Drug use disorder following early life exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

BACKGROUND: Many studies of adults with occupational exposure to solvents such as tetrachloroethylene (PCE) have shown adverse effects on cognition, mood and behavioral problems. Much less is known about neurotoxic effects in early life at lower exposure levels seen in community settings. We recently reported that illicit drug use was more frequent among adults from Cape Cod, Massachusetts who were exposed to PCE-contaminated drinking water during gestation and early childhood than their unexposed counterparts. Using newly collected data from this population-based retrospective cohort study, the current analysis examines whether early life PCE exposure is also associated with drug use disorder over the life course. METHODS: Three-hundred and sixty-three subjects with prenatal and early childhood PCE exposure and 255 unexposed subjects were studied. These individuals (median age: 40-41 years) completed self-administered questionnaires on the eleven established diagnostic criteria for drug use disorder and confounding variables. A validated leaching and transport model was used to estimate exposure to PCE-contaminated water. RESULTS: Overall, 23.3% of subjects reported having at least one criterion for drug use disorder over their lifetime. Early life PCE exposure was associated with a modest increase in the lifetime presence of one or more diagnostic criteria for drug use disorder (adjusted RR: 1.4, 95% CI: 1.0-1.8). Compared to unexposed subjects, PCE-exposed subjects were more likely to report having most diagnostic criteria of drug use disorder, including neglecting major roles due to drug use, physical and psychological problems related to drug use, and giving up activities due to drug use. No dose-response relationships were observed with increasing levels of PCE exposure. CONCLUSIONS: These results suggest that exposure to PCE-contaminated drinking water during early life modestly increases the risk of developing diagnostic criteria for drug use disorder later in life. Because this study has several limitations, these findings should be confirmed in follow-up investigations of other exposed populations with more diverse racial and socioeconomic characteristics.

Association between resilience promotion factors during childhood and risk of drug use disorder during adulthood.

Few studies have been conducted on the relationship between "outside-residing" resilience characteristics and the risk of developing drug use disorder later in life. These characteristics include responsive and caring parenting, household routines involving regular family meals and bedtime routines, social support from peers, participation in organized activities, and religious service attendance. We quantified the association between these resilience promotion factors during childhood and the risk of developing criteria for drug use disorder during adulthood using data from a retrospective cohort study of 618 adults born in Massachusetts during 1969-1983, including those with adverse childhood experiences (ACEs). Self-administered questionnaires gathered information on criteria for drug use disorder, ACEs, and family and community resilience promotion factors. Compared to individuals with "low" numbers of resilience promotion factors, 30% (95% CI: 0.5-0.9) and 50% reductions (95% CI: 0.4-0.8) in the risk of developing one or more criteria for drug use disorder were observed among those with "moderate" and "high" numbers of resilience factors, respectively (p value for trend=0.003). Overall, family factors were associated with greater risk reductions than comparable numbers of community factors. Among individuals with ACEs, a "high" number of family factors but not community factors were associated with a reduction in risk (RR:0.6, 95% CI:0.4-1.0 for family factors, RR:1.0, 95% CI:0.5-1.8 for community factors). These results suggest that the risk of developing criteria for drug use disorder decreases in a dose-response fashion according to the number of "outside-residing" resilience promotion factors during childhood, and that family factors are associated with greater risk reductions than community factors, particularly among individuals with ACEs. Coordinated prevention efforts at the family and community level are recommended to reduce the risk of this important societal problem.

Association of Common and Rare Variants with Alzheimer's Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer's Disease Sequencing Project.

Alzheimer's Disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. Here, we investigated the association between AD and both common variants and aggregates of rare coding and noncoding variants in 13,371 individuals of diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic variants in or near APOE, BIN1, and LINC00320 significantly associated with AD (p < 5×10-8). Population-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and noncoding variants in this region. Finally, we observed suggestive associations (p < 5×10-5) of aggregates of rare coding rare variants in ABCA7 among non-Hispanic Whites (p=5.4×10-6), and rare noncoding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p=7.2×10-8). Complementary pooled-population and population-specific analyses offered unique insights into the genetic architecture of AD.