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Contains fulltext : 306496.pdf (Publisher’s version ) (Open Access), Background: Offspring of parents with alcohol use disorder (AUD) are more susceptible to developing AUD, with an estimated heritability of around 50%. Vulnerability to AUD in first-degree relatives is influenced by biological factors, such as spontaneous brain activity, and high-risk psychosocial characteristics. However, existing resting-state EEG studies in AUD offspring have shown inconsistent findings regarding theta, alpha, and beta band frequencies. Additionally, research consistently demonstrates an increased risk of internalizing and externalizing disorders, self-regulation difficulties, and interpersonal issues among AUD offspring. Methods: This study aimed to investigate the absolute power of theta, alpha, and beta frequencies in young adult offspring with a family history of AUD compared to individuals without family history. The psychosocial profiles of the offspring were also examined in relation to individuals without a family history of AUD. Furthermore, the study sought to explore the potential association between differences in frequency bands and psychosocial variables. Resting-state EEG recordings were obtained from 31 young adult healthy offspring of alcohol-dependent individuals and 43 participants with no family history of AUD (age range: 16-25 years). Participants also completed self-report questionnaires assessing anxiety and depressive symptoms, impulsivity, emotion regulation, and social involvement. Results: The results revealed no significant differences in spontaneous brain activity between the offspring and participants without a family history of AUD. However, in terms of psychosocial factors, the offspring exhibited significantly lower social involvement than the control group. Conclusions: This study does not provide evidence suggesting vulnerability in offspring based on differences in spontaneous brain activity. Moreover, this investigation highlights the importance of interventions aimed at enhancing social connections in offsprin, 10 p.

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of ps

INTRODUCTION: There are growing concerns about commonly inflated effect sizes in small neuroimaging studies, yet no study has addressed recalibrating effect size estimates for small samples. To tackle this issue, we propose a hierarchical Bayesian model to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of sampling variance. METHODS: We estimated the effect sizes of case-control differences on brain structural features between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis and non-dependent participants for 21 individual studies (Total cases: 903; Total controls: 996). Then, the study-specific effect sizes were modeled using a hierarchical Bayesian approach in which the parameters of the study-specific effect size distributions were sampled from a higher-order overarching distribution. The posterior distribution of the overarching and study-specific parameters was approximated using the Gibbs sampling method. RESULTS: The results showed shrinkage of the posterior distribution of the study-specific estimates toward the overarching estimates given the original effect sizes observed in individual studies. Differences between the original effect sizes (i.e., Cohen's d) and the point estimate of the posterior distribution ranged from 0 to 0.97. The magnitude of adjustment was negatively correlated with the sample size (r = -0.27, p < 0.001) and positively correlated with empirically estimated sampling variance (r = 0.40, p < 0.001), suggesting studies with smaller samples and larger sampling variance tended to have greater adjustments. DISCUSSION: Our findings demonstrate the utility of the hierarchical Bayesian model in recalibrating single-study effect sizes using information from similar studies. This suggests that Bayesian utilization of existing knowledge can be an effective alternative approach to improve the effect size estimation in individual studies, particularly for those w

01 februari 2023, Item does not contain fulltext, This study investigated the longitudinal bidirectional associations between likeability, popularity, fear of negative evaluation, and social avoidance, to aid in preventing the negative consequences and persistent trajectories of low social status and heightened social anxiety. In total, 1741 adolescents in grades 7-9 participated at 3 yearly waves. A self-report questionnaire measured fear of negative evaluation. Peer nominations assessed likeability, popularity, and social avoidance. Lower popularity predicted more avoidance, and vice versa. More avoidance was related to lower likeability over time. Being less popular and/or more liked by peers, increased fear of negative evaluation. Support for a transactional model between social anxiety and social status was found, but distinguishing different social status and social anxiety components is necessary.

