Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex : a comparison between early-onset smokers and late-onset smokers

Funding: This study was supported by the University of St. Andrews Endowment fund.Introduction: The literature suggests that tobacco smoking may have a neurotoxic effect on the developing adolescent brain. Particularly, it may impair the decision-making process of early-onset smokers ( 0.05) in reward-based decision-making were detected between early-onset smokers and late-onset smokers. VBM results revealed early-onset smokers to present lower GM volume in the bilateral anterior insular cortex (AI) in comparison to late-onset smokers and lower WM volume in the right AI in comparison to late-onset smokers. Conclusion: Impairments in reward-based decision-making may not be affected by tobacco smoking initiation during early adolescence. Instead, lower GM and WM volume in the AI of early-onset smokers may underline a vulnerability to develop compulsive tobacco seeking and smoking behavior during adulthood.Publisher PDFPeer reviewe

Neuroanatomical correlates of impulsive choices and risky decision making in young chronic tobacco smokers : a voxel-based morphometry study

This study has been supported by a University of St. Andrews Endowment fund and by a self-funded PhD scholarship.Introduction : Impairments in the multifaceted neuropsychological construct of cognitive impulsivity are a main feature of chronic tobacco smokers. According to the literature, these cognitive impairments are relevant for the initiation andmaintenance of the smoking behavior. However, the neuroanatomical correlates of cognitive impulsivity in chronic smokers remain under-investigated. Methods : A sample of 28 chronic smokers (mean age = 28 years) not affectedby polysubstance dependence and 24 matched non-smoker controls was recruited. Voxel Based Morphometry (VBM) was employed to assess Gray Matter (GM) volume differences between smokers and non-smokers. The relationships between GM volume and behavioral manifestations of impulsive choices (5 trial adjusting delay discounting task, ADT-5) and risky decision making (Cambridge Gambling Task, CGT) were also investigated.  Results : VBM results revealed GM volume reductions in cortical and striatal brainregions of chronic smokers compared to non-smokers. Additionally, smokers showed heightened impulsive choices (p < 0.01, Cohen’s f = 0.50) and a riskier decision- making process (p < 0.01, Cohen’s f = 0.40) compared to non-smokers. GM volume reductions in the left Anterior Cingulate Cortex (ACC) correlated with impaired impulsive and risky choices, while GM volume reductions in the left Ventrolateral Prefrontal Cortex (VLPFC) and Caudate correlated with heightened impulsive choices. Reduced GM volume in the left VLPFC correlated with younger age at smoking initiation (mean = 16 years).  Conclusion : Smokers displayed significant GM volume reductions and related cognitive impulsivity impairments compared to non-smoker individuals. Longitudinal studies would be required to assess whether these impairments underline neurocognitive endophenotypes or if they are a consequence of tobacco exposure on the adolescent brain.Publisher PDFPeer reviewe

Early onset smoking theory of compulsivity development : a neurocognitive model for the development of compulsive tobacco smoking

Funding: This manuscript has been supported by a self-funded PhD scholarship and by a University of St Andrews endowment fund.According to the literature, individuals who start tobacco smoking during adolescence are at greater risk of developing severe tobacco addiction and a heavier smoking behaviour in comparison to individuals who uptake tobacco smoking during subsequent developmental stages. As suggested by animal models, this may be related to the unique neuroadaptive and neurotoxic effects of nicotine on adolescents’ fronto-striatal brain regions modulating cognitive control and impulsivity. Previous research has proposed that these neuroadaptive and neurotoxic effects may cause a heightened reward-oriented impulsive behaviour that may foster smoking relapses during quit attempts. However, developments in the field of Addiction Neuroscience have proposed drug addiction to represent a type of compulsive behaviour characterised by the persistent use of a particular drug despite evident adverse consequences. One brain region that has received increased attention in recent years and that has been proposed to play a central role in modulating such compulsive drug seeking and using behaviour is the insular cortex. Lesion studies have shown that structural damages in the insular cortex may disrupt the smoking behaviour, while neuroimaging studies reported lower Gray Matter volume in the anterior insular cortex of chronic smokers compared to non-smokers, in addition to correlations between Gray Matter volume in the anterior insular cortex and measures of compulsive cigarette smoking. Based on the finding of our recent study reporting early onset smokers (mean age at regular smoking initiation= 13.2 years) to display lower Gray Matter and White Matter volume in the anterior insular cortex compared to late onset smokers (mean age at regular smoking initiation=18.0 years), we propose that the anterior insular cortex may play a central role in mediating the association between smoking uptake during adolescence and smoking heaviness/tobacco addiction during adulthood.Publisher PDFPeer reviewe

