chlorinated pesticides [dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and mirex] with diabetes. In Model 1, the relationship between quartiles of exposure and diabetes were adjusted only for sex, age, body mass index (BMI), and total serum lipids. Model 2 included additional adjustment for either total PCBs or total pesticides. RESULTS: Total serum PCB and pesticide concentrations were each significantly associated with prevalence of diabetes when adjusted only for covariates (Model 1), but neither showed a significant OR for highest to lowest quartiles after additional adjustment for the other (Model 2). When applying Model 2 to PCB congener groups and individual pesticides, there were significant omnibus differences between the four quartiles (all ps < 0.042) for most groups, with the exception of penta- and hexachlorobiphenyls, DDE and mirex. However, when comparing highest to lowest quartiles only non- and mono-ortho PCBs [OR = 4.55 (95% CI: 1.48, 13.95)], tri- and tetrachloro PCBs [OR = 3.66 (95% CI: 1.37, -9.78)] and HCB [OR = 2.64 (95% CI: 1.05, 6.61)] showed significant associations with diabetes. Among the non- and mono-ortho congeners, highest to lowest quartile of dioxin TEQs was not significant [OR = 1.82 (95% CI: 0.61, 5.40)] but the OR for the non-dioxin-like congeners was [OR = 5.01 (95% CI: 1.76, 14.24)]. CONCLUSION: The associations with diabetes after adjustment for other POPs were strongest with the more volatile, non-dioxin-like, low-chlorinated PCB congeners and HCB. Because low-chlorinated congeners are more volatile, these observations suggest that inhalation of vapor-phase PCBs is an important route of exposure. CITATION: Aminov Z, Haase R, Rej R, Schymura MJ, Santiago-Rivera A, Morse G, DeCaprio A, Carpenter DO, and the Akwesasne Task Force on the Environment. 2016. Diabetes prevalence in relation to serum concentrations of polychlorinated biphenyl (PCB) congener groups and three chlorinated pesticides in a Native American population. Environ Health Perspect 124:1376-1383; http://dx.doi.org/10.1289/ehp.1509902.

Lower serum testosterone associated with elevated polychlorinated biphenyl concentrations in Native American men.

BACKGROUND: Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. OBJECTIVE: We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. METHODS: We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. RESULTS: Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05-0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06-0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. CONCLUSIONS: Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men.

Evidence of an age-related threshold effect of polychlorinated biphenyls (PCBs) on neuropsychological functioning in a Native American population.

Polychlorinated biphenyls (PCBs) have been suspected for some time of having adverse effects on neuropsychological functioning in humans. While there is evidence of slowing of cognitive function in children associated with exposure to PCBs, the evidence of comparable effects on adults is far less well understood. We report here on the neuropsychological evaluation of 277 Native American adults, ranging in age from 18 to 79, who were exposed to PCBs by way of environmental contamination in the St. Lawrence region of upstate New York. PCB body burden was estimated by 101 PCB congeners and neuropsychological functioning was assessed by a battery of 18 tests. Spline regression models were fitted to the latent variables of memory, motor function, and higher-order executive functioning. After adjusting for age, gender, and education the analyses revealed a threshold effect of PCBs at approximately 2 ppb. An age-by-PCB interaction effect was also observed for several variables which suggests that the threshold effect was largely confined to the age range of 40-79 and was not observable in the 18-40-year-old group. Implications of these results are discussed in comparison to previously published similar work with adults and in terms of its potential clinical meaningfulness.

High serum PCBs are associated with elevation of serum lipids and cardiovascular disease in a Native American population.

We have investigated the relationships among the concentration of total serum polychlorinated biphenyls (PCBs), various PCB congener groupings, and three pesticides to total serum lipids in humans with and without self-reported cardiovascular disease. Blood samples were obtained from 335 adult Akwesasne Mohawks, and were analyzed for 101 PCB congeners, mirex, dichloro-diphenyl-dichloro-ethylene (DDE), and hexachlorobenzene (HCB), as well as serum triglycerides and cholesterol. Structural equation modeling, following the definition of latent variables by means of confirmatory factor analysis, was used to analyze the relationships between serum lipids with PCBs and heart disease. There were significant associations among PCBs, lipids, age, and body mass index (BMI), a fact which justified the application of the structural equation model. Gender of the participant was unrelated to any of the remaining study variables. The results of this study are consistent with a model in which age is considered as both an exogenous explanatory variable and a biological driving mechanism for the acquisition of PCBs. Moreover, the results of this study are consistent with the conclusion that PCBs, acting through P450 enzymes, are directly responsible for increased synthesis of cholesterol and triglycerides, substances known to be major risk factors for cardiovascular disease.

Polychlorinated biphenyl (PCB) exposure assessment by multivariate statistical analysis of serum congener profiles in an adult Native American population.

The major determinants of human polychlorinated biphenyl (PCB) body burden include the source and route of exposure and the toxicokinetic processes occurring after uptake. However, the relative importance of each factor for individual subjects cannot currently be determined. The present study characterizes levels and patterns of PCB congeners in a large cohort of adult Akwesasne Mohawks with historical PCB exposure. Total serum PCB ranged from 0.29 to 48.32 ng/g and was higher in adult men than in women (median of 3.81 vs. 2.94 ng/g). The mean serum congener profile for the full cohort was dominated by persistent penta- to hepta-chlorinated biphenyls; several labile congeners were also prominent. In order to provide additional information on individual body burden determinants, multivariate exploratory data analysis techniques were applied to the congener-specific serum PCB data. A self-training receptor model, polytopic vector analysis (PVA), was employed to determine the number, composition, and relative proportions of independent congener patterns that contributed to the overall serum PCB profile for each Mohawk subject. PVA identified five such patterns, each of which was characterized by a unique mix of congeners. One pattern observed in a limited number of Mohawks was similar to those reported for air sampled near contaminated sediment deposits at Akwesasne and for volatilized Aroclor 1248 and is hypothesized to reflect recent inhalation exposure in these subjects. A second pattern was consistent with unaltered Aroclor 1254. A third pattern, resembling Aroclor 1262 but without labile congeners, was correlated with age and is interpreted as representing a lifetime PCB accumulation profile. The final two patterns were dominated by subsets of major persistent congeners and are hypothesized to reflect intermediate bioaccumulation profiles and/or differences in individual toxicokinetics. The results confirm the utility of a multivariate exploratory analysis approach to congener-specific PCB data and provide additional insight into the exposure and individual factors that determine PCB body burden in this population.