We identified thousands of genes differentially expressed in different cell types and characterized the accompanying differences in chromatin accessibility. We observed an overall increase in both gene expression and chromatin accessibility associated with AUD, which may reflect a heightened state of cellular activity in response to chronic alcohol exposure. Chronic alcohol use has been shown to induce widespread neuroadaptive changes, including alterations in synaptic plasticity in the rodent dorsal striatum51, inflammatory signaling in the human and rat hippocampus and prefrontal cortex24,52, and cellular stress responses, especially along the hypothalamic-pituitary-adrenocortical axis52,53. Here, in our human caudate dataset, we indeed observed differences in enrichment of pathways relating to these processes—such as cytokine/interferon response, innate immune system, and complement cascades—in every cell type that we tested. These observations may therefore represent a composite of responses that emerge as a result of chronic alcohol exposure.
