Apoptotic executioner caspase-3 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors are increased in the OFC of human subjects with AUD. Postmortem human orbitofrontal cortex (OFC), both paraffin-embedded sections and frozen tissue, were assessed by immunohistochemistry (IHC) and Western blot, respectively. (A) Representative image of activated, cleaved caspase-3 in postmortem human OFC. (B) Quantification of activated, cleaved caspase-3 found a 2-fold increase in cleaved caspase-3 +IR cells consistent with cell death. **** p < 0.0001 vs. control, n = 10 per group, paired t-tests. (C) TRAIL death receptor TRAIL-R1/DR4 was increased by 20% in AUD subjects. (D) TRAIL death receptor TRAIL-R2/DR5 was increased by 21% in AUD subjects. * p < 0.05 vs. control.