Understanding fatal and non-fatal drug overdose risk factors : overdose risk questionnaire pilot study—validation

Data collection and analysis was supported by the Health Informatics Centre, Farr Institute, the University of Dundee. In addition, NHS Fife R&D, NHS Education for Scotland, and the Medical School of the University of St Andrews supported the project.Background: Drug overdoses (fatal and non-fatal) are among the leading causes of death in population with substance use disorders. The aim of the current study was to identify risk factors for fatal and non-fatal drug overdose for predominantly opioid-dependent treatment–seeking population. Methods: Data were collected from 640 adult patients using a self-reported 25-item Overdose Risk (OdRi) questionnaire pertaining to drug use and identified related domains. The exploratory factor analysis (EFA) was primarily used to improve the interpretability of this questionnaire. Two sets of EFA were conducted; in the first set of analysis, all items were included, while in the second set, items related to the experience of overdose were removed. Logistic regression was used for the assessment of latent factors’ association with both fatal and non-fatal overdoses. Results: EFA suggested a three-factor solution accounting for 75 and 97% of the variance for items treated in the first and second sets of analysis, respectively. Factor 1 was common for both sets of EFA analysis, containing six items (Cronbach’s α = 0.70) focusing around “illicit drug use and lack of treatment.” In the first set of analysis, Factors 2 (Cronbach’s α = 0.60) and 3 (Cronbach’s α = 0.34) were focusing around “mental health and emotional trauma” and “chronic drug use and frequent overdose” domains, respectively. The increase of Factor 2 was found to be a risk factor for fatal drug overdose (adjusted coefficient = 1.94, p = 0.038). In the second set of analysis, Factors 2 (Cronbach’s α = 0.65) and 3 (Cronbach’s α = 0.59) as well as Factor 1 were found to be risk factors for non-fatal drug overdose ever occurring. Only Factors 1 and 3 were positively associated with non-fatal overdose (one in a past year). Conclusion: The OdRi tool developed here could be helpful for clinical studies for the overdose risk assessment. However, integrating validated tools for mental health can probably help refining the accuracy of latent variables and the questionnaire’s consistency. Mental health and life stress appear as important predictors of both fatal and non-fatal overdoses.Publisher PDFPeer reviewe