Item does not contain fulltext, The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of ps

Item does not contain fulltext, Rationale: The first COVID-19 lockdown impacted the social life and behaviors of university students, such as alcohol use. While previous studies have reported changes in students' alcohol use during the lockdown, knowledge of risk groups like binge drinkers is limited. Objective: The purpose of this study is to investigate how the first lockdown impacted the alcohol use of university students who were regular binge drinkers before the lockdown. Methods; Cross-sectional data were used to explore self-reported changes in alcohol use and associated psychosocial effects in regular binge drinking versus regular drinking university students (N = 7355) during the first COVID-19 lockdown (Spring 2020) in the Netherlands. Results: University students generally drank less alcohol and reduced binge drinking behaviors during the lockdown. Being a binge drinker who increased/maintained alcohol use, or a regular drinker who increased, was associated with older age, fewer servings of alcohol per week before COVID-19, higher contact with friends, and not living with parents. Among regular binge drinkers, men increased their alcohol use during the lockdown significantly more than women. Among regular drinkers, those with high depressive symptoms and low resilience had increased alcohol use. Conclusions: These findings give insight into significant changes in drinking behaviors among university students during the first COVID-19 lockdown. More importantly, it underscores the need to reckon vulnerable students considering drinking type and associated psychosocial variables for increasing or maintaining higher alcohol use during societal stress periods. In the present study, an unexpected at-risk group emerged among regular drinkers who increased alcohol use during the lockdown in association with their mental state (i.e., depression and resilience). As the COVID-19 pandemic, and the possibility of similar scenarios in the future, is still present in the current student life, specific

Item does not contain fulltext, Background: Cocaine use disorder is associated with cognitive deficits that reflect dysfunctional processing across neural systems. Because there are currently no approved medications, treatment centers provide behavioral interventions that have only short-term efficacy. This suggests that behavioral interventions are not sufficient by themselves to lead to the maintenance of abstinence in patients with cocaine use disorder. Self-control, which includes the regulation of attention, is critical for dealing with many daily challenges that would benefit from medication interventions that can ameliorate cognitive neural disturbances. Methods: To address this important clinical gap, we conducted a randomized, double-blind, placebo-controlled, crossover design study in patients with cocaine use disorder (n = 23) and healthy control participants (n = 28). We assessed the modulatory effects of acute atomoxetine (40 mg) on attention and conflict monitoring and their associated neural activation and connectivity correlates during performance on the Eriksen flanker task. The Eriksen flanker task examines basic attentional processing using congruent stimuli and the effects of conflict monitoring and response inhibition using incongruent stimuli, the latter of which necessitates the executive control of attention. Results: We found that atomoxetine improved task accuracy only in the cocaine group but modulated connectivity within distinct brain networks in both groups during congruent trials. During incongruent trials, the cocaine group showed increased task-related activation in the right inferior frontal and anterior cingulate gyri, as well as greater network connectivity than the control group across treatments. Conclusions: The findings of the current study support a modulatory effect of acute atomoxetine on attention and associated connectivity in cocaine use disorder., 22 augustus 2023, 12 p.

RIVM rapport:Tussen 1984 en 2006 hebben werknemers van Defensie op de zogenoemde POMS(Prepositioned Organizational Materiel Storage)-locaties (Prepositioned Organizational Materiel Storage) in Nederland Amerikaans materieel onderhouden. Hierbij kon chroom-6 vrijkomen, dat vooral in de grondverf van het materieel zat. Chroom-6 heeft schadelijke eigenschappen waardoor mensen ziek kunnen worden als ze eraan worden blootgesteld. De kans om ziek te worden is groter naarmate iemand meer, vaker of langer aan chroom-6 is blootgesteld. In 2018 bracht het RIVM een overzicht uit van de schadelijke gezondheidseffecten en ziekten die kunnen worden veroorzaakt als mensen tijdens hun werk aan chroom-6 blootstaan. Dit overzicht is in 2020 en 2021 geactualiseerd om nieuwe wetenschappelijke kennis mee te nemen. Dit is de derde actualisatie van het overzicht. De kwaliteit en inhoud van de nieuwe studies is met externe experts geëvalueerd. In deze actualisatie worden de eerdere conclusies bevestigd. Er zijn geen nieuwe schadelijke gezondheidseffecten of ziekten in relatie tot blootstelling aan chroom-6 aangetoond. Beroepsmatige blootstelling aan chroom-6 kan de volgende ziekten veroorzaken: longkanker, neus- en neusbijholtekanker, chronische longziekten, chroom-6-gerelateerde allergische astma en rhinitis, allergisch contacteczeem en perforatie van het neustussenschot door chroomzweren. Beroepsmatige blootstelling aan chroom-6 wordt ervan verdacht strottenhoofdkanker en maagkanker te kunnen veroorzaken (wat betekent: er is beperkt wetenschappelijk bewijs). De actuele lijst met ziekten en schadelijke gezondheidseffecten staat op www.rivm.nl/chroom6/ziektelijst., Between 1984 and 2006, Ministry of Defence personnel maintained American equipment at the so-called POMS sites (POMS stands for Prepositioned Organizational Materiel Storage) located in the Netherlands. They may have been exposed at the workplace to chromium-6 which was primarily contained in the primer used to paint the equipment. The risk of developing diseases is greater the more, the more often, and/or the longer a person is exposed. In 2018, RIVM published an overview of the health effects and diseases which can be caused by chromium-6. This overview has been updated in 2020 and 2021 to include the latest scientific knowledge. This is the third update. The quality and findings of the relevant new studies are evaluated in consultation with external experts. This update confirms the previous conclusions. New scientific studies do not provide evidence for additional adverse health effects in relation to chromium-6 exposure. Exposure to chromium-6 at the workplace may cause the following diseases: lung cancer, nasal and paranasal sinus cancer, chronic lung diseases, chromium-6-related allergic asthma and rhinitis, allergic contact dermatitis and perforation of the nasal septum due to chromium ulcers. Chromium-6 is suspected to cause laryngeal cancer and stomach cancer in humans (which means: there is limited evidence). The current list of diseases and adverse health effects can be found at https://www.rivm.nl/en/chromium-vi-carc.

The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of “New Approach Methodologies” (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure–activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today’s regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free “Next Generation Risk Assessment” (NGRA).

Item does not contain fulltext, Background: Nicotine and illicit stimulants are very addictive substances. Although associations between grey matter and dependence on stimulants have been frequently reported, white matter correlates have received less attention. Methods: Eleven international sites ascribed to the ENIGMA-Addiction consortium contributed data from individuals with dependence on cocaine (n = 147), methamphetamine (n = 132) and nicotine (n = 189), as well as non-dependent controls (n = 333). We compared the fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) of 20 bilateral tracts. Also, we compared the performance of various machine learning algorithms in deriving brain-based classifications on stimulant dependence. Results: The cocaine and methamphetamine groups had lower regional FA and higher RD in several association, commissural, and projection white matter tracts. The methamphetamine dependent group additionally showed lower regional AD. The nicotine group had lower FA and higher RD limited to the anterior limb of the internal capsule. The best performing machine learning algorithm was the support vector machine (SVM). The SVM successfully classified individuals with dependence on cocaine (AUC = 0.70, p < 0.001) and methamphetamine (AUC = 0.71, p < 0.001) relative to non-dependent controls. Classifications related to nicotine dependence proved modest (AUC = 0.62, p = 0.014). Conclusions: Stimulant dependence was related to FA disturbances within tracts consistent with a role in addiction. The multivariate pattern of white matter differences proved sufficient to identify individuals with stimulant dependence, particularly for cocaine and methamphetamine.

Item does not contain fulltext, Reduced anticipatory reward-related activity, especially in the ventral striatum (VS), may underly adolescent vulnerability to develop nicotine dependence. It remains unclear whether nicotine uptake caused by environmental tobacco smoke (ETS) exposure, known to be associated with future smoking, might prompt similar changes in the brain's reward system, rendering adolescents vulnerable for development of nicotine dependence. To address this question, we tested whether current ETS exposure and monthly smoking are associated with VS hypoactivity for non-drug rewards in experimental smoking adolescents. One-hundred adolescents performed a monetary incentive delay task while brain activity was measured using fMRI. To test the hypothesized relationship, we used a variety of approaches: (1) a whole-brain voxel-wise approach, (2) an region-of-interest approach in the VS using frequentist and Bayesian statistics and (3) a small volume voxel-wise approach across the complete striatum. The results converged in revealing no significant relationships between monthly smoking, ETS exposure and reward-related brain activation across the brain or in the (ventral) striatum specifically. However, Bayesian statistics showed only anecdotal evidence for the null hypothesis in the VS, providing limited insight into the (non-)existence of the hypothesized relationship. Based on these results, we speculate that blunted VS reward-related activity might only occur after relatively high levels of exposure or might be associated with more long term effects of smoking. Future studies would benefit from even larger sample sizes to reliably distinguish between the null and alternative models, as well as more objective measures of (environmental) smoking via using devices such as silicone wristbands.

Contains fulltext : 227140.pdf (publisher's version ) (Open Access), The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.

