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

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

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

Relationship Between Cardiovascular Disease Pathology and Fatal Opioid and Other Sedative Overdose:A Post-Mortem Investigation and Pilot Study

Introduction: In 2019, Scotland reported the highest number of drug deaths amongst EU countries. Of the 1,264 drug deaths reported in 2019, 94% were related to polysedative use. Studies have proposed a relationship between opioid use and cardiovascular disease. Furthermore, the concomitant use of sedatives and opioids has been associated with lethal cardiopulmonary events. However, evidence is still limited for the relationship between polysedative use and cardiovascular diseases. Thus, the present study aimed to investigate the association between polysedative use and the underlying cardiovascular pathologies in drug deaths. Methods: This study consisted of a post-mortem investigation of 436 drug deaths. Data extracted from post-mortem reports included socio-demographic characteristics (e.g., gender, age), cardiovascular pathologies (e.g., atherosclerosis, atheroma, and inflammation), in addition to the presence of opioids (e.g. methadone, heroin) and other substances (e.g., alcohol, benzodiazepine) in the blood of the deceased. Stepwise multiple regression models were employed to identify which substances predicted cardiovascular pathologies. Results: The presence of opioids, benzodiazepines, and alcohol in the blood of the deceased predicted overall cardiovascular disease (CVD) severity [R2 = 0.33, F (5, 430) = 39.64, p < 0.0001; adjusted R2 = 0.32, f2 = 0.49]. Positive Beta coefficients may indicate an exacerbation of CVD (B = 0.48 95% CI = 0.25, 0.70) due to the presence of opioids in the blood of the deceased. Negative associations may instead indicate a relative protective effect of alcohol (B = −0.2, 95% CI = −0.41, −0.00) and benzodiazepines (B = −0.29, 95% CI = −0.48, −0.09) on CVD. Conclusion: These findings may inform national clinical guidelines on the need to monitor individuals who abuse opioids for presence of cardiovascular disease risk factors pathologies and provide timely interventions to reduce mortality in the population.Publisher PDFPeer reviewe

World Addiction Medicine Reports : formation of the International Society of Addiction Medicine (ISAM) Global Expert Network (ISAM-GEN) and Its global surveys

Funding: All the infrastructure funding of this initiative is supported by the International Society of Addiction Medicine (ISAM). We will be open to fundraising for specific projects within the platform and future collaboration with external partners.Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.Peer reviewe

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease