MAO-B status in alcohol use disorder: a [11C]SL25.1188 PET imaging study of putative astrogliosis

Chronic alcohol exposure may trigger astrogliosis-a process involving hypertrophy and upregulation of astrocyte-specific markers following neuronal stress or injury-as suggested by trends in preclinical studies. However, in vivo evidence of astrogliosis in alcohol use disorder (AUD) is lacking. Here, we investigated the status of the astrocyte marker MAO-B -an enzyme predominantly expressed in astrocytes and upregulated during astrogliosis - using [¹¹C]SL25.1188 positron emission tomography imaging in healthy controls (n = 28) and people with AUD after 3.5 ± 3.7 (n = 24) and 24 ± 7 days (in a subset: n = 8) of abstinence. Clinical symptoms of AUD were assessed, alongside peripheral markers of astrocyte activation and neuronal injury: glial fibrillary acidic protein (GFAP) and neurofilament light chain (NF-L), respectively. While mean [¹¹C]SL25.1188 binding did not differ significantly between people with and without AUD at either abstinence time-point, binding was notably more variable in AUD and inversely correlated with AUD severity, withdrawal and anxiety (p < 0.05). Plasma GFAP and NF-L were elevated in people with AUD. Daily cigarette use was associated with lower [¹¹C]SL25.1188 binding in people with AUD (-40%) and control participants (-33%). These findings reflect variability in MAO-B binding in AUD and support a potential link between lower MAO-B and greater clinical severity. The observed association between cigarette use and lower MAO-B binding replicates prior reports and extends this observation to AUD. The relationship between higher MAO-B binding and lower AUD severity may reflect compensatory reactive astrogliosis. Understanding whether MAO-B status reflects a beneficial or detrimental astrocytic response in AUD may be important for glial-targeted treatments.