Addiction Biology最新文献

{"title":"GABAergic Network Dysregulation in Alcohol Use Disorder: Receptor-Transporter Interactions Driving the Transition From Goal-Directed to Compulsive Behaviour.","authors":"Hannah Aranda, Nathan Jones, Humza Haroon, Doo-Sup Choi","doi":"10.1111/adb.70195","DOIUrl":"10.1111/adb.70195","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) is characterized by a shift from controlled, goal-directed drinking to compulsive, habitual alcohol (a.k.a. ethanol) seeking, even in the face of negative outcomes. This transition is closely associated with alterations in cortico-striatal circuitry and dysregulated GABAergic signalling, both of which drive the progression from flexible control to compulsive behaviour. Acute alcohol exposure enhances GABAergic inhibition, primarily by increasing presynaptic GABA release. Chronic exposure leads to compensatory neuroadaptations, such as subunit reorganization, receptor internalization and diminished GABA receptor sensitivity. While these neuroadaptations alter receptor-mediated GABAergic signalling during dependence and withdrawal, they also alter dopaminergic regulation and further reinforce alcohol-seeking behaviour. Beyond receptor-level adaptations, impaired GABA clearance, especially through the astrocytic transporter GAT3, plays a crucial role in regulating extracellular GABA concentrations and tonic inhibition. This effect is particularly evident within the dorsal striatum, where elevated tonic GABA shifts control from flexible, goal-directed action towards rigid, habitual responding by altering the balance between the dorsomedial and dorsolateral subregions. Consistent with these mechanistic insights, animal and human studies demonstrate that reduced GAT3 expression is associated with compulsive alcohol use and impaired reward-related behaviour, reinforcing impaired GABA clearance as a central mechanism in this behavioural shift. Taken together, these lines of evidence validate a central therapeutic model, namely, that targeting altered tonic inhibition and impaired GABA clearance in AUD could address the inhibitory dysfunction that sustains the disorder. Overall, this work supports a unifying model in which receptor adaptations and disrupted GABA removal maintain altered inhibitory tone, driving maladaptive circuit function and contributing to the persistence of AUD.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 11","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149289498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative Affective States Are Not Detected in Rats Following an Intravenous Self-Administration Regimen Leading to Incubation of Oxycodone Craving.","authors":"Amanda M Wunsch, Kimberley A Mount, Asia Guzman, Alex B Kawa, Jonathan G Westlake, Hayley M Kuhn, Madelyn M Beutler, Marina E Wolf","doi":"10.1111/adb.70196","DOIUrl":"https://doi.org/10.1111/adb.70196","url":null,"abstract":"<p><p>In rats, cue-induced opioid craving intensifies (incubates) during abstinence from opioid self-administration and then remains high for a prolonged period. The prolonged plateau models persistent vulnerability to cue-induced craving and relapse in humans recovering from opioid use disorder. However, a very significant contributor to relapse vulnerability in these individuals is the presence of negative affective states that can persist for months to years, far beyond physical dependence. The goal of this study was to determine, for oxycodone, if the incubation of craving model recapitulates this aspect of relapse vulnerability. We began by comparing rats trained to self-administer oxycodone using a regimen leading to persistent elevation of cue-induced craving (6 h/day × 10 days) and rats trained to self-administer saline. We assessed somatic withdrawal signs in early abstinence and conducted behavioural tests modelling negative affect (open field, social preference, sucrose preference and elevated plus maze) in late abstinence. Some oxycodone rats exhibited somatic withdrawal signs on abstinence day (AD)1. However, on AD41-46, no group differences were found in behavioural tests modelling negative affect. To compare early and late abstinence periods, a second cohort of rats self-administered saline or oxycodone and then received a sequence of tests (cue-induced seeking test followed by negative affect tests) in early abstinence (AD1-7) and again in late abstinence (AD40-46). While some time-dependent changes in affect were observed within each group, they did not indicate emergence of negative affect in oxycodone rats during incubation of craving. In conclusion, our results suggest that rats exhibiting incubation are not seeking the drug to relieve an aversive state that persists into protracted abstinence. An alternative explanation is that incubated seeking reflects increased incentive salience of the drug-paired cue. Our finding of modest somatic withdrawal signs in early abstinence and no detectable negative affective states in late abstinence probably reflects lower drug intake during the intravenous regimen compared to non-contingent escalating dose regimens typically used to study withdrawal signs. Thus, while the incubation model has utility for studying cue-induced oxycodone craving, our standard incubation regimen is not suited to studying oxycodone seeking driven by the desire to relieve an aversive state.