{"title":"The Orexin System Modulates Stress-Induced Alcohol Preference and Reinstatement in Adolescents: Bioinformatics and Experimental Evidence","authors":"Wenhao He, Aqian Hu, Tianshu Zhao, Li Deng, Huilin Wu, Xiaojun Xiang","doi":"10.1111/adb.70173","DOIUrl":"https://doi.org/10.1111/adb.70173","url":null,"abstract":"<p>Underage drinking has become a global public health concern. One of the major causes of underage drinking is stress. The orexin system has been reported to be involved in both alcohol addiction and stress. However, few studies have examined this system, especially among adolescents. Therefore, we constructed protein–protein interaction (PPI) networks to confirm that orexin receptors are connected to stress- and alcohol dependence-related genes, providing a theoretical basis for our experimental approach. Animal experiments employed the conditioned place preference (CPP), the foot-shock stress model and the enzyme-linked immunosorbent assay (ELISA), to elucidate the role of the orexin system in the stress-induced alcohol addiction-related behaviour among adolescent mice. Our results revealed that there were interactions among orexin system, chronic/acute stress and alcohol dependence related proteins. Otherwise, chronic stress can increase the animals' vulnerability to alcohol addition-related behaviour. Additionally, acute foot-shock can promote alcohol-seeking behaviour reinstatement and facilitate orexin concentrations in brain regions that have been shown to be associated with reward and addiction. Moreover, the inhibition of orexin receptors can attenuate the formation and reinstatement of alcohol addiction-like behaviour among adolescent mice. Collectively, our findings indicate that orexin system may be a pivotal target for preventing stress-induced alcohol addiction and reinstatement among the adolescents.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 7","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306187","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}
Andreas Heinz, Selin Icoez, Yvonne Treusch, Gaetano di Chiara, Melissa G. Halil
{"title":"Learning Mechanisms in Alcohol Use Disorders","authors":"Andreas Heinz, Selin Icoez, Yvonne Treusch, Gaetano di Chiara, Melissa G. Halil","doi":"10.1111/adb.70168","DOIUrl":"10.1111/adb.70168","url":null,"abstract":"<p>Pavlovian and operant learning mechanisms promote and maintain alcohol intake despite aversive consequences. Here, we review the evidence for drug-associated modifications of basic learning mechanisms during the initiation and maintenance of alcohol use disorders in humans. We discuss how neuroadaptive effects elicited by chronic alcohol intake in the so-called brain reward system can bias learning and decision making towards drug consumption and contribute to the relapse risk after detoxification. Robustness of results and limitations of the respective neurobiological or imaging techniques are addressed. We opine that studying the effects of alcohol intake on Pavlovian and reinforcement learning can inform psychotherapeutic interventions and help to better understand some new neurobiological interventions. We argue that a focus on drug effects biassing basic learning mechanisms can help to reduce the stigma associated with drug consumption and emphasize behavioural and neurobiological interventions that take individual learning mechanisms into account when promoting alternative coping strategies.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266799","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}
Jennifer J. Barb, Lillian C. King, Alexandria N. Hughes, Jenny Yarmovsky, Nancy Diazgranados, Mehdi Farokhnia, Gwenyth R. Wallen, Melanie Schwandt, Lorenzo Leggio
{"title":"Predicting Outpatient Follow-Up Retention After Inpatient Treatment in Patients With Alcohol Use Disorder: A Data-Driven Random Forest Approach","authors":"Jennifer J. Barb, Lillian C. King, Alexandria N. Hughes, Jenny Yarmovsky, Nancy Diazgranados, Mehdi Farokhnia, Gwenyth R. Wallen, Melanie Schwandt, Lorenzo Leggio","doi":"10.1111/adb.70169","DOIUrl":"https://doi.org/10.1111/adb.70169","url":null,"abstract":"<p>Longer treatment engagement is associated with improved recovery outcomes in alcohol use disorder (AUD), making patient retention a critical determinant of reduced return to drinking. This study aimed to identify factors predicting outpatient treatment engagement, operationalized as the number of follow-up visits, among individuals with AUD following inpatient care. We applied a five-step analytic framework integrating random forest modelling (RFM) and Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify predictors of outpatient visit frequency. Clinical, psychological and physiological variables (<i>n</i> = 177 per participant) collected during inpatient treatment prior to discharge were included. RFM ranked variables associated with follow-up visits, with LASSO used for validation and complementary selection. Over a 5-year period, 119 treatment-seeking patients with AUD (mean age = 45.8) returned for outpatient care, averaging 5.14 visits, following a medical treatment inpatient stay. Positive urgency (VIP = 44.31) and positive life events (VIP = 41.19) emerged as the strongest predictors; both inversely associated with visit frequency. LASSO confirmed positive urgency as a significant predictor (coefficient: −0.03296). Greater alcohol use severity and higher haemoglobin levels were also associated with fewer outpatient visits, whereas higher depressive symptom severity predicted increased follow-up engagement. Using complementary machine learning and regression approaches, this study identified affective traits, alcohol use severity and physiological factors as key determinants of outpatient engagement following inpatient AUD treatment. Interestingly, positive urgency and positive life events, often considered markers of recovery or resilience, were linked to reduced outpatient attendance, suggesting that certain personality or motivational factors may diminish perceived need for continued care. These findings highlight the importance of integrating psychological and motivational variables into postdischarge planning to enhance retention and improve early recovery outcomes.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238077","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":"Correction to “Virtual Reality–Based Cue Exposure and Aversion Therapy for Alcohol Dependence: A Randomized Controlled Trial”","authors":"","doi":"10.1111/adb.70170","DOIUrl":"10.1111/adb.70170","url":null,"abstract":"<p>\u0000 <span>H. Zhao</span>, <span>X. Ying</span>, <span>X. Du</span>, et al., “ <span>Virtual Reality–Based Cue Exposure and Aversion Therapy for Alcohol Dependence: A Randomized Controlled Trial</span>,” <i>Addiction Biology</i> <span>31</span>, no. <span>5</span> (<span>2026</span>): e70166, https://doi.org/10.1111/adb.70166.\u0000 </p><p>In the original publication, the designation of the primary corresponding author was not clearly stated.</p><p>The primary corresponding author of this article is Dan Wang (not Chuansheng Wang). All correspondence regarding this article should be directed to: <span>[email protected]</span>.</p><p>We apologize for this error.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206820","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 Bidirectional Causal Relationships Between Imaging-Derived Brain Phenotypes and Sedative-Hypnotic Use Disorder: A Mendelian Randomization Study","authors":"Liqin Lu, Guoxin Zhuang, Jue Deng, Siheng Huang, Liang Meng, Fenglan Li, Xiaoli Zhu","doi":"10.1111/adb.70160","DOIUrl":"10.1111/adb.70160","url":null,"abstract":"<p>Despite sedative-hypnotic use disorder (SHUD) being a major public health priority due to its high abuse liability, the underlying causal neurobiological mechanisms of individual susceptibility remain largely unknown. We conducted a large-scale, bidirectional two-sample Mendelian randomization (MR) study utilizing genome-wide association study (GWAS) summary statistics for 3935 brain imaging-derived phenotypes (IDPs) from the UK Biobank (<i>N</i> = 33 000 participants) and SHUD data from the FinnGen R10 release (<i>N</i> = 2258 cases). Causal effects were primarily estimated using the inverse-variance weighted (IVW) method, which was supplemented by a suite of sensitivity analyses including MR-Egger, weighted median and MR-PRESSO. Multiple testing was controlled via Benjamini–Hochberg false discovery rate (FDR) correction (<span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mi>q</mi>\u0000 <mo><</mo>\u0000 <mn>0.05</mn>\u0000 </mrow>\u0000 <annotation>$$ q<0.05 $$</annotation>\u0000 </semantics></math>). Forward MR identified 34 brain IDPs with significant causal associations with SHUD risk. Specifically, increased susceptibility was linked to structural metrics in the temporal and limbic regions, including higher cortical thickness in the left transverse temporal sulcus (OR = 1.35, 95% CI 1.09–1.67, FDR = 0.04) and right middle temporal gyrus (OR = 1.30, 95% CI 1.07–1.58, FDR = 0.04), as well as elevated white-to-grey matter intensity contrast in the right insula (OR = 1.31, 95% CI 1.13–1.51, FDR = 0.02) and left parahippocampal gyrus (OR = 1.29, 95% CI 1.08–1.54, FDR = 0.04). Conversely, protective effects were observed for brainstem volume (OR = 0.74, 95% CI 0.61–0.91, FDR = 0.04) and white matter integrity in the left cingulum (OR = 0.73, 95% CI 0.57–0.92, FDR = 0.04). Functional connectivity analyses revealed that higher node activity in the salience network (OR = 0.70, 95% CI 0.53–0.92, FDR = 0.04) and strengthened connectivity between the visual and somatomotor networks (OR range: 0.54–0.74) predicted reduced risk. In contrast, specific edges within the default mode network and visual network were positively associated with SHUD susceptibility (OR = 1.56 and 1.48, respectively). Reverse MR analysis provided limited evidence for a causal effect of genetically predicted SHUD on right middle temporal gyrus thickness. Although a nominal association was observed (OR = 1.03, 95% CI 1.00–1.05, <i>p</i> = 0.02), this finding did not survive multiple testing correction (FDR = 0.56) and lacked robustness across sensitivity models. This research establishes a causal link between SHUD susceptibility and specific cortical morphologies, subcortical volumes and functional network topographies, emphasizing the pivotal roles of the temporal–limbic and salience systems. These findings provide novel mechanistic insights into the neurobiological f","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057543","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}
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