Contains fulltext : 248974.pdf (Publisher’s version ) (Open Access)

18 april 2022, Contains fulltext : 248766.pdf (Publisher’s version ) (Open Access), This pre-registered study focused on developing a new social picture task to assess interpretation bias related to social fears in adolescents. Using such a pictorial task may increase ecological validity and readily trigger emotional processes compared to more traditional verbal tasks that are often used. In the picture task, ambiguous social pictures were presented, followed by a positive and negative interpretation. In this study, we examined how the new task relates to an already existing interpretation bias task and how the new pictorial task relates to social fears in adolescents. The sample consisted of 329 adolescents aged 12 to 18 years. Interpretation bias was assessed with the newly developed pictorial task and with more traditional verbal vignettes. Social fears were measured with self-report questionnaires. The results suggest that the pictorial task was able to assess interpretation bias comparable to the verbal vignettes, suggesting appropriate convergent validity. Interpretation bias assessed with the picture task was linked to higher levels of fear of negative evaluation, the core symptom of social anxiety, but not to social anxiety symptoms in general. The verbal task was linked to both social fears and thus still seems the preferred method to investigate interpretation bias related to social fears in adolescents. However, we do believe that with further improvement of the pictorial task, it could be a useful addition to the research field.

13 mei 2022, Contains fulltext : 250281.pdf (Publisher’s version ) (Open Access), Background: Cognitive biases are found to play a role in the onset and maintenance of social anxiety. However, particularly in adolescence, the link between different biases and their role in predicting social anxiety is far from clear. This study therefore investigated the interplay between attention bias and interpretation bias in relation to social anxiety in adolescence across three years. Methods: 816 adolescents in grade 7 to 9 participated at three yearly waves (52.8% boys, M age grade7 = 12.60). Social anxiety was measured with a self-report questionnaire. Attention bias was measured with a visual search task with emotional faces. Textual vignettes assessed interpretation bias. Results: Cross-lagged models showed that negative interpretation bias at grade 7 predicted an increase in social anxiety at grade 8. This effect was not found from grade 8 to 9. Attention bias did not predict social anxiety. Attention bias and interpretation bias were not longitudinally related to each other, nor did they interact with each other in predicting social anxiety. Conclusions: Thus, no evidence was found for the Combined Cognitive Bias Hypothesis in social anxiety in adolescents. Instead, our results suggest that interpretation bias rather than attention bias contributes to the increase of social anxiety over time.

16 mei 2022, Item does not contain fulltext

Contains fulltext : 244352.pdf (Publisher’s version ) (Open Access), Tobacco, alcohol and cannabis are commonly used among university students. However, student lives and their substance use have changed dramatically since the start of the COVID-19 pandemic. This study investigated the impact of COVID-19 on (trends in) weekly smoking, weekly binge drinking and weekly cannabis use in Dutch university students and investigated associated student-, study- and COVID-19-related characteristics. Between April and June 2020, several Dutch higher educational institutes invited their students to participate in an online survey. Data of 9967 students (Mage = 22.0 (SD = 2.6); Nfemale = 7008 (70.3%)) were available for analyses. Overall, weekly smoking remained stable (±11.5%), weekly binge drinking decreased (from 27.8% to 13.9%) and weekly cannabis use increased (from 6.7% to 8.6%). Male gender, not living with parents, being a bachelor student, having less financial resources and less adherence to the COVID-19 measures were found to increase the risk of substance use (before/during the first COVID-19 lockdown). Additionally, male gender, not living with parents, being a bachelor student, not being born in the Netherlands and having a student loan contributed to the likelihood of increased substance use during COVID-19. Patterns of characteristics contributing to the likelihood of decreased weekly substance use during COVID-19 were less clear. The risk factors male gender, not living with parents and being a bachelor student do not only contribute to the likelihood of using substances but also contribute to the likelihood of increased use during a lockdown. Prevention and intervention programs should especially target these risk groups.

Contains fulltext : 226131.pdf (publisher's version ) (Open Access), To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega‐analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case‐ and control‐only sites led to the inadvertent learning of site‐effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary‐based feature selection leveraging leave‐one‐site‐out cross‐validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test‐set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi‐site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.

