Addiction Biology最新文献

Agulló, L., Escorial, M., Orutño, S., Muriel, J., Sandoval, J., Margarit, C., & Peiró, A. M. (2024). Epigenetic and Sex Differences in Opioid Use Disorder in Chronic Pain: A Real-World Study Linked With OPRM1 DNA Methylation. Addiction Biology, 29(7), e13422.

The correct name of one of the authors is Samanta Ortuño-Miquel, not Samantha Orutño as it is currently presented.

We apologize for this error.

Repetitive drug use results in enduring structural and functional changes in the brain. Addiction research has consistently revealed significant modifications in key brain networks related to reward, habit, salience, executive function, memory and self-regulation. Techniques like Voxel-based Morphometry have highlighted large-scale structural differences in grey matter across distinct groups. Source-based Morphometry (SBM) takes this a step further by incorporating the Independent Component Analysis to detect shared patterns of grey matter variation, all without requiring prior selection of regions of interest. However, SBM has yet to be employed in the study of structural alteration patterns related to cocaine addiction. Therefore, we performed this analysis to explore alterations in structural covariance specific to cocaine addiction. Our study involved 40 individuals diagnosed with Cocaine Use Disorder (CUD) and 40 matched healthy controls. Participants with CUD completed clinical questionnaires assessing the severity of their dependence and other relevant clinical variables. Following the adjustment for age-related effects, we observed notable disparities between groups in two structural independent components, which we identified as the structural cerebellar network and the structural lateral frontoparietal network, which display opposing trends. Specifically, the individuals with CUD exhibited a heightened contribution to the cerebellar network but simultaneously demonstrated a reduced contribution to the lateral frontoparietal network compared to the healthy controls. These findings unveil distinctive covariance patterns of neuroregulation linked with cocaine addiction, which indicates an interruption in the typical structural development in an affected lateral frontoparietal network, while suggesting an extended pattern of neuroregulation within the cerebellar network in individuals with CUD.

Addictive behaviour is shaped by the dynamic interaction of implicit, bottom-up and explicit, top-down cognitive processes. In alcohol use disorder (AUD), implicit alcohol-related associations have been shown to predict increased subsequent alcohol consumption and are linked to the risk of relapse. Explicit cognitive processes, exerting prefrontal top-down control, are particularly significant during the critical period following the decision to abstain. This study aims to map implicit and explicit cognitive processes in recently abstinent individuals with AUD and to explore the effect of cathodal transcranial direct current stimulation (tDCS) on implicit associations by modulating top-down control. In this preregistered, double-blind, sham-controlled clinical trial, 30 abstinent individuals with AUD participated in two experimental sessions. They received either 2 mA cathodal tDCS to the left dorsolateral prefrontal cortex (dlPFC) or sham tDCS in a crossover design. During tDCS, participants completed the alcohol approach implicit association test (IAT) and the drinking identity IAT, along with two control tasks. Additionally, we collected explicit ratings of the IAT stimuli and assessed craving before and after each experimental session. Preregistered ANOVAs revealed significant implicit alcohol–avoidance and non–drinking identity biases. Cathodal tDCS did not modulate IAT scores. Explicit ratings showed a preference for non-alcoholic drinks and non-drinking identity, correlating moderately with IAT scores. Exploratory analyses indicated that cathodal tDCS mitigated the increase in nicotine craving during the experimental session. This preregistered clinical trial provides robust evidence that single-session cathodal tDCS to the left dorsolateral prefrontal cortex does not modulate implicit associations in AUD, with Bayesian analyses corroborating the absence of tDCS effects. Our results emphasize the impact of contextual factors on the interplay between explicit and implicit cognitive processes and underscore the importance of investigating multisession stimulation paradigms in future research.

