Kramer, J. R. | Search bioRxiv

bioRxiv2021

Impact of Binge Drinking During College on Resting State Functional Connectivity

AimThe current study aimed to examine the longitudinal effects of standard binge drinking (4+/5+ drinks for females/males in 2 hours) and extreme binge drinking (8+/10+ drinks for females/males in 2 hours) on resting state functional connectivity. Method119 college students with distinct alcohol bingeing patterns (35 non-bingeing controls, 44 standard bingers, and 40 extreme bingers) were recruited to ensure variability in bingeing frequency. Resting state fMRI scans were obtained at time 1 when participants were college freshmen and sophomores and again approximately two years later. On four occasions during the 2-year period between scans, participants reported monthly standard and extreme binge drinking for the past 6 months. Association between bingeing and change in functional connectivity was studied using both network-level and edge-level analysis. Network connectivity was calculated by aggregating multiple edges (a functional connection between any two brain regions) affiliated with the same network. The network-level analysis used mixed-effects models to assess the association between standard/extreme binge drinking and change in network connectivity, focusing on canonical networks often implicated in substance misuse. On the other hand, the edge-level analysis tested the relationship between bingeing and change in whole-brain connectivity edges using connectome-based predictive modeling (CPM). ResultsFor network-level analysis, higher standard bingeing was associated with a decrease in connectivity between Default Mode Network-Ventral Attention Network (DMN-VAN) from time 1 to time 2, controlling for the initial binge groups at time 1, longitudinal network changes, in-scanner motion and other demographic covariates. For edge-level analysis, the CPM failed to identify a generalizable predictive model of cumulative standard/extreme bingeing from change in connectivity edges. ConclusionsOur findings suggest that binge drinking is associated with abnormality in networks implicated in attention allocation and self-focused processes, which, in turn, have been implicated in rumination, craving, and relapse. More extensive alterations in functional connectivity might be observed with heavier or longer binge drinking pattern.

neuroscience↗

bioRxiv2020

Multivariate GWAS elucidates the genetic architecture of alcohol consumption and misuse, corrects biases, and reveals novel associations with disease

Genome-wide association studies (GWASs) of the Alcohol Use Disorder Identification Test (AUDIT), a ten-item screener for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders/medical conditions. To explore these unexpected differences in genetic correlations, we conducted the first item-level and largest GWAS of AUDIT items (N=160,824), and applied a multivariate framework to mitigate previous biases. In doing so, we identified novel patterns of similarity (and dissimilarity) among the AUDIT items, and found evidence of a correlated two-factor structure at the genetic level (Consumption and Problems, rg=.80). Moreover, by applying empirically-derived weights to each of the AUDIT items, we constructed an aggregate measure of alcohol consumption that is strongly associated with alcohol dependence (rg=.67) and several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by performing polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, we identified novel genetic associations between alcohol consumption, alcohol misuse, and human health. Our work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD, and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.

genetics↗