Contains fulltext : 230060.pdf (Publisher’s version ) (Closed access), Many American and Dutch adolescents use marijuana regularly. There is concern that such use may impair cognitive function more in adolescents than adults. We examined effects of regular marijuana use on long-term memory and perseveration among American and Dutch adolescents. We administered Buschke's Selective Reminding Test (BSRT) to assess long-term memory and the Wisconsin Card Sorting Test (WCST) to assess perseveration in male teenagers. Usable test data were obtained for 12 American marijuana users, 13 American controls, 9 Dutch marijuana users, and 12 Dutch controls. In BSRT, users showed lower overall long-term storage than controls (adjusted means ± SE's for numbers of words per trial of 9.4 ± 0.2, 13.4 ± 0.3, 11.7 ± 0.2, and 12.4 ± 0.2 for American users, Dutch users, American controls, and Dutch controls, respectively). Marijuana was associated with memory effects only in American, not Dutch, users. Bivariate Pearson correlations for American and Dutch users combined showed associations of lower total recall with more uses in the previous year and lifetime (r = -0.61 and r = -0.53, respectively); and more perseverative errors with more uses in the previous year (r = 0.55). Some findings were consistent with the possibility that regular adolescent marijuana use causes deficits in cognition, especially memory. However, a causal interpretation cannot be inferred from our findings and is challenging to reconcile with the observation of memory deficits only in American users. Our study was novel in examining the influence of nationality on marijuana's cognitive effects. More studies of this topic should compare effects across nationalities or cultures.

Contains fulltext : 241572.pdf (Publisher’s version ) (Closed access), Background and aims: Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol. Design: Cross-sectional sample of adults and a cohort of adolescents. Correlation matrices for cortical thicknesses across 68 regions were summarized with graph theoretic metrics. Setting and participants: 745 adults with AD and 979 non-dependent controls from 24 sites curated by the ENIGMA-Addiction working group, and 297 hazardous drinking adolescents and 594 controls at age 14 and 19 from the IMAGEN study, all from Europe. Measurements: Metrics of network segregation (modularity, clustering coefficient, and local efficiency) and integration (average shortest path length and global efficiency). Findings: The younger AD adults had lower network segregation and higher integration relative to non-dependent controls. Compared with controls, the hazardous drinkers at age 19 showed lower modularity (Area-under-the-curve [AUC] difference = -0.0142, confidence interval [CI] 95% [-0.1333, 0.0092]; p-value = 0.017), clustering coefficient (AUC difference = -0.0164 CI 95% [-0.1456, 0.0043], p-value = 0.008), and local efficiency (AUC difference = -0.0141 CI 95% [-0.0097, 0.0034], p-value = 0.010), as well as lower average shortest path length (AUC difference = -0.0405 CI 95% [-0.0392, 0.0096]; p-value = 0.021) and higher global efficiency (AUC difference = 0.0044 CI 95% [-0.0011, 0.0043]; p-value = 0.023). The same pattern was present at age 14 with lower clustering coefficient (AUC difference = -0.0131 CI 95% [-0.1304, 0.0033]; p-value = 0.024), lower average shortest path length (AUC difference = -0.0362 CI 95% [-0.0334, 0.0118]; p-value = 0.019), and higher global efficiency (AUC difference = 0.0035 CI 95% [-0.0011, 0.0038]; p

Contains fulltext : 248974.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 234454.pdf (Publisher’s version ) (Open Access), Background: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. Method: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

Radboud University, 02 december 2022, Promotores : Otten, R., Kleinjan, M. Co-promotor : Luijten, M., Contains fulltext : 284938.pdf (Publisher’s version ) (Open Access)

Radboud University, 20 december 2022, Promotor : Becker, E.S. Co-promotores : Lange, W.G., Luijten, M., Contains fulltext : 284212.pdf (Publisher’s version ) (Open Access), Social anxiety is common in adolescents and is characterised by the extreme and persistent fear of social situations and negative evaluation by others. The aim of this dissertation was to better understand which factors contribute to the development of social anxiety in adolescence. Specifically, two risk factors were investigated: cognitive biases (divided into 'attention bias' –where you focus your attention on in social situations; and into 'interpretation bias' - how you interpret these situations) and social status (how liked and how popular you are perceived by classmates). This dissertation shows that youth who are less liked and popular and who tend to interpret social situations in a negative way, have an increased risk of developing social anxiety. Preventions for social anxiety should therefore focus on these factors. The role of attention bias in social anxiety was not confirmed in this study.

