COVID-19-related stressors and coping activities were associated with changes in the frequency of drunkenness among participants with symptoms of AUD and in both abstinent and non-abstinent participants in remission prior to the pandemic, but not among individuals without a past history of AUD. Among all groups with a history of AUD , perceived stress was associated with increases in drunkenness. Among the remitted-abstinent group, essential worker status was associated with increases in drunkenness. These findings suggest that these may be specific areas of focus for designing intervention and prevention strategies aimed at reducing pandemic-related alcohol misuse among this particularly vulnerable group. Further, these findings support prior literature that demonstrates that widespread stressors disproportionately impact the alcohol use and mental health of those with a prior history of problems. Significant main effects of COVID-19-related stressors and coping activities on changes in drunkenness were not observed among those without a history of AUD but were among those with a history of AUD,rolling flood tables indicating that they may be more vulnerable to pandemic stress-related alcohol misuse. Specifically, among those with past AUD, perceived stress was associated with increases in drunkenness. Among the remitted-abstinent group, essential worker status was associated with increases in drunkenness.
There are many potential explanations for why individuals with a history of AUD may be at increased risk for alcohol use following the stressful period that has encompassed the COVID-19 pandemic, including facing a variety of stressful experiences related to the pandemic itself , sensitization by prior traumatic or stressful events , genetic, and/or neural vulnerabilities. Previous work in COGA and other studies has also shown that many forms of stress are associated with risks for alcohol misuse and problems, particularly among vulnerable individuals. Some studies examining mechanisms involved in increased stress and recurrence of AUD found an increased likelihood of cravings the evening following a stressful event and an increased likelihood of drinking the day after. Interestingly, these studies found that there is a protective effect for the length of time in recovery. Importantly, previous work has also shown that dimensions of interpersonal and social connections are associated with protection from alcohol misuse and problems. Our findings also demonstrated that, among remitted-abstinent men, relationship quality with family and friends was related to decreases in drunkenness. Further, social disconnection was related to increases in drunkenness among remitted-abstinent women. Other studies have found that while general social support does not appear to be a protective factor against recurrence of AUD, positive familial and close relationship support does help to maintain good long-term AUD outcomes. We note above that increases in the frequency of drunkenness were not observed for those without a history of AUD.
Social events and celebrations have historically provided one setting in which individuals consume alcohol. Given the pandemic’s interruption of these activities, this may provide one possible explanation for why those without a history of AUD did not increase their alcohol consumption during the pandemic, despite reporting stressful COVID-19-related experiences. Gender differences were observed in both the change in frequency of drunkenness during the pandemic and the specific risk and protective factors associated with these increases. In the present study, women with AUD symptoms were more likely to report increases in drunkenness frequency since the start of the pandemic compared to women without a history of AUD. This was not observed for men. Interestingly, previous studies show that while there is an association between stress and increased alcohol consumption in both men and women, the same stressful life events may impact them differently, with relapse to AUD more commonly reported in women than in men. In addition to the increased drunkenness frequency observed among women with current AUD, the present study also found essential worker status, perceived stress, and media consumption were associated with increases in drunkenness among women, whereas perceived stress was associated with increases in drunkenness among men. Further, social disconnection was associated with increases in drunkenness among women, whereas relationship quality was associated with decreases in drunkenness in men. Past research on individuals with a history of AUD outside the context of the pandemic has found that gender differences regarding risk for recurrence of AUD are related to differential exposure to stressors, interpersonal relationships, and social isolation.
While this past research generally suggests that women may be more vulnerable to social/relationship stress related drinking, our findings are less straightforward. Our interpretation of the current study findings is that both men and women in remission from AUD were vulnerable to the social relationship consequences of the pandemic. It seems that they were most vulnerable to different aspects of these social relationship consequences; for men increased relationship quality was associated with decreases in drunkenness, whereas for women, decreased social connections were associated with increases in drunkenness. Several lines of evidence from gene x environment interaction studies have shown that genetic risk factors moderate the associations of traumatic exposures with alcohol use behaviors. The current study supports and extends this research in demonstrating that polygenic risk for problematic alcohol use amplifies the association of COVID-19-related stressors and increases in drunkenness and protective factors with decreases in drunkenness among remitted individuals of European ancestry. These findings may be limited given the current methodological challenges applying genetic findings resulting from discovery samples of largely European ancestry to diverse populations, such as COGA’s lifespan study. While research examining the influence of interactions between neural risk factors and traumatic stress on substance use behaviors is less common, our prior research in COGA has demonstrated that neurophysiological and neurocognitive risk factors also amplify the association of traumatic stress on alcohol use behaviors. The current study extends this work by suggesting that low interhemispheric alpha EEG coherence amplifies the association of COVID-19-related stress with increases in drunkenness, and COVID-19-related protective factors with decreases in drunkenness since the start of the pandemic. However, we note that these exploratory interaction effects need replication in larger samples. Importantly, among COGA participants ages 50–90, assessments of coherence could have occurred as long as 30 years prior to COVID-19 questionnaire data, which is likely to have an impact on these findings. Limitations.
The limitations of this study include a reliance on self-reported changes in drunkenness frequency, which are particularly relevant given the documented relationship between alcohol misuse and memory impairments. Further, there is potential for a lack of generalizability of our study’s findings, particularly with respect to age, given that the mean age of the analytic sample was ~51 years old, and individuals who had remitted from AUD were older than individuals with no past AUD or with current symptoms of AUD . Future work should include more detailed subgroup analyses, including the identification of key stressors and healthy coping activities as a function of age and developmental stage, timing of lock downs, seasonality, pandemic duration, and ethnicity. The CRISIS and ABCD questionnaires were initially selected to assess COVID-19-related stressors, coping and substance use. Among these questionnaire items, there were two items focused on alcohol use . We focused on changes in the frequency of drunkenness to get closer to the more ‘problematic’ use of alcohol. The data included in this manuscript is a ‘baseline’ assessment of a longitudinal study designed to assess more nuanced aspects of alcohol use and misuse,flood and drain tray including more comprehensive measures of drinking and drinking problems with a more precise description of time periods to improve recall , assessed at three time points throughout the course of the pandemic. Thus, more detailed and objective measures of alcohol use and problems will be evaluated in future studies. In our full analytic sample, the reliability of the items included in the COVID-19 questionnaires was good . However, we will continue to monitor psychometric properties and conduct tests by AUD status, gender, age and ethnicity as the sample grows. Finally, in both the overall and gender-stratified analyses, change in drunkenness frequency among remitted-abstinent individuals was particularly affected by COVID risk and protective factors. We note that this group is significantly older and has a more severe alcohol-related history compared to other participants with a past AUD . Both age and AUD severity likely have impacts on the associations of drunkenness with COVID risk and protective factors and should be explored in future studies. In conclusion, this study has demonstrated that COVID-19- related stressors were associated with increased drunkenness frequency among COGA participants with a lifetime history of AUD, suggesting that they may be especially vulnerable to some stressors. Furthermore, this study revealed important gender differences in vulnerability to COVID-19-related stressors among those with a history of AUD. Perceived stress, essential worker status, media consumption, social disconnection, and relationship quality are specific areas of focus for designing intervention and prevention strategies aimed at reducing pandemic-related substance abuse.
Although helminth infection is not typically fatal, it is associated with a multitude of pathological conditions, including malnutrition and growth retardation. A majority of soil-transmitted helminths reside in the gastrointestinal tract, where they can negatively impact the host’s nutritional status by stealing nutrients or preventing nutrient absorption by damaging or causing inflammation of the intestinal tissue . Additionally, recent studies have identified new mechanisms by which helminths impact host feeding and metabolism . Gastrointestinal helminth infection was reported to decrease food intake and was beneficial in mice fed a high-fat diet, in which it improved glucose metabolism and reduced adiposity . This effect was partly mediated through T helper type 2 cytokine-activated M2 macrophages in the adipose tissue, which have a known beneficial effect on metabolic homeostasis . In the intestine, helminth infection induced a Th2 cytokine-dependent expansion of tuft cells, which express taste receptors, and cholecystokinin -positive enteroendocrine cells, which secrete hormones that regulate feeding behavior . Overall, these findings support a multifactorial relationship between helminth and host immune response that affects host feeding behavior and metabolism. Identification of new helminth or host-derived factors that regulate this process, and how they affect host health and helminth killing, could provide a better understanding of the pathological or beneficial effects of helminth infection that could be exploited therapeutically. Among the many host-derived molecules that affect feeding and metabolism, endocannabinoids are an important class of lipid molecules that regulate these physiological processes . Endocannabinoids are the body’s natural cannabis-like molecules that signal through cannabinoid receptors, which are highly expressed on neurons . Unsurprisingly, a highly recognized function of endocannabinoids is promoting neurally mediated behaviors such as food intake and reward . Endocannabinoids, however, are generated throughout the body, and cannabinoid receptors are present on extraneuronal cells, including intestinal epithelial cells and immune cells . Signaling by the endocannabinoids, 2-arachidonoylglycerol and anandamide , through cannabinoid receptors on intestinal cells impacts feeding behavior , while signaling on immune cells can promote anti-inflammatory pathways . Despite functional effects on intestinal physiology and immune responses, no studies reported to date have investigated the role of endocannabinoids in parasite infection. In this study, we investigated the expression and function of endocannabinoids in murine infection with Nippostrongylus brasiliensis, a rodent nematode parasite that has a life cycle similar to that of human hookworms . We show that N. brasiliensis infection significantly induces the biosynthesis of endocannabinoids and endocannabinoid-like molecules in the infected lung and intestine. We also performed functional assays to measure endocannabinoid biosynthetic and degradative enzyme activity in infected jejunal tissue, and we observed significantly increased endocannabinoid synthetic but not degradative enzyme activity. Endocannabinoid levels were negatively correlated with early infection induced weight loss, associated with reduced food intake, and N. brasiliensis egg output, suggesting that endocannabinoids are associated with improved host immunity. To test this hypothesis, we employed validated peripheral pharmacological inhibitors of the cannabinoid subtype 1 receptor and CB2R, AM6545 and AM630, respectively, which act peripherally and do not cross the blood-brain barrier . Pharmacological inhibition of CB1R, but not CB2R, significantly increased N. brasiliensis worm burdens and fecal egg output. Increased parasite burden was associated with reductions in Th2 cytokines but not in the Th1 cytokine gamma interferon , suggesting that N. brasiliensis-induced endocannabinoid signaling through CB1R was important for optimal host Th2 immune responses. Strikingly, bio-informatic analyses of the genomes and transcriptome sequencing data sets from N. brasiliensis and other parasitic nematodes, including the hookworms Ancylostoma ceylanicum and Necator americanus, revealed putative genes encoding endocannabinoid synthetic and degradative enzymes.