Eva Friedel

Alcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long‐lasting abstinence. In the present study, we analysed resting‐state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified patients with AD ( n = 93) who were followed up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, n = 59), future abstainers (ABS, n = 28) and age‐ and gender‐matched controls (CON, n = 83). Our results suggest increased whole‐brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared with CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared with CON, encompassing regions associated with higher‐order executive functions, sensory and reward processing. Among patients with AD, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow‐up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.

This study investigated the recently reported association between alcohol dependence and accelerated ageing and the potential effects of abstinence and relapse on DNA methylation status using Levine's epigenetic clock to estimate DNA methylation age in two independent cohorts. The first sample comprised 88 (15 female) detoxified patients with alcohol use disorder (AUD) and 32 (5 female) healthy control (CON) subjects (NCT02615977), and the second included 69 (10 female) AUD patients that were followed up for 12 months with respect to relapse ( n = 38, 4 female) and abstinence ( n = 31, 6 female) (NCT01679145). To account for the different aspects of ageing captured by various clocks, we performed additional analyses of the first‐generation Horvath clock and next‐generation Zhang clock. To account for the genetic liability of AUD and its potential influence on DNA methylation, we calculated a polygenic risk score for alcohol dependence. We found that ageing was accelerated by 3.64 years in AUD patients compared with the CON group according to Levine's DNAm PhenoAge. Furthermore, in a second longitudinal sample, we found that abstaining AUD patients displayed a decrease in DNAm PhenoAge by 3.1 years, but we found an over proportional increase by 2.7 years in those who relapsed. Polygenic risk did not affect epigenetic ageing within our sample. These results confirm the age acceleration associated with AUD and provide the first evidence for a recovery of this effect upon abstinence from alcohol.