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 11","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149326587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological Arousal During Alcohol Cue Exposure in Adult Drinkers: Sex Differences in Neural and Clinical Correlates: Alcohol Cue Exposure and Arousal.","authors":"Yu Chen, Hak Kei Wong, Shefali Chaudhary, Herta H Chao, Sheng Zhang, Chiang-Shan R Li","doi":"10.1111/adb.70197","DOIUrl":"https://doi.org/10.1111/adb.70197","url":null,"abstract":"<p><p>Cue exposure contributes to craving and reinforces alcohol misuse, potentially by altering interoceptive processing and physiological arousal. However, few studies have reported changes in physiological arousal or their neural underpinnings in response to alcohol cues. Here, we addressed these questions in 94 adult drinkers (39 females; age mean ± SD: 59.1 ± 19.1 years and range: 19-85 years) who underwent functional magnetic resonance imaging and skin conductance recording during alcohol and neutral cue exposures and completed clinical assessments including the Alcohol Use Disorder Identification Test (AUDIT; mean ± SD: 4.4 ± 5.5). Imaging data were processed with published routines and evaluated at a corrected threshold. The results showed significantly higher skin conductance response in 'alcohol>neutral' blocks (SCR_Al-Ne) in females than in males. However, SCR_Al-Ne was positively correlated with participants' AUDIT scores in males but not in females. SCR_Al-Ne was also positively correlated with global positive alcohol expectancy and novelty seeking scores in males but not in females. A voxel-wise two sample test of the contrast 'alcohol>neutral' did not show any clusters with significant sex differences in cue reactivity. Whole-brain regression of the same contrast on AUDIT scores identified a large cluster in the perigenual anterior cingulate cortex (pgACC), with the beta estimates showing a significant positive correlation with the SCR_Al-Ne, again in males only. These sex differences were all confirmed by slope tests. Thus, males with more drinking problems showed higher arousal as well as the pgACC response to alcohol cues in association with alcohol expectancy and novelty seeking. In chain mediation modelling, the pgACC response and alcohol expectancy interlinked SCR_Al-Ne and AUDIT scores in males. In contrast, we failed to observe any significant neural or psychological correlates of physiological arousal, despite higher SCR_Al-Ne, in females. With the caveat of a smaller sample size for females, these findings highlight sex and individual differences in physiological responses to alcohol cues and the neural and psychological underpinnings in male adult drinkers. Whether or how physiological arousal may play a role in the pathophysiology of alcohol misuse remains to be investigated for females.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 11","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149326599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rTMS Suppresses Tobacco Craving via Enhanced Prefronto-Striato-Thalamic Connectivity.","authors":"Xin Luo, Xuefeng Ma, Shuang Li, Hong'an Chen, Bo Yang, Yanbin Zheng, Guang-Heng Dong","doi":"10.1111/adb.70167","DOIUrl":"10.1111/adb.70167","url":null,"abstract":"<p><p>Studies have used repetitive transcranial magnetic stimulation (rTMS) to stimulate the left dorsolateral prefrontal cortex (DLPFC) in patients with tobacco use disorder (TUD); consequently, decreased craving for smoking was observed. However, the neural mechanism underlying this process remains unclear. Functional MRI data were collected from 59 valid TUD participants (31 rTMS and 28 shams) when they performed a Go/No-go task before and after a continuous 5-day treatment (rTMS on the left DLPFC). Three approaches of data analyses were performed: event-related data analyses to identify the brain regions that are associated with rTMS treatment; functional connectivity (FC) analyses among the left DLPFC (the stimulate region) and other survived brain regions after group comparison; FC between the left DLPFC and all brain regions to find couplings among the brain regions. rTMS decreased the craving for smoking in patients with TUD. Comparing with the sham group, the rTMS group showed enhanced brain responses in the bilateral ACC, bilateral caudate and left thalamus to the No-go smoking cues. Further, FC analyses among the survived brain regions showed that rTMS enhanced the FC in DLPFC-caudate and caudate-left thalamus pathways. Notably, enhanced FC between the DLPFC and bilateral basal ganglia thalamus was observed. The current study demonstrated the effectiveness of rTMS in the treatment of TUD, which is associated with enhanced brain responses that are responsible for executive control and reward processing; it enhanced top-down control by reshaping the prefrontal-striatal pathways.