One of the many human capabilities acquired during adolescence is the adaptivity in changing environments. In this longitudinal study, we investigated this adaptivity, as measured by probabilistic reversal learning (PReL) tasks, in N = 143 adolescents at ages 14, 16 and 18. Computational modelling and functional magnetic resonance imaging were applied to identify the neurocognitive processes underlying reversal learning and its development. Previous studies have demonstrated a correlation between heavy alcohol use and impaired reversal learning. Our hypothesis was that PReL is negatively associated with current and future alcohol use and that alcohol use impairs PReL by altering neurocognitive processes. Behaviourally, PReL performance improved, which was associated with a lower probability of switching choices and was considered an adaptive process. Computationally, this was accounted for by higher learning rates, enhanced sensitivity to wins and reduced sensitivity to losses in older adolescents. Alcohol consumption increased but remained at a low level for most participants. More risky drinking was associated with less medial frontal activity elicited by reward prediction errors. These findings suggest that reversal learning may be more relevant for the maintenance or escalation of risky than for low-level drinking. Challenges and potential solutions for longitudinal studies such as reliability are discussed.

Despite its widespread use and popularity, cannabis is known to impact higher order cognitive processes such as attention and executive function. However, far less is known about the impact of chronic cannabis use on cognitive flexibility, a component of executive function, and this is especially true for the underlying functional connectivity dynamics. To address this, we enrolled 25 chronic cannabis users and 30 demographically matched non-users who completed an interview probing current and past substance use, a urinalysis to confirm self-reported substance use and a task-switch cognitive paradigm during magnetoencephalography (MEG). Time-frequency windows of interest were identified using a data-driven statistical approach, and spectrally specific neural oscillatory responses were imaged using a beamformer. The resulting maps were grand-averaged across all participants and conditions, and the peak voxels in these maps of neural oscillatory activity were used as seeds to compute connectivity using a whole-brain cortical-coherence approach. Whole-brain neural switch cost connectivity maps were then computed by subtracting the connectivity map for the no-switch condition from that of the switch condition per participant. These switch cost functional connectivity maps were then correlated with the behavioural switch cost per group and probed for group differences in the neuro-behavioural associations. Our behavioural results indicated that all participants had slower reaction times during switch compared to no-switch trials. Regarding the MEG data, cannabis users exhibited altered associations between functional connectivity switch costs and behavioural switch costs along pathways connecting visual cortices and regions in the ventral attention network, within the theta, alpha and gamma frequency ranges. These results indicate modified multispectral associations between functional connectivity and behavioural switch costs among visual cortices and key brain regions underlying executive function in cannabis users.

Alcohol consumption produces acute analgesic effects, and people experiencing pain conditions may drink alcohol to alleviate discomfort. However, tolerance to the analgesic properties of alcohol could prompt escalating consumption and dependence. Both nociception and alcohol-induced analgesia are under significant genetic control. Understanding the genetic architecture of these processes could inform better treatment options for people with pain conditions. This study aims to identify quantitative trait loci (QTL) driving variation in ethanol-induced analgesia across BXD recombinant inbred mouse lines. Male and female mice from 62 BXD strains received ethanol or saline oral gavage for five days and were tested for hot plate (HP) latency at baseline, Day 1 and Day 5. QTL mapping of HP phenotypes identified a significant provisional QTL on chromosome 17 for Day 1 HP latency in mice receiving ethanol. An additional highly suggestive QTL was present on chromosome 9 for the difference in pre- and post-ethanol thermal nociception. Candidate genes within QTL support intervals were provisionally identified using HP phenotypic correlations to transcriptomic database, expression QTL analysis and other bioinformatics inquiries. The combined behavioural and bioinformatic analyses yielded strong ethanol analgesia candidate genes, specifically Myo6. Thus, the results of this genetic study of ethanol-induced analgesia in BXD mouse strains may contribute significantly to our understanding of the molecular basis for individual variation in the analgesic response to acute ethanol.