Overdose alert and response technologies : state-of-the-art review

Funding: Technology Enabled Care program of the Scottish Government.Background: Drug overdose deaths, particularly from opioids, are a major global burden, with 128,000 deaths estimated in 2019. Opioid overdoses can be reversed through the timely administration of naloxone but only if responders are able to administer it. There is an emerging body of research and development in technologies that can detect the early signs of an overdose and facilitate timely responses. Objective: Our aim was to identify and classify overdose-specific digital technologies being developed, implemented, and evaluated. Methods: We conducted a “state-of-the-art review.” A systematic search was conducted in MEDLINE, Embase, Web of Science, Scopus, ACM, IEEE Xplore, and SciELO. We also searched references from articles and scanned the gray literature. The search included terms related to telehealth and digital technologies, drugs, and overdose and papers published since 2010. We classified our findings by type of technology and its function, year of publication, country of study, study design, and theme. We performed a thematic analysis to classify the papers according to the main subject. Results: Included in the selection were 17 original research papers, 2 proof-of-concept studies, 4 reviews, 3 US government grant registries, and 6 commercial devices that had not been named in peer-reviewed literature. All articles were published between 2017 and 2022, with a marked increase since 2019. All were based in or referred to the United States or Canada and concerned opioid overdose. In total, 39% (9/23) of the papers either evaluated or described devices designed to monitor vital signs and prompt an alert once a certain threshold indicating a potential overdose has been reached. A total of 43% (10/23) of the papers focused on technologies to alert potential responders to overdoses and facilitate response. In total, 48% (11/23) of the papers and 67% (4/6) of the commercial devices described combined alert and response devices. Sensors monitor a range of vital signs, such as oxygen saturation level, respiratory rate, or movement. Response devices are mostly smartphone apps enabling responders to arrive earlier to an overdose site. Closed-loop devices that can detect an overdose through a sensor and automatically administer naloxone without any external intervention are still in the experimental or proof-of-concept phase. The studies were grouped into 4 themes: acceptability (7/23, 30%), efficacy or effectiveness (5/23, 22%), device use and decision-making (3/23, 13%), and description of devices (6/23, 26%). Conclusions: There has been increasing interest in the research and application of these technologies in recent years. Literature suggests willingness to use these devices by people who use drugs and affected communities. More real-life studies are needed to test the effectiveness of these technologies to adapt them to the different settings and populations that might benefit from them.Publisher PDFPeer reviewe

Protracted abstinence in males with an opioid use disorder : partial recovery of nucleus accumbens function

Opioid use disorder (OUD) affects more than 27 million people globally accounting for more than 300,000 deaths annually. Protracted abstinence among individuals with OUD is rare due to a high relapse rate among those not receiving medications for OUD. Extensive preclinical studies form the basis of the allostasis theory, which proposes long lasting functional brain abnormalities that persist after opioid withdrawal and contribute to relapse. Few studies have tested the allostasis theory in humans using neuroimaging. Here we used fMRI and an instrumental learning task to test allostasis theory predictions (ATP) of functional abnormalities in both positive valence (PVS) and negative valence (NVS) accumbens systems in OUD patients with protracted abstinence (n=15), comparing them with OUD patients receiving methadone treatment (MT) (n=33), and with healthy controls (n=23). As hypothesized, protracted abstinence OUD patients showed incomplete recovery of nucleus accumbens function, as evidenced by blunted response to aversive events (NVS) during negative reinforcement, as observed in MT patients. In contrast, their accumbens response to rewarding events (PVS) during positive reinforcement was similar to that of controls and different to that in MT patients whose response was blunted. Protracted abstinence OUD patients also showed improvements in depression symptoms compared to MT patients. Residual depressive symptoms and pre-MT intravenous drug measures were associated with worse accumbens function in protracted abstinence. These results support the ATP of long lasting dysfunction of NVS after withdrawal and show preliminary evidence of recovery of PVS function with protracted withdrawal. Therapeutic strategies that target NVS may facilitate recovery.Publisher PDFPeer reviewe

Association between chronic psychoactive substances use and systemic inflammation : a systematic review and meta-analysis

This systematic review and meta-analysis assess the change in inflammation biomarkers level among chronic psychoactive substance users. To meet the required inclusion criteria, all studies had to describe human participants with an age ≥18y., experiencing chronic psychostimulant (nicotine, amphetamine, cocaine), sedative (benzodiazepine, opioids) and/or cannabinoid use. The comparison group was defined as healthy participants. Studies where included if they reported at least one of the pro/inflammatory biomarkers. Study bias was examined by Funnel plots and heterogeneity by computing the I2 statistics. Only 21 eligible studies were selected based on 26216 study participants. A small and significant effect size of 0.18mg/L (95% CI:0.10-0.27) was detected in favor of chronic smokers (z=4.33;P<0.0001). There was evidence of publication bias for studies measuring IL-6 and IL-10 association with cocaine and IL-6 in association with cannabis. In summary, except for chronic tobacco users, there was no evidence of association between other chronic substances abuse and inflammatory levels. More studies are needed to inform policy and decision makers about the utility of anti-inflammatory based targeted intervention programs.PostprintPeer reviewe

