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FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study.

ABSTRACT: Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in N = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17-46.56, p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02-0.75, p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726, p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.

SUBMITTER: Bach P

PROVIDER: S-EPMC8236024 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrecision medicine aims to identify those patients who will benefit the most from specific treatments. Recent work found large effects of naltrexone among "reward drinkers," defined as individuals who drink primarily for the rewarding effects of alcohol. This study sought to replicate and extend these recent findings by examining whether the desire to drink mediated the effect of naltrexone among reward drinkers.MethodsWe conducted a secondary analysis of a 12-week randomized clinical trial of daily or targeted naltrexone among problem drinkers (n = 163), with a focus on 86 individuals (n = 45 naltrexone and n = 41 placebo) who received daily medication. Interactive voice response technology was used to collect daily reports of drinking and desire to drink. Factor mixture models were used to derive reward and relief phenotypes. Moderation analyses were used to evaluate naltrexone effects, with phenotype as a moderator variable. Multilevel mediation tested average desire to drink as a mediator.ResultsResults indicated 4 phenotypes: low reward/low relief; low reward/high relief; high reward/low relief; and high reward/high relief. There was an interaction between the high reward/low relief subgroup (n = 10) and daily naltrexone versus placebo on drinks per drinking day (DPDD; p = 0.03), percent heavy drinking days (p = 0.004), and daily drinking (p = 0.02). As compared to placebo, individuals in the high reward/low relief phenotype who received daily naltrexone had significantly fewer DPDD (Cohen's d = 2.05) and had a lower proportion of heavy drinking days (Cohen's d = 1.75). As hypothesized, reductions in average desire to drink mediated the effect of naltrexone on average daily drinking among the high reward/low relief drinkers (moderated mediation effect: p = 0.029).ConclusionsThis theory-driven study replicates the empirical finding that naltrexone is particularly efficacious among high reward/low relief drinkers. Our study brings the field a step closer to the potential of using a precision medicine approach to treating alcohol use disorder.

Project description:Background and aimsThe DSM-IV personality disorders (PDs) are comorbid with alcohol use disorder (AUD) and with each other. It remains unclear which PD criteria are most likely to drive onset and recurrence of AUD and which are merely confounded with those criteria. We determine which individual PD criteria predict AUD and the degree of underlying genetic and/or environmental aetiology.DesignA prospective observational twin study.SettingNorway 1999-2011.ParticipantsA total of 2528 and 2275 Norwegian adult twins in waves 1 and 2 variable-selection analyses, and 2785 in biometric analyses.MeasurementsDSM-IV PDs and their 80 criteria were assessed using a structured personal interview, and AUD using the World Health Organization's Composite International Diagnostic Interview.FindingsIn a variable-selection analysis, two PD criteria were associated with AUD even after taking all the other criteria into account: criterion 8 of antisocial PD (childhood conduct disorder) and criterion 4 of borderline PD (self-damaging impulsive behaviours). Adjusting for each other, their respective odds ratios were 3.4 [confidence interval (CI) = 2.1-5.4] and 5.0 (CI = 3.3-7.7). Endorsement strength of the criteria was associated with AUD in a dose-response manner and they explained 5.5% of variation in AUD risk-more than the full diagnoses of antisocial and borderline PDs together (0.5%). The association between borderline criterion 4 and AUD 10 years later derived mainly from their overlapping genetic factors, whereas the association between antisocial criterion 8 and AUD 10 years later was due to both genetic and non-genetic factors.ConclusionsConduct disorder and self-harming impulsivity are the foremost risk traits for alcohol use disorder among the 80 personality disorder criteria of DSM-IV, predicting alcohol use disorder more effectively than personality disorder diagnoses. The twin-study analysis suggested that conduct disorder represents a joint genetic and developmental risk for alcohol use disorder and that impulsivity is a genetic risk.

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FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study.

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