Drinking as a coping method in response to pain is a complex behaviour, involving multiple neural, motivational, and psychological factors. Among these factors, pain sensitivity and pain-related drinking motive can significantly promote alcohol use. In contrast, proactive avoidance – a beneficial strategy of initiating overt actions to avoid negative outcomes – reduces harmful consumption. Yet, these factors have not been assessed as potential predictors of future drinking behaviour. Here, in a longitudinal study we collected fMRI data in 50 drinkers who, at baseline, performed a probabilistic learning go/nogo task that involved proactive avoidance of painful electric shocks. Pain-related psychological measures and the neural correlates of proactive avoidance were examined in relation to participants' alcohol use and craving in the following 12 months. We found that deficits in proactive avoidance were associated with future drinking severity. Importantly, diminished activation of the dorsal anterior cingulate cortex (dACC) during proactive avoidance also predicted subsequent percentage of heavy drinking days. Using Bayesian network modelling, we established a potential pathway in which drinkers' heightened pain sensitivity led to greater pain-avoidance drinking motive and alcohol craving. Both craving and weakened dACC activation to proactive avoidance predicted higher levels of drinking during the follow-up period. Taken together, our study identified pain sensitivity, pain-avoidance drinking motive, and impaired proactive avoidance as predictors of future alcohol use severity. These findings highlight the roles of pain response, thus potentially informing interventions for individuals at risk of alcohol use disorders.

The relationship between stress, hair cortisol and alcohol consumption has mostly been investigated among clinical and adult study samples, with inconsistent findings. The present study aimed to examine cross-sectional and longitudinal associations between chronic stress, hair cortisol and average past-year alcohol consumption within a population-based sample of adolescents and young adults. At baseline of the epidemiological cohort study, N = 1180 individuals aged 14–21 from Dresden, Germany, were assessed (11/2015–12/2016). A maximum N = 1055 were analysed in cross-sectional analyses and a maximum N = 722 in longitudinal analyses (1-year follow-up). Multivariate linear regression analyses were conducted to reveal cross-sectional associations between perceived chronic stress, hair cortisol concentration and average past-year alcohol consumption in males and females. Longitudinally, weighted linear regression models examined relationships between (a) perceived chronic stress at baseline and altered hair cortisol concentration over 1 year, (b) perceived chronic stress/hair cortisol concentration at baseline and altered average alcohol consumption over 1 year and (c) average past-year alcohol consumption at baseline and altered stress/hair cortisol concentration over 1 year. Cross-sectionally, no significant relationships were found between stress, hair cortisol and average past-year alcohol consumption at baseline. In females, higher baseline perceived chronic stress was associated with an increase in hair cortisol concentration over 1 year, whereas no relationship was found in the cross-sectional analysis between baseline perceived chronic stress and baseline past-year average alcohol consumption. When using hair cortisol as a biomarker for stress perception, the focus of future research should be on potential time lags between perceived chronic stress and hair cortisol increase.

Oligodendrocytes are a key cell type within the central nervous system (CNS) that generates the myelin sheath covering axons, enabling fast propagation of neuronal signals. Alcohol consumption is known to affect oligodendrocytes and white matter in the CNS. However, most studies have focused on foetal alcohol spectrum disorder and severe alcohol use disorder. Additionally, the impact of alcohol dosage on oligodendrocytes has not been previously investigated. In this study, we evaluated transcriptomic changes in C57BL6/J cultured mature oligodendrocytes following exposure to moderate and high concentrations of alcohol. We found that high concentrations of alcohol elicited gene expression changes across a wide range of biological pathways, including myelination, protein translation, integrin signalling, cell cycle regulation and inflammation. Further, our results demonstrate that transcriptomic changes are indeed dependent on alcohol concentration, with moderate and high concentrations of alcohol provoking distinct gene expression profiles. In conclusion, our study demonstrates that alcohol-induced transcriptomic changes in oligodendrocytes are concentration-dependent and may have critical downstream impacts on myelin production. Targeting alcohol-induced changes in cell cycle regulation, integrin signalling, inflammation or protein translation regulation may uncover mechanisms for modulating myelin production or inhibition. Furthermore, gaining a deeper understanding of alcohol's effects on oligodendrocyte demyelination and remyelination could help uncover therapeutic pathways that can be utilized independently of alcohol to aid in remyelinating drug design.