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70167"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147934710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Acting Naltrexone Restores Network Connectivity in Subjects With Comorbid Cannabis and Opioid Use Disorder.","authors":"Lindsey M Brier, Daniel D Langleben, Corinde E Wiers, Zhenhao Shi","doi":"10.1111/adb.70159","DOIUrl":"10.1111/adb.70159","url":null,"abstract":"<p><p>Comorbid substance use disorders (SUDs) are common but difficult to study due to the complex, interacting and overlapping mechanisms through which they affect brain networks. Many datasets collected to investigate a specific SUD include participants with comorbid SUDs. Although most studies treat comorbid SUDs as covariates of no interest, these covariates also contain untapped information. This is particularly relevant as cannabis use disorder (CanUD) has become increasingly prevalent and comorbid with other SUDs that have been more thoroughly studied. While pharmacotherapies have been established for multiple SUDs, none have been approved for CanUD, although naltrexone (NTX) has been associated with reduced use. Here, we conducted a retrospective secondary analysis of functional magnetic resonance imaging (fMRI) data from individuals with primary opioid use disorder (OUD-only, N = 25 pre-NTX, N = 20 on-NTX) with comorbid CanUD (N = 10), alcohol use disorder (AUD, N = 6) or cocaine use disorder (CocUD, N = 7). All participants underwent imaging prior to receiving a therapeutic dose of long-acting intramuscular NTX (Vivitrol), an approved treatment for OUD and AUD but not for CocUD, and again 2 weeks postadministration. At baseline, OUD individuals with comorbid CanUD, AUD or CocUD exhibited distinct functional connectivity (FC) alterations compared to those with OUD-only. These differences were greater in younger participants and primarily involved the default mode network. Following NTX administration, FC differences between the comorbid CanUD and OUD-only groups globally diminished. A similar FC response to NTX was observed in the comorbid AUD group, whereas little change in FC was observed in comorbid CocUD. These findings, combined with prior evidence that NTX reduces cannabis use by dampening reward, suggest NTX may hold promise as a treatment for CanUD.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70159"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147965203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical and Subcortical Signatures of Incentive Salience Attribution in Tobacco Use Disorder.","authors":"Nicola Sambuco, Francesco Versace, Brian A Taylor","doi":"10.1111/adb.70151","DOIUrl":"10.1111/adb.70151","url":null,"abstract":"<p><p>Relapse is a defining feature of substance use disorders, yet relapse risk varies widely across individuals. This variability has been linked to individual differences in incentive salience attribution to drug-related cues. We used fMRI to identify cortical and subcortical circuits underlying individual differences in incentive salience attribution among people with tobacco use disorder. Fifty daily cigarette users viewed pleasant, unpleasant, cigarette-related and neutral images during task-based fMRI and completed a resting-state scan. We extracted per-condition BOLD activity from a functionally defined extended visual region (Emotional > Neutral) and applied k-means clustering (k = 2) to derive neuroaffective profiles. Whole-brain voxelwise tests assessed Group × Content (cigarette vs. pleasant) effects. We compared groups' resting-state connectivity at the network level and for subcortical-cortical pairs. Individuals were clustered based on neuroaffective reactivity to drug-related and pleasant stimuli: The C > P profile showed larger BOLD responses to cigarette cues than to pleasant stimuli, whereas the P > C profile showed the opposite pattern. Whole-brain analyses showed significant Group × Content interactions that mirrored these profiles across left dorsolateral and medial prefrontal cortices and amygdala-hippocampal regions. At rest, individuals in the C > P profile showed weaker within-network connectivity of the frontoparietal control network (FPCN) and, in exploratory analyses, reduced FPCN-nucleus accumbens coupling. By replicating and extending prior psychophysiological work, this study identifies neuroaffective profiles that reflect the variation in incentive salience attribution central to neurobehavioral models of relapse. These findings provide convergent neurobiological markers that characterize distinct motivational pathways in substance use disorders.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70151"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147965213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Study of Plasma NFL and GFAP as Biomarkers of Alcohol Withdrawal-Associated Brain Injury.","authors":"Virgile Clergue-Duval, Frank Questel, Alexandra Dereux, Elodie Bouaziz-Amar, Julien Azuar, Romain Icick, Dorian Rollet, Vanessa Bloch, Jérôme Jeanblanc, Cynthia Marie-Claire, Jean-Louis Laplanche, Frank Bellivier, Claire Paquet, Mickael Naassila, Florence Vorspan","doi":"10.1111/adb.70157","DOIUrl":"10.1111/adb.70157","url":null,"abstract":"<p><p>Plasma neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), tau protein and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are candidate biomarkers of alcohol withdrawal (AW)-associated brain toxicity, as they are biomarkers of axonal, neuronal or glial injury. The aim of this study was to investigate the changes of these biomarkers during AW in patients with severe alcohol use disorder (AUD). Plasma NFL, GFAP, tau and UCHL1 levels were measured, with SIMOA, at three times: on Day 1 (T1), on Day 3 or 4 (T2) and on Day 13, 14 or 15 (T3) of AW. They were analysed with a linear mixed model adjusted for age, sex and body mass index. Changes in these levels according to AW symptom severity were evaluated. Twenty-four inpatients with severe AUD were included: 20 men (83.3%), aged 47.4 years [±11.3], with symptoms requiring a median equivalent-diazepam dose of 0.81 mg/kg at T1. A significant increase was observed for NFL level from T1 to T2 (β = 0.349, p = 0.035), but not for GFAP, tau or UCHL1 levels. In AW symptom severity analyses, a significant positive association was found with equivalent-diazepam dose required × T1-T2 time interaction factor for NFL (β = 0.161, p = 0.028) and for GFAP (β = 0.400, p = 9.9 × 10^-4). This longitudinal study provided preliminary indication that brain injury could occur within the first days of AW, especially in patients with severe pharmacological dependence. Plasma NFL and GFAP are promising biomarkers of AW-related brain pathology and should be investigated as biomarkers of therapeutic response to test innovative drug strategies for preventing this toxicity. Trial Registration: Clinical Trials: NCT05216705.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70157"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Regulates CDK5R1 and NRBP1 to Exert Effects on Alcohol Dependence: Insights From Mendelian Randomization.","authors":"Fuyuan Deng, Junsheng Peng, Siran Lai, Guangpeng Zhang, Miaomiao Li, Yuxin Huang, Mi Yuan, Gaolei Yao, Peiming Zhang, Liming Lu","doi":"10.1111/adb.70162","DOIUrl":"10.1111/adb.70162","url":null,"abstract":"<p><p>Alcohol dependence currently lacks targeted pharmacotherapies, underscoring the urgent need for novel therapeutic targets. Existing research on disease-associated DNA methylation changes and their gene regulatory effects remains inconsistent. To resolve this uncertainty, we applied the Mendelian randomization to elucidate causal mechanisms connecting druggable genes, epigenetic regulation and alcohol dependence development. Integrating MR, colocalization and mediation analyses, we leveraged genome-wide association study (GWAS) (FinnGen), eQTL (eQTLGen) and methylation (GoDMC) data. We assessed causal gene-alcohol dependence relationships, shared causal variants via colocalization and methylation-mediated regulatory mechanisms. Our integrative analysis identified 10 drug-targetable genes showing significant expression alterations in alcohol dependence (FDR < 0.05), with three genes (CDK5R1, CAMKK2 and NRBP1) demonstrating evidence of shared causal variants through colocalization. Epigenetic regulation was particularly evident at two methylation sites (cg07437263 and cg05102552) that indirectly influenced alcohol dependence risk by modulating CDK5R1 (63.92% mediation) and NRBP1 (95.12% mediation) expression. These findings reveal DNA methylation as a critical regulatory mechanism governing neuronal gene expression patterns in alcohol dependence pathogenesis. The strong mediation effects observed for CDK5R1 and NRBP1, coupled with their colocalization evidence, position these genes as promising candidates for both biomarker development and targeted therapeutic interventions in alcohol dependence. This investigation spotlights the regulatory function of DNA methylation on CDK5R1 and NRBP1 in alcohol dependence. It implies that CDK5R1 and NRBP1 could serve as potential clinical biomarkers or therapeutic targets for the early management of alcohol dependence.