Testing the consequences of alcohol, cannabis, and nicotine use on hippocampal volume: a quasi-experimental cotwin control analysis of young adult twins

Background Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences. Methods In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI. Results Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use. Conclusions The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.

Prenatal substance exposure and maternal hostility from pregnancy to toddlerhood: Associations with temperament profiles at 16 months of age

We investigated whether infant temperament was predicted by level of and change in maternal hostility, a putative transdiagnostic vulnerability for psychopathology, substance use, and insensitive parenting. A sample of women (N = 247) who were primarily young, low-income, and had varying levels of substance use prenatally (69 nonsmokers, 81 tobacco-only smokers, and 97 tobacco and marijuana smokers) reported their hostility in the third trimester of pregnancy and at 2, 9, and 16 months postpartum, and their toddler's temperament and behavior problems at 16 months. Maternal hostility decreased from late pregnancy to 16 months postpartum. Relative to pregnant women who did not use substances, women who used both marijuana and tobacco prenatally reported higher levels of hostility while pregnant and exhibited less change in hostility over time. Toddlers who were exposed to higher levels of prenatal maternal hostility were more likely to be classified in temperament profiles that resemble either irritability or inhibition, identified via latent profile analysis. These two profiles were each associated with more behavior problems concurrently, though differed in their association with competence. Our results underscore the utility of transdiagnostic vulnerabilities in understanding the intergenerational transmission of psychopathology risk and are discussed in regards to the Research Domain Criteria (RDoC) framework.

476Associations between prenatal perfluoroalkyl substance exposure and cord thyroid hormones using BKMR model

Background Perfluoroalkyl substances (PFASs) are a class of synthetic compounds widely detected in humans. We aimed to examine associations between prenatal PFAS exposure and cord thyroid hormones levels. Methods We studied 300 mother-infant pairs in Shanghai-Minhang Birth Cohort Study. We measured eight PFASs in maternal plasma samples collected at 12-16 gestational weeks, and total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. Bayesian kernel machine regression (BKMR) model was used addressing high correlations between PFAS mixture. Results Maternal PFAS mixture was positively associated with cord T3/FT3 concentrations, such that the 75th percentile of PFAS mixture was associated with 0.074 (95%CI: 0.037, 0.146) nmol/l increase in T3 and 0.095 (95%CI: -0.005, 0.195) pmol/l increase in FT3, compared with the 25th percentile. Regarding single-exposure effect, PFOA at 75th percentile was associated with increased T3 (0.0396 nmol/l, 95%CI: 0.007, 0.072), FT3 (0.159 pmol/l, 95%CI: 0.055, 0.264) and TSH (1.50 uIU/ml, 95%CI: 0.379, 2.621), while PFNA was associated with decreased FT3 (-0.148 pmol/l, 95%CI -0.271, -0.0253) and TSH (-1.621 uIU/ml, 95%CI: -2.959, -0.2835). PFDA was associated with increased FT3 (0.112 pmol/l, 95%CI: -0.0311, 0.2559). Conclusions Prenatal FPAS exposure was positively associated with T3/FT3 with predominant compounds of PFOA, PFNA, and PFDA. Key messages Using BKMR addressing highly correlated PFASs, prenatal exposure to eight PFASs was associated with increased cord T3/FT3 levels with PFOA, PFNA, and PFDA being predominant compounds.

Humidifier disinfectant, sodium dichloroisocyanurate (NaDCC): assessment of respiratory effects to protect workers’ health

In South Korea, it has been found that biocides used to control and eliminate harmful organisms are used as humidifier disinfectants and cause lung disease in users. Hence, efforts have been focused on studying the toxicity of biocides in workers who handle them. The purpose of this study was to evaluate the effects of inhalation exposure to sodium dichloroisocyanurate (NaDCC) to protect the health of workers handling NaDCC. F344 rats were exposed to 0.8-, 4-, and 20-mg/m3 of NaDCC for 6 h per day, 5 days per week for 14 days, and the recovery period after exposure was 14 days. In the 20-mg/m3-exposure group, we observed a decrease in food intake in females, a weight loss in males, and a decrease in partially active thromboplastin time in males and females 2 weeks after exposure. We noted a decrease in white blood cells in males in the 4- and 20-mg/m3-exposed groups. Both males and females in the 20-mg/m3 group and males in the 4-mg/m3 group showed irritation in the larynx related to test substance exposure. However, these findings were not observed in the recovery group. The main target organs affected by repeated 2-week inhalation exposure to NaDCC were the nasal cavity and larynx in the upper respiratory tract. The No Observed Adverse Effect Level (NOAEL) was considered to be 0.8 mg/m3 because effects related to NaDCC exposure were observed even at of 4 mg/m3, and these effects were found to be reversible.