Addiction Biology最新文献

{"title":"Abnormal Cortical Thickness Development in Young Adults With Heavy Cannabis Use: A Longitudinal Study","authors":"Wei Li,&nbsp;Cheng Xu,&nbsp;Hanyuan Xu,&nbsp;Bo Yin,&nbsp;Hui Xu,&nbsp;Dandong Li","doi":"10.1111/adb.70040","DOIUrl":"https://doi.org/10.1111/adb.70040","url":null,"abstract":"<p>Cannabis is one of the most commonly used illicit drugs worldwide, with its prolonged use potentially leading to various cognitive impairments and brain structural changes. However, current research on the dynamic changes in cortical thickness (CT) related to cannabis use remains limited, especially regarding the relationship between the severity of cannabis use and CT changes in heavy cannabis use (HCU). This study employed a longitudinal design to investigate CT changes in young adults with HCU from baseline (BL) to 3-year follow-up (FU). The results showed a significant group effect in the left lateral orbitofrontal cortex (OFC), and a significant time effect revealed CT changes in several brain regions, including the left lateral frontal cortex, bilateral medial frontal cortex, bilateral posterior cingulate cortex and bilateral insula. Simple effects analysis further demonstrated that the CT of left lateral OFC in young adults with HCU decreased significantly at FU compared with their BL and was also lower than control group at FU. Furthermore, a significant positive correlation was observed between the total score of Cannabis Use Disorders Identification Test at FU and the CT of left lateral OFC. These findings suggest that prolonged cannabis use may disrupt the structural integrity of the left lateral OFC, impairing decision-making, impulse control and emotional processing, thereby exacerbating addictive behaviours. This study provides key evidence for understanding the neural mechanisms underlying cannabis addiction.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926017","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":"Reduced Sensitivity to Negative Feedback May Lead to Risky Decision-Making in Amphetamine Users","authors":"Yu-Hua Liu,&nbsp;Chiao-Yun Chen,&nbsp;Neil G. Muggleton","doi":"10.1111/adb.70041","DOIUrl":"https://doi.org/10.1111/adb.70041","url":null,"abstract":"<p>In Taiwan, amphetamines are the main drug of abuse. While drug abuse is often related to individual risky decision-making, how this relates to underlying neural mechanisms in amphetamine abusers remains unclear. The current study was carried out to help better understand this. A Balloon Analogue Risk Task (BART) was used to examine individual risky decision-making in conjunction with event-related potential (ERP) recording and presentation of questionnaires relating to behavioural control. Compared with healthy controls, amphetamine users had a lower score on the Behavioural Inhibition System (BIS) scale and showed reduced amplitudes in feedback-related negativity (FRN) and error-related negativity (ERN) ERP components following negative feedback on the task. Amphetamine users were less sensitive to punitive or aversive stimuli. This reduced sensitivity might lead to a higher tendency for risky decision-making, with them less able to learn from mistakes and thus repeatedly engage in risky behaviours.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909166","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":"Circulating Immune and Endocrine Markers in Currently Drinking and Abstinent Individuals With Alcohol Use Disorder and Controls","authors":"Ryan E. Tyler,&nbsp;Carlotta Vizioli,&nbsp;Jennifer J. Barb,&nbsp;Mehdi Farokhnia,&nbsp;Lorenzo Leggio","doi":"10.1111/adb.70039","DOIUrl":"https://doi.org/10.1111/adb.70039","url":null,"abstract":"<p>Alcohol use disorder (AUD) is associated with changes in endocrine and immune system function. This study is a secondary analysis aimed at investigating changes in circulating immune and endocrine biomarkers in blood samples from three groups: (1) healthy controls (HC, <i>N</i> = 12), (2) AUD—currently drinking, nontreatment seeking (CD, <i>N</i> = 9), and (3) AUD—abstinent, treatment-seeking (AB, <i>N</i> = 10; abstinent for at least 6 weeks). We hypothesized that both immune and endocrine biomarker concentrations would be different in AUD groups compared to healthy controls. Immune biomarkers included IL-8, IL-18, CCL2, TNF-α, IL-1RA, IL-6, and IL-10. Endocrine biomarkers included brain-derived neurotrophic factor (BDNF), glucagon-like peptide 1 (GLP-1), ghrelin, gastric inhibitory peptide (GIP), growth hormone, leptin, and insulin. Biomarker concentrations were compared between the three groups while controlling for age and sex, and associations between biomarker concentrations and behavioral measures were explored. IL-8 concentrations were elevated in AB compared to CD and HC (<i>F</i>(2,29) = 6.33, <i>p</i> = 0.006, ƞ_p² = 0.318). BDNF concentrations were lower in AB compared to HC (<i>F</i>(2,30) = 4.34, <i>p</i> = 0.02, ƞ_p² = 0.266). GLP-1 concentrations were higher in AB compared to HC (<i>F</i>(2,25) = 4.22, <i>p</i> = 0.03, ƞ_p² = 0.287). Exploratory analyses in combined groups showed that measures of past drinking, AUD severity, and anxiety/depression positively correlated with IL-18 and TNF-α and negatively correlated with BDNF. These results demonstrate that circulating concentrations of both immune and endocrine proteins are altered in abstinent individuals with a history of severe AUD (AB group) compared to healthy controls. In contrast, no group differences were observed for any biomarker between the nontreatment seeking, currently drinking people with AUD and the HC group. Our findings highlight the importance of accounting for AUD severity, comorbidities, and treatment-seeking status, especially when studying alcohol-related biomarkers.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896832","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":"Validity Concerns About the Heartbeat Counting Task Extend to Alcohol Use disorder: Evidence From Subclinical and Clinical Samples","authors":"Pauline Billaux,&nbsp;Olivier Desmedt,&nbsp;Olivier Corneille,&nbsp;Olivier Luminet,&nbsp;Mateo Leganes-Fonteneau,&nbsp;Joël Billieux,&nbsp;Pierre Maurage","doi":"10.1111/adb.70032","DOIUrl":"https://doi.org/10.1111/adb.70032","url":null,"abstract":"<p>Theoretical models propose that interoception plays a role in addictive disorder. However, this assumption has been mostly tested using the heartbeat counting task (HCT), which is known to be contaminated by estimation strategies. An adapted version of the HCT (in which respondents report only <i>felt</i> heartbeats) has been developed to reduce estimation biases. Here, we examined the validity of the classical and adapted HCT versions in samples presenting alcohol use disorders. We recruited a clinical sample of 48 patients with severe alcohol use disorder (SAUD), matched with 41 healthy controls (HC), and a subclinical sample of 32 binge drinkers (BD), matched with 30 HC. Participants performed the classical HCT, adapted HCT, and a time estimation task. We additionally assessed mental health variables theoretically related to interoception (alexithymia, anxiety, childhood trauma, depression and emotion regulation). In all groups, HCT scores were smaller in adapted than classical HCT. Patients with SAUD, but not BD, showed lower HCT scores than matched controls, independently of the task. We found no correlation between HCT scores and psychological constructs. Heartbeats reported during classical HCT correlated with seconds reported during time estimation task for SAUD and matched HC, suggesting the use of time estimation strategies to perform the task. The largely reduced HCT performance in the adapted version, the association between HCT performance and time estimation performance and the lack of theoretically expected associations between HCT scores and psychological variables extend doubts on the validity of these tasks for measuring interoceptive accuracy in problematic alcohol consumption.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892876","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":"Acute Alcohol-Induced Changes Measured With Metabotropic Glutamate Receptor 5 Positron Emission Tomography","authors":"Nakul R. Raval,&nbsp;Kelly Smart,&nbsp;Gustavo A. Angarita,&nbsp;Rachel Miller,&nbsp;Yiyun Huang,&nbsp;John H. Krystal,&nbsp;Richard E. Carson,&nbsp;Kelly P. Cosgrove,&nbsp;Stephanie S. O'Malley,&nbsp;Ansel T. Hillmer","doi":"10.1111/adb.70031","DOIUrl":"https://doi.org/10.1111/adb.70031","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alcohol consumption at clinically relevant doses alters brain glutamate release. However, few techniques exist to measure these changes in humans. The metabotropic glutamate receptor 5 (mGluR5) PET radioligand [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 is sensitive to acute alcohol in rodents, possibly mediated by alcohol effects on glutamate release. This study aimed to determine the sensitivity of [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 PET to an acute alcohol challenge in humans.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Eight social drinkers (25–42 years; 5 females) with a recent drinking occasion achieving a blood alcohol level (BAL) &gt; 80 mg/dL were recruited. All participants underwent a 90-min dynamic baseline [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 PET scan. Two weeks later (range: 7–29 days), participants completed an oral laboratory alcohol challenge over 30 min, targeting a BAL of 60 mg/dL. Immediately after the challenge, a second [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 PET scan was performed. Non-displaceable binding potential (&lt;i&gt;BP&lt;/i&gt;&lt;sub&gt;ND&lt;/sub&gt;; indicative of mGluR5 availability) and &lt;i&gt;R&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt; (indicative of relative blood flow) were estimated using the simplified reference tissue model with the cerebellum as the reference region. Blood samples were taken throughout the scanning procedure to measure the BAL.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Seven participants (4 females) completed the study. The mean peak BAL achieved was 61 ± 18 mg/dL. Acute alcohol significantly decreased [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 &lt;i&gt;BP&lt;/i&gt;&lt;sub&gt;ND&lt;/sub&gt;, &lt;i&gt;F&lt;/i&gt;(1, 42) = 17.05, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, Cohen's &lt;i&gt;d&lt;/i&gt; = 0.32–0.60, and increased [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 &lt;i&gt;R&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt;, &lt;i&gt;F&lt;/i&gt;(1, 42) = 6.67, &lt;i&gt;p&lt;/i&gt; = 0.013, Cohen's &lt;i&gt;d&lt;/i&gt; = 0.32–0.48, across brain regions. Exploratory analysis showed a positive relationship between alcohol-induced % change in [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 &lt;i&gt;R&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt; in cortical regions and peak BAL (Spearman rho = 0.78 [frontal cortex] and 0.85 [temporal cortex] = 0.024 and 0.011).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This proof-of-concept study demonstrates that [&lt;sup&gt;11&lt;/sup&gt;C]ABP688 PET imaging is sensitive to the effects of acute alcohol consumption. The observed decrease in mGluR5 availability aligns with preclinical data potentially indicating acute increased extracellular glutamate concentrations following ethanol dosing. This imaging tool could be useful for future investigations into the acute effects of alcohol on the brain during abstinence and withdrawal.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892877","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":"Smoking and High-Altitude Exposure Affect Intrinsic Neural Activity: A fMRI Study of Interactive Effects","authors":"Qingqing Lv,&nbsp;Minghe Wang,&nbsp;Chunxiao Bu,&nbsp;Junjie Liao,&nbsp;Kefan Wang,&nbsp;Hui Xu,&nbsp;Xijuan Liang,&nbsp;Ning Zheng,&nbsp;Liangjie Lin,&nbsp;Longyao Ma,&nbsp;Weijian Wang,&nbsp;Zhen Ma,&nbsp;Meiying Cheng,&nbsp;Xin Zhao,&nbsp;Lin Lu,&nbsp;Yong Zhang","doi":"10.1111/adb.70042","DOIUrl":"https://doi.org/10.1111/adb.70042","url":null,"abstract":"<p>Smoking and high-altitude (HA) exposure both adversely affect human health, with smoking linked to various cancers and high-altitude environments causing physiological and neurological changes. Although the effects of smoking and HA exposure on brain structure and function have been studied separately, their combined impact is still rarely explored. This study aims to investigate the interactive effects of smoking and HA exposure on intrinsic brain activity using the resting-state functional magnetic resonance imaging (rs-fMRI) analysed by the amplitude of low-frequency fluctuations (ALFF) method. We used a mixed sample design, including four groups: (i) HA smokers (<i>n</i> = 22); (ii) HA nonsmokers (<i>n</i> = 22); (iii) sea-level (SL) smokers (<i>n</i> = 26); and (iv) SL nonsmokers (<i>n</i> = 26), for a total of 96 male participants. All subjects underwent resting-state functional magnetic resonance imaging. ALFF was used to assess differences in brain activity among the four groups. Two-way analysis of variance (ANOVA) was conducted to analyse the effects of smoking, high-altitude exposure and their interaction on ALFF. As for the main effect of smoking, elevated ALFF was found in the right superior frontal gyrus, right middle frontal gyrus, right inferior frontal gyrus, right middle cingulate cortex and right precentral gyrus. As for the main effect of HA exposure, elevated ALFF was found in the right putamen, right insula, right inferior frontal gyrus, right middle temporal gyrus, right precentral gyrus, right inferior temporal gyrus and right fusiform. A significant interaction effect between smoking and HA exposure was observed in the right precentral gyrus. Post hoc analysis for the right precentral gyrus showed significantly increased ALFF in groups including HA versus SL smokers; HA versus SL nonsmokers; and HA smokers versus HA nonsmokers. Our findings demonstrate that both smoking and HA exposure independently influence spontaneous brain activity, with a significant interaction between the two factors in modulating brain function. These results offer a neuroimaging-based perspective on substance addiction in high-altitude populations and contribute to a deeper understanding of high-altitude adaptation.