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70162"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Factors Associated With Spontaneous Remission in Individuals With Alcohol Use Disorder-Results From a Multi-Site Longitudinal Cohort Study.","authors":"Judith Zaiser, Johannes Nitsche, Sabine Hoffmann, Sina Vetter, Nadja Samia Bahr, Clarissa Grundmann, Samanda Krasniqi, Fabian Arntz, Jens Strehle, Michael Marxen, Sabine Vollstädt-Klein, Michael A Rapp, Bernd Lenz, Rainer Spanagel, Michael Smolka, Andreas Heinz, Emanuel Schwarz, Falk Kiefer, Patrick Bach","doi":"10.1111/adb.70153","DOIUrl":"10.1111/adb.70153","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) is considered a chronic disorder with a highly variable course. Understanding this variability is crucial for identifying factors associated with persistence versus spontaneous remission. We analysed data from N = 462 individuals with AUD in an observational longitudinal cohort study to identify factors associated with spontaneous remission. All participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AUD at study entry and were reassessed after 1 year, in which they were classified as being in spontaneous remission (n = 107), falling below the ≥ 2-criteria threshold for AUD (n = 87) or continuing to meet AUD criteria (n = 296). Groups were compared on socio-demographic, clinical and substance use variables at baseline and after 1 year. Additionally, we used machine learning models to identify baseline characteristics predicting a persistent course of AUD. Between-group comparisons revealed that individuals who experienced spontaneous remission reported significantly lower AUD severity (F(2,459) = 25.17, p < 0.001), lower levels of alcohol intake (F(2,459) = 8.31, p = 0.013) and fewer drinking days (F(2,459) = 11.91, p < 0.001) at baseline and after 1 year. Machine learning analysis demonstrated moderate classification performance (AUC = 0.679), with the Alcohol Use Disorders Identification Test (AUDIT) sum score being the most informative predictor for group classification. Our findings indicate significant differences between spontaneously remitted and non-remitted individuals on key alcohol-related variables, supporting the clinical validity of remission as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). In addition, baseline characteristics may help identify individuals at risk of persistent AUD, enabling earlier identification of those who may benefit from specialized treatment. TRIAL REGISTRATION: DRKS number: DRKS00020580.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70153"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Membrane-Centric Plasma Lipidomic Signature of Response to Long-Acting Naltrexone in Alcohol Use Disorder.","authors":"Liyao Huang, Bojie Zhou, Qinling Ou, Jubo Yin, Xiwen Tian, Xuhui Zhou","doi":"10.1111/adb.70165","DOIUrl":"10.1111/adb.70165","url":null,"abstract":"<p><p>Long-acting naltrexone is a first-line pharmacotherapy for alcohol use disorder (AUD), but clinical response is heterogeneous and the underlying biology remains incompletely understood. In a randomised, double-blind, placebo-controlled trial of naltrexone implants (n = 70), the prespecified primary endpoint-percentage of heavy-drinking days (PHDD) over 24 weeks-favoured naltrexone (median 1.49% vs. 13.39%; p = 0.042). In a prespecified Week-12 mechanistic lipidomics substudy, untargeted liquid chromatography-mass spectrometry (LC-MS) profiling was performed in a responder-enriched subset comprising naltrexone responders (RN, n = 18), placebo-treated participants (PL, n = 10) and age- and BMI-matched healthy male controls (HC, n = 10). We derived membrane-related indices reflecting two prespecified axes of phospholipid remodelling: headgroup balance (PC/PE) and acyl-chain composition (arachidonic acid [AA] and n-3 polyunsaturated fatty acids within phospholipid pools). RN showed higher PC/PE and coordinated acyl-chain shifts versus PL, with species-level changes preferentially moving toward the healthy-control direction. Exploratory analyses in naltrexone nonresponders (NR, n = 10) revealed partial Lands-cycle-related shifts but lacked the broader dual-axis configuration observed in RN. In RN + PL (n = 28), higher n-3 in PE and lower AA in PE at Week 12 were prospectively associated with greater subsequent heavy-drinking burden. These findings support a dual-axis membrane remodelling phenotype associated with naltrexone response and prospectively linked to heavy-drinking burden in AUD, providing a biologically grounded framework for future mechanistic and biomarker studies.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70165"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147934672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}