Postmortem human brain samples were obtained, following consent from the next of kin, during autopsies conducted by the Allegheny County Office of the Medical Examiner (Pittsburgh, PA). Consent was obtained from next-of-kin and procedures were approved by the University of Pittsburgh’s committee for Oversight of Research and Clinical Training Involving Decedents and Institutional Review Board for Biomedical Research. An independent committee of clinicians made consensus, lifetime DSM-IV diagnoses for each individual using the results of an expanded psychological autopsy, including structured interviews with family members and review of medical records, as well as toxicological and neuropathological reports123. The same approach was used to confirm the absence of lifetime psychiatric and neurologic disorders in the unaffected comparison individuals. All procedures were approved by the University of Pittsburgh Committee for Oversight of Research and Clinical Training Involving Decedents and Institutional Review Board for Biomedical Research. Each individual meeting diagnostic criteria for OUD at the time of death (n = 6) was matched with an unaffected comparison individual (n = 6) for sex and as closely as possible for age and PMI (see Supplementary Data 1–S5). The duration of illness for each individual with OUD was at least four years prior to death.