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865680","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":"Effectiveness of Disulfiram as Adjunct to Addiction-Focused Treatment for Persons With Severe Alcohol Use Disorder","authors":"Max Schallenberg,&nbsp;Diana Vogel-Blaschka,&nbsp;Maik Spreer,&nbsp;Julia Göstl,&nbsp;Johannes Petzold,&nbsp;Maximilian Pilhatsch","doi":"10.1111/adb.70035","DOIUrl":"https://doi.org/10.1111/adb.70035","url":null,"abstract":"<p>The consumption of alcohol affects 400 million people worldwide, where it is responsible for 7% of deaths. Treatment success rates in this field remain limited. Only 15% of those who need treatment get it. Despite treatment, alcohol intake reoccurs in up to 90% of the cases. The use of disulfiram in preventing alcohol reoccurrence is attributed to its unique mechanism of action as an aversive agent, which causes the patient to experience unpleasant physical symptoms when they consume alcohol. The objective of this study is to confirm and illustrate the efficacy of disulfiram in combination with non-pharmacological intervention for persons with severe AUD. Clinical data from 45 patients of an outpatient treatment programme, including the application of disulfiram (2011–2023) were analysed to assess abstinence rates, craving impact, and demographic factors. Moreover, our analyses aimed to identify predictors and moderators of continuous abstinence duration. The study cohort comprised patients with severe AUD and high rates of comorbidities, the majority of which were affective disorders. During treatment, 50% of patients remained abstinent for at least 1 year. No significant differences were identified in craving, sex or comorbidities compared with those who experienced a return to substance use after treatment initiation. Disulfiram underlined its efficacy and tolerability as an adjunct to addiction-focused treatment in a typical clinical cohort of patients severely affected by AUD. Moreover, our analyses align with previous research indicating that disulfiram appears to allow patients with AUD to resist craving episodes, therefore avoiding impulsive reoccurrences of alcohol intake.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856750","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":"The Impact of Bullying Victimization on Short Video Addiction in Adolescents: The Role of Emotional Distress and Neural Mechanisms","authors":"Qiong Yao,&nbsp;Wenwei Zhu,&nbsp;Yuanyuan Gao,&nbsp;Jinlian Wang,&nbsp;Chang Liu,&nbsp;Guang Zhao,&nbsp;Qiang Wang","doi":"10.1111/adb.70038","DOIUrl":"https://doi.org/10.1111/adb.70038","url":null,"abstract":"<p>Short-video addiction (SVA) has become a growing concern among adolescents. Bullying victimization (BV) is considered a significant factor contributing to it, yet its relationship with SVA remains underexplored. This study investigated the role of BV in SVA, examining developmental and psychological pathways across middle school students (MSS; <i>n</i> = 1269), college students (CS; <i>n</i> = 1615) and a replicated college sample (RCS; <i>n</i> = 112). Descriptive statistics revealed significant correlations between SVA and BV, including subdimensions such as verbal, physical and relational bullying, as well as negative affect (NA). Mediation analyses showed that NA partially mediated the relationship between BV and SVA across both MSS and CS groups, although mediation effects were absent in addicted subgroups, highlighting differing psychological pathways between addicted and nonaddicted populations. Neuroimaging analyses in the RCS sample identified spontaneous functional brain activity linked to SVA in the inferior temporal gyrus (ITG) and parahippocampal gyrus (PHG), with intersubject representational similarity analyses (IS-RSA) further associating PHG and dorsomedial prefrontal cortex (DMPFC) activity patterns with intersubject variations in SVA. These findings underscore bullying victimization as a critical predictor of short video addiction, mediated by NA in nonaddicted groups, and illuminate spontaneous brain activity patterns associated with addiction.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852946","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":"Markers of Negative Emotionality in Individuals With Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder: Role of Childhood Trauma","authors":"E. C. Cullins,&nbsp;T. Gunawan,&nbsp;M. L. Schwandt,&nbsp;J. W. Luk,&nbsp;D. T. George,&nbsp;N. Diazgranados,&nbsp;D. Goldman,&nbsp;V. A. Ramchandani","doi":"10.1111/adb.70037","DOIUrl":"https://doi.org/10.1111/adb.70037","url":null,"abstract":"<p>Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are characterized with heightened negative emotionality (NE) and are frequently comorbid. However, little research has investigated NE in individuals with comorbid AUD/PTSD. We compared psychological and biological markers of NE phenotypes, and alcohol-related outcomes between individuals with AUD with and without PTSD, and healthy controls. Additionally, we evaluated whether childhood trauma severity moderated these relationships. Participants [<i>N</i> = 1292; healthy controls (HC): <i>n</i> = 502 (38.9%); AUD only: <i>n</i> = 610 (47.2%), and AUD/PTSD (CMB); <i>n</i> = 180 (13.9%)] enrolled in the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol underwent clinical, biological and behavioural phenotyping that included psychiatric diagnoses, markers of negative emotionality and allostatic load, alcohol use behaviour, and history of childhood trauma. The CMB group had the most severe alcohol use and childhood trauma history. Psychological NE were the most dysregulated among the CMB group. Biological markers of NE were also dysregulated among the AUD and CMB group, where they displayed greater resting heart rate, diastolic blood pressure and HDL cholesterol relative to HC. Greater childhood trauma severity was associated with greater psychological NE. However, the childhood trauma did not moderate any relationship between diagnosis and NE phenotypes. These results highlight important differences in NE, childhood trauma and alcohol use in individuals with AUD with and without comorbid PTSD. Targeting NE and alcohol-related behaviours is critical in effective treatment of individuals with comorbid AUD/PTSD.</p><p><b>Trial Registration:</b> ClinicalTrials.gov: NCT02231840.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849196","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":"Ibudilast-Mediated Suppression of Neuronal TLR4 in the Prefrontal Cortex Mitigates Methamphetamine-Induced Neuroinflammation and Addictive Behaviours","authors":"Fangmin Wang,&nbsp;Huizhen Liu,&nbsp;Yuting Ke,&nbsp;Xiaolei Huang,&nbsp;Shanshan Chen,&nbsp;Dingding Zhuang,&nbsp;Yiying Zhou,&nbsp;Manqing Wu,&nbsp;Yuting Wang,&nbsp;Miaojun Lai,&nbsp;Huifen Liu,&nbsp;Wenhua Zhou","doi":"10.1111/adb.70033","DOIUrl":"https://doi.org/10.1111/adb.70033","url":null,"abstract":"<p>Methamphetamine (METH) use leads to addiction, neurotoxicity, and neuroinflammation. Ibudilast, a toll-like receptor 4 (TLR4) inhibitor, has been shown to reduce METH-induced neuroinflammation and self-administration, but its specific role in neuronal TLR4 signalling and associated behavioural outcomes remains poorly understood. This study examined Ibudilast's effects on METH reward, drug-seeking behaviour, and TLR4 signalling in a rat self-administration model. Ibudilast was found to dose-dependently reduce METH intake and motivation for the drug, as evidenced by a downward shift in the dose–response curve and a decrease in breakpoint. Additionally, Ibudilast suppressed both cue- and METH priming-induced drug-seeking behaviours. Western blot analysis revealed elevated TLR4, p-NF-κB and IL-6 in the prefrontal cortex after 14 days of METH self-administration. These increases were significantly attenuated by Ibudilast treatment. Furthermore, local administration of Ibudilast in the prefrontal cortex led to a reduction in METH intake and motivation, as well as decreased TLR4 expression in this brain region. Immunofluorescence staining was revealed that TLR4 was expressed predominantly in neurons and microglia, with METH-induced upregulation of neuronal TLR4 being linked to apoptosis. Ibudilast restored normal spatial interactions between neurons and microglia, thereby mitigating neuroinflammation and neuronal damage. Furthermore, local injection of Ibudilast in the prefrontal cortex led to a reduction in METH intake and motivation, as well as decreased expression of TLR4 in the brain region. These findings underscore the critical role of neuronal TLR4 in METH addiction and highlight Ibudilast's therapeutic potential in addressing METH-related neuroinflammation and behavioural dysregulation.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836033","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}