Rapid opioid overdose response system technologies

Purpose of review  Opioid overdose events are a time sensitive medical emergency, which is often reversible with naloxone administration if detected in time. Many countries are facing rising opioid overdose deaths and have been implementing rapid opioid overdose response Systems (ROORS). We describe how technology is increasingly being used in ROORS design, implementation and delivery. Recent findings  Technology can contribute in significant ways to ROORS design, implementation, and delivery. Artificial intelligence-based modelling and simulations alongside wastewater-based epidemiology can be used to inform policy decisions around naloxone access laws and effective naloxone distribution strategies. Data linkage and machine learning projects can support service delivery organizations to mobilize and distribute community resources in support of ROORS. Digital phenotyping is an advancement in data linkage and machine learning projects, potentially leading to precision overdose responses. At the coalface, opioid overdose detection devices through fixed location or wearable sensors, improved connectivity, smartphone applications and drone-based emergency naloxone delivery all have a role in improving outcomes from opioid overdose. Data driven technologies also have an important role in empowering community responses to opioid overdose. Summary  This review highlights the importance of technology applied to every aspect of ROORS. Key areas of development include the need to protect marginalized groups from algorithmic bias, a better understanding of individual overdose trajectories and new reversal agents and improved drug delivery methods.PostprintPeer reviewe

Comparing neurocognitive function in individuals receiving chronic methadone or buprenorphine for the treatment of opioid dependence : a systematic review

Introduction: Agonist Opioid Treatments (AOT) have been, in comparison to healthy controls, associated with neurocognitive impairment in different domains. This review identifies differences in neurocognitive function as a result of treatment with either buprenorphine or methadone. Method: A qualitative and systematic literature review of published articles from 1946 to 29/2/2016 on neurocognitive function of patients prescribed buprenorphine or methadone and compared with healthy patients utilising the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Results: The limited data demonstrate buprenorphine as presenting with fewer neurocognitive impairments, in cognitiveimpulsivity, cognitive flexibility and attention domains when compared with methadone. However both treatments modalities presented with more impairments in neurocognitive function domains, including short term memory, attention, cognitive flexibility, cognitive impulsivity, motor impulsivity and non planning impulsivity, when compared with healthy control groups. Discussion: The lack of published papers in comparing neurocognitive impairment between the treatment modalities limit interpretation of this systematic review. Conclusion: Further methodologically rigid and higher qualityresearch into the neurocognitive effects of these treatment modalities in the opioid dependent populations, especially when in treatment, is urgently required.Publisher PDFPeer reviewe

Alcohol use disorders in people with intellectual disability

This article initially highlights that although the prevalence of alcohol use disorders in people with intellectual disability (PWID) appears to be low, it is a significant issue. This group can be more vulnerable to the adverse effects of alcohol and it is likely that many PWID who have alcohol use disorders are not being identified. We go on to review the limited existing literature on treatment for PWID who have alcohol use disorders and the challenges in meeting the needs of this patient group. We explore how assessment and treatment of alcohol use disorders in this population can be and needs to be tailored to the needs of PWID on an individual basis. There is also discussion about the use of incapacity legislation to treat this group. LEARNING OBJECTIVES Be aware that alcohol use disorders can be especially problematic for PWID, that such disorders can often go undetected and that adapted screening techniques may be needed to identify such problems Understand the difficulties that this population has in accessing addiction services and that successful management of PWID who misuse alcohol is usually dependent on appropriate joint working between intellectual disability and addiction services Be aware that PWID are not a homogeneous group, rather they vary widely in their abilities, necessitating interventions tailored to the individual, and that the use of compulsory measures to manage PWID who lack capacity regarding to their alcohol use should be done with cautionPostprintPeer reviewe