BACKGROUND AND AIMS: Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy-drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol. DESIGN: Cross-sectional sample of adults and a cohort of adolescents. Correlation matrices for cortical thicknesses across 68 regions were summarized with graph theoretic metrics. SETTING AND PARTICIPANTS: A total of 745 adults with AD and 979 non-dependent controls from 24 sites curated by the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA)-Addiction consortium, and 297 hazardous drinking adolescents and 594 controls at ages 19 and 14 from the IMAGEN study, all from Europe. MEASUREMENTS: Metrics of network segregation (modularity, clustering coefficient and local efficiency) and integration (average shortest path length and global efficiency). FINDINGS: The younger AD adults had lower network segregation and higher integration relative to non-dependent controls. Compared with controls, the hazardous drinkers at age 19 showed lower modularity [area-under-the-curve (AUC) difference = -0.0142, 95% confidence interval (CI) = -0.1333, 0.0092; P-value = 0.017], clustering coefficient (AUC difference = -0.0164, 95% CI = -0.1456, 0.0043; P-value = 0.008) and local efficiency (AUC difference = -0.0141, 95% CI = -0.0097, 0.0034; P-value = 0.010), as well as lower average shortest path length (AUC difference = -0.0405, 95% CI = -0.0392, 0.0096; P-value = 0.021) and higher global efficiency (AUC difference = 0.0044, 95% CI = -0.0011, 0.0043; P-value = 0.023). The same pattern was present at age 14 with lower clustering coefficient (AUC difference = -0.0131, 95% CI = -0.1304, 0.0033; P-value = 0.024), lower average shortest path length (AUC difference = -0.0362, 95% CI = -0.0334, 0.0118; P-value = 0.019) and higher glo

Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites).In total 2088 urine samples were collected from 1050 participants (525 parent-child pairs) and analyzed through harmonized suspect screening by five different laboratories. Fourty pesticide biomarkers (either pesticide metabolites or the parent pesticides as such) relating to 29 pesticides were identified at high levels of confidence in samples across all study sites. Most frequently detected were biomarkers related to the parent pesticides acetamiprid and chlorpropham. Other biomarkers with high detection rates in at least four countries related to the parent pesticides boscalid, fludioxonil, pirimiphos-methyl, pyrimethanil, clothianidin, fluazifop and propamocarb. In 84% of the samples at least two different pesticides were detected. The median number of detected pesticides in the urine samples was 3, and the maximum was 13 pesticides detected in a single sample. The most frequently co-occurring substances were acetamiprid with chlorpropham (in 62 urine samples), and acetamiprid with tebuconazole (30 samples). Some variation in the probability of detection of pesticides (-metabolites) was observed with living in an agricultural area or season of urine sampling, though no consistent patterns were observed. We did observe differences in the probability of detection of a pesticide (metabolite) among children compared to adults, suggesting a different exposure and/or elimination patterns between

While human regulatory risk assessment (RA) still largely relies on animal studies, new approach methodologies (NAMs) based on in vitro, in silico or non-mammalian alternative models are increasingly used to evaluate chemical hazards. Moreover, human epidemiological studies with biomarkers of effect (BoE) also play an invaluable role in identifying health effects associated with chemical exposures. To move towards the next generation risk assessment (NGRA), it is therefore crucial to establish bridges between NAMs and standard approaches, and to establish processes for increasing mechanistically-based biological plausibility in human studies. The Adverse Outcome Pathway (AOP) framework constitutes an important tool to address these needs but, despite a significant increase in knowledge and awareness, the use of AOPs in chemical RA remains limited. The objective of this paper is to address issues related to using AOPs in a regulatory context from various perspectives as it was discussed in a workshop organized within the European Union partnerships HBM4EU and PARC in spring 2022. The paper presents examples where the AOP framework has been proven useful for the human RA process, particularly in hazard prioritization and characterization, in integrated approaches to testing and assessment (IATA), and in the identification and validation of BoE in epidemiological studies. Nevertheless, several limitations were identified that hinder the optimal usability and acceptance of AOPs by the regulatory community including the lack of quantitative information on response-response relationships and of efficient ways to map chemical data (exposure and toxicity) onto AOPs. The paper summarizes suggestions, ongoing initiatives and third-party tools that may help to overcome these obstacles and thus assure better implementation of AOPs in the NGRA.

Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N=2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n=498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in-vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides.For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure.