Hippocampal volume alterations in opioid use disorder: Evidence for posterior vulnerability and heterogeneity

Evidence is emerging that chronic exposure to opioids can impact brain structure, with preclinical studies demonstrating alterations in subcortical regions, including the hippocampus; however, corresponding evidence in humans remains limited. The present study investigates whether individuals with opioid use disorder (OUD) exhibit smaller hippocampal volumes relative to controls and explores heterogeneity within the OUD group as well as associations between hippocampal volume and cognitive performance. Participants with OUD (n = 94) and controls (n = 40) completed a structural magnetic resonance imaging scan, and a subset of 18 OUD and 10 controls who completed a standardized neurocognitive battery. Hippocampal volumes were extracted using the Automatic Segmentation of Hippocampal Subfields (ASHS). Primary analyses examined group differences in bilateral whole, anterior, and posterior hippocampus. Exploratory analysis assessed heterogeneity within OUD (e.g., methadone-treated vs buprenorphine-treated vs no treatment) and associations between hippocampal volumes and cognitive performance. Individuals with OUD exhibited significantly smaller left and right hippocampal volumes relative to controls. When examining anterior vs posterior subregions, significant effects were strongest in the posterior right hippocampus. Exploratory analyses further suggested significant heterogeneity within the OUD group, with methadone-treated individuals exhibiting smaller posterior volumes relative to controls and buprenorphine-treated participants. In the neurocognitive subset, hippocampal volume was associated with episodic memory performance. These findings suggest that OUD is associated with smaller hippocampal volumes and that clinically meaningful heterogeneity exists within OUD populations, warranting further investigation into the mechanisms underlying these differences.