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Objective: Alcohol consumption patterns during the COVID-19 pandemic have varied notably. Participants: We examined the acute impact of the pandemic on alcohol use disorder (AUD) in a generalizable sample of college students who were surveyed pre-pandemic and re-surveyed in May 2020. Method: Items assessed pre-pandemic included DSM-5 AUD and mental health symptoms. A COVID-19 impacts questionnaire was administered, and alcohol and mental health items re-assessed. Results: AUD symptoms decreased from pre-pandemic to during the pandemic, demonstrating a change in trajectory compared to prior cohorts. Students with persistent AUD reported greater concurrent symptoms of PTSD, depression, and alcohol consumption than those with remitted AUD (ps ≤.02), but not increased COVID-19 impact. Persistent AUD status was predicted by higher sensation seeking and alcohol consumption. Conclusions: Students with concurrent mental health problems are at continued risk for persistent AUD. Findings highlight the impact of the college environment and social context for drinking on AUD. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a common, clinically and economically impactful psychiatric disorder. Genetic discovery for PTSD has accelerated at a rapid pace with nearly 100 common variants identified from genome-wide association studies (GWAS). However, large-scale studies of rare variants associated with PTSD using next-generation sequencing data have not yet been conducted. Here, we analyzed the latest whole-exome-sequencing (WES) dataset from the UK Biobank (UKB) to detect genes and gene-sets containing rare variation associated with PTSD. We conducted rare variant analyses using WES based genotypes and in 133,738 samples of European ancestry with mental health questionnaire data. PTSD phenotypes were defined from these questionnaire data. First, we used established quality-control steps for WES data. Next, synonymous, missense and loss-of-function variants were identified for analyses. We then ran SAIGE-GENE+ to generate variant and gene-level p-values for variants with a minor allele frequency (MAF) < 0.01. The GAUSS package was then used to conduct gene-set enrichment analysis for gene-level p-values. Gene-sets were selected from a wide variety of sources including the Psychiatric Genomics Consortium GWAS meta-analysis of PTSD in 2024 and curated gene-sets from studies of neuropsychiatric disorders. For variant-level analysis, there were no genome-wide significant variants detected with the most significant variant being chr1:152356894:A:G in the FLG2 gene (p = 4.98 × 10-7, MAF < 0.01). For gene-level analysis of 18,190 genes, only MAST4 was nominally significant (p = 8.2 × 10 6) for loss-of-function and missense variants. For gene-set enrichment analysis, 10 out of 189 tested gene-sets were nominally significant but not significant after multiple testing correction. Eight of these 10 gene-sets were from mouse mutants with central nervous system phenotypes with the most significant (p=0.003) being related to abnormal innervation. The remaining two gene-sets were from studies of other neuropsychiatric disorders. Finally, the gene-set from the latest PGC PTSD GWAS meta-analysis had a modest p-value of 0.089. For rare variant analysis, robustly statistically significant associations with a proxy phenotype of PTSD were not observed, even with a large sample (133k). However, nominally significant gene MAST4 has been previously associated with neurodevelopmental disorders. Similarly, some nominally enriched gene-sets were from studies of previous neuropsychiatric disorders. Notably, the gene-set from the latest common variant GWAS study had a modest p-value in this analysis. Future studies which focus on understanding the overlapping information of these types of variants can shed additional light on the genetic architecture of PTSD. Our future extensions of these analyses will include integrative analytic approaches and importantly expand to multiple ancestry samples across several biobanks in order to advance the understanding of PTSD. This study was conducted using the UK Biobank Resource application number 30782. [ABSTRACT FROM AUTHOR]