• Energy Research

AbstractA hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility ofApoelocus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice. Of note, postnatal administration of an APOE receptor agonist (APOE-RA) mitigates motor learning deficits and anxiety in those mice. Several molecular and electrophysiological properties essential for learning, which are altered by PAE, are restored by APOE-RA. Our human genome-wide association study further reveals that the interaction of PAE and a single nucleotide polymorphism in theAPOEenhancer which chromatin is closed by PAE in mice is associated with lower scores in the delayed matching-to-sample task in children. APOE in the plasma is also reduced in PAE children, and the reduced level is associated with their lower cognitive performance. These findings suggest that controlling the APOE level can serve as an effective treatment for neurobehavioral deficits in FASD.

AbstractSome sources report increases in alcohol use have been observed since the start of the COVID-19 pandemic, particularly among women. Cross-sectional studies suggest that specific COVID-19-related stressful experiences (e.g., social disconnection) may be driving such increases in the general population. Few studies have explored these topics among individuals with a history of Alcohol Use Disorders (AUD), an especially vulnerable population. Drawing on recent data collected by the Collaborative Study on the Genetics of Alcoholism (COGA; COVID-19 study N = 1651, 62% women, age range: 30–91) in conjunction with AUD history data collected on the sample since 1990, we investigated associations of COVID-19 related stressors and coping activities with changes in drunkenness frequency since the start of the pandemic. Analyses were conducted for those without a history of AUD (N: 645) and three groups of participants with a history of AUD prior to the start of the pandemic: (1) those experiencing AUD symptoms (N: 606), (2) those in remission who were drinking (N: 231), and (3) those in remission who were abstinent (had not consumed alcohol for 5+ years; N: 169). Gender-stratified models were also examined. Exploratory analyses examined the moderating effects of ‘problematic alcohol use’ polygenic risk scores (PRS) and neural connectivity (i.e., posterior interhemispheric alpha EEG coherence) on associations between COVID-19 stressors and coping activities with changes in the frequency of drunkenness. Increases in drunkenness frequency since the start of the pandemic were higher among those with a lifetime AUD diagnosis experiencing symptoms prior to the start of the pandemic (14% reported increased drunkenness) when compared to those without a history of AUD (5% reported increased drunkenness). Among individuals in remission from AUD prior to the start of the pandemic, rates of increased drunkenness were 10% for those who were drinking pre-pandemic and 4% for those who had previously been abstinent. Across all groups, women reported nominally greater increases in drunkenness frequency when compared with men, although only women experiencing pre-pandemic AUD symptoms reported significantly greater rates of increased drunkenness since the start of the pandemic compared to men in this group (17% of women vs. 5% of men). Among those without a prior history of AUD, associations between COVID-19 risk and protective factors with increases in drunkenness frequency were not observed. Among all groups with a history of AUD (including those with AUD symptoms and those remitted from AUD), perceived stress was associated with increases in drunkenness. Among the remitted-abstinent group, essential worker status was associated with increases in drunkenness. Gender differences in these associations were observed: among women in the remitted-abstinent group, essential worker status, perceived stress, media consumption, and decreased social interactions were associated with increases in drunkenness. Among men in the remitted-drinking group, perceived stress was associated with increases in drunkenness, and increased relationship quality was associated with decreases in drunkenness. Exploratory analyses indicated that associations between family illness or death with increases in drunkenness and increased relationship quality with decreases in drunkenness were more pronounced among the remitted-drinking participants with higher PRS. Associations between family illness or death, media consumption, and economic hardships with increases in drunkenness and healthy coping with decreases in drunkenness were more pronounced among the remitted-abstinent group with lower interhemispheric alpha EEG connectivity. Our results demonstrated that only individuals with pre-pandemic AUD symptoms reported greater increases in drunkenness frequency since the start of the COVID-19 pandemic compared to those without a lifetime history of AUD. This increase was more pronounced among women than men in this group. However, COVID-19-related stressors and coping activities were associated with changes in the frequency of drunkenness among all groups of participants with a prior history of AUD, including those experiencing AUD symptoms, as well as abstinent and non-abstinent participants in remission. Perceived stress, essential worker status, media consumption, social connections (especially for women), and relationship quality (especially for men) are specific areas of focus for designing intervention and prevention strategies aimed at reducing pandemic-related alcohol misuse among this particularly vulnerable group. Interestingly, these associations were not observed for individuals without a prior history of AUD, supporting prior literature that demonstrates that widespread stressors (e.g., pandemics, terrorist attacks) disproportionately impact the mental health and alcohol use of those with a prior history of problems.