Screen use and internet addiction among parents of young children: A nationwide Canadian cross-sectional survey.

OBJECTIVES: To establish the factorial structure and internal consistency of the Internet Addiction Test (IAT) in parents, the level and correlates of problematic internet use, and patterns and types of screen use. STUDY DESIGN: Data were collected through an online questionnaire about preconception health among Canadian women and men with ≥1 child. The questionnaire included the IAT and questions about time spent on screens by device type, use of screens during meals and in the bedroom, and perceptions of overuse. Factor analysis was completed to determine the factorial structure of the IAT, with multivariable linear regression used to determine correlates of the IAT. RESULTS: The sample included 1,156 respondents (mean age: 34.3 years; 83.1% female). The IAT had two factors: "impairment in time management" and "impairment in socio-emotional functioning" of which respondents had more impairment in time management than socio-emotional functioning. Based on the original IAT, 19.4% of respondents would be classified as having a mild internet use problem with 3.0% having a moderate or severe issue. In the multivariable model, perceived stress (b = .28, SE = .05, p < .001) and depressive symptoms (b = .24, SE = .10, p = .017) were associated with higher IAT scores. Handheld mobile devices were the most common type of screen used (mean = 3 hours/day) followed by watching television (mean = 2 hours/day). CONCLUSION: Parents spent a significant portion of their time each day using screens, particularly handheld mobile devices. The disruption caused by mobile devices may hinder opportunities for positive parent-child interactions, demonstrating the need for resources to support parents ever-growing use of technologies.

The contributions of social comparison to social network site addiction.

Excessive use of social network sites (SNSs) can often lead to negative consequences of frequent upward social comparisons despite having the social network platform to present users in a favorable light. However, the existing literature gives little evidence to social comparison related antecedents and consequents of uncontrollable use of SNSs. The present study aimed to investigate the contributions of social comparison to SNS addiction. In Study 1, using a convenient sample in Austria (n = 103), we showed that the tendency to engage in social comparisons of ability (but not of opinion) predicted self-reported SNS addiction over and above the feelings of relative deprivation on social support and status. SNS addiction mediated the relations between social comparison of ability and stress, but not self-esteem. In Study 2, using a broad sample of participants in Austria (n = 500), we replicated the findings observed in Study 1 and showed that contrastive upward social comparison emotions (i.e., envy, depression) mediated the relation between SNS addiction and lower self-esteem whereas the contrastive downward social comparison emotion (i.e., contentment) mediated the relation between SNS addiction and higher self-esteem. Our findings suggest that SNS addiction closely relates to psychological constructs relevant to social comparison, mediates the link between social comparison of ability and detrimental consequences (i.e., stress, well-being) and demonstrate how social comparison emotions relate to both positive and negative associations between SNS addiction and self-esteem.

Addiction-Associated Genetic Variants Implicate Brain Cell Type- and Region-Specific Cis-Regulatory Elements in Addiction Neurobiology.

Recent large genome-wide association studies have identified multiple confident risk loci linked to addiction-associated behavioral traits. Most genetic variants linked to addiction-associated traits lie in noncoding regions of the genome, likely disrupting cis-regulatory element (CRE) function. CREs tend to be highly cell type-specific and may contribute to the functional development of the neural circuits underlying addiction. Yet, a systematic approach for predicting the impact of risk variants on the CREs of specific cell populations is lacking. To dissect the cell types and brain regions underlying addiction-associated traits, we applied stratified linkage disequilibrium score regression to compare genome-wide association studies to genomic regions collected from human and mouse assays for open chromatin, which is associated with CRE activity. We found enrichment of addiction-associated variants in putative CREs marked by open chromatin in neuronal (NeuN+) nuclei collected from multiple prefrontal cortical areas and striatal regions known to play major roles in reward and addiction. To further dissect the cell type-specific basis of addiction-associated traits, we also identified enrichments in human orthologs of open chromatin regions of female and male mouse neuronal subtypes: cortical excitatory, D1, D2, and PV. Last, we developed machine learning models to predict mouse cell type-specific open chromatin, enabling us to further categorize human NeuN+ open chromatin regions into cortical excitatory or striatal D1 and D2 neurons and predict the functional impact of addiction-associated genetic variants. Our results suggest that different neuronal subtypes within the reward system play distinct roles in the variety of traits that contribute to addiction.SIGNIFICANCE STATEMENT We combine statistical genetic and machine learning techniques to find that the predisposition to for nicotine, alcohol, and cannabis use behaviors can be partially explained by genetic variants in conserved regulatory elements within specific brain regions and neuronal subtypes of the reward system. Our computational framework can flexibly integrate open chromatin data across species to screen for putative causal variants in a cell type- and tissue-specific manner for numerous complex traits.

Regional gray matter volume associated with exercise dependence: A voxel-based morphometry study.

Although regular physical exercise has multiple positive benefits for the general population, excessive exercise may lead to exercise dependence (EXD), which is harmful to one's physical and mental health. Increasing evidence suggests that stress is a potential risk factor for the onset and development of EXD. However, little is known about the neural substrates of EXD and the underlying neuropsychological mechanism by which stress affects EXD. Herein, we investigate these issues in 86 individuals who exercise regularly by estimating their cortical gray matter volume (GMV) utilizing a voxel-based morphometry method based on structural magnetic resonance imaging. Whole-brain correlation analyses and prediction analyses showed negative relationships between EXD and GMV of the right orbitofrontal cortex (OFC), left subgenual cingulate gyrus (sgCG), and left inferior parietal lobe (IPL). Furthermore, mediation analyses found that the GMV of the right OFC was an important mediator between stress and EXD. Importantly, these results remained significant even when adjusting for sex, age, body mass index, family socioeconomic status, general intelligence and total intracranial volume, as well as depression and anxiety. Collectively, the results of the present study provide crucial evidence of the neuroanatomical basis of EXD and reveal a potential neuropsychological pathway in predicting EXD in which GMV mediates the relationship between stress and EXD.

Dorsal and ventral striatum activity in individuals with buying-shopping disorder during cue-exposure: A functional magnetic resonance imaging study.

BACKGROUND AND AIMS: Buying-shopping disorder (BSD) is a clinical condition in which individuals lose control over their buying behaviour and continue buying despite negative consequences such as indebtedness, loss of family and friends. BSD has been considered a behavioural addiction and first studies provide evidence for cue-reactivity and craving as potential pathomechanisms. The current study aimed at investigating neural correlates of cue-reactivity and craving in individuals with BSD using functional magnetic resonance imaging (fMRI). METHODS: A cue-reactivity paradigm comprising individualised shopping-related and control cues was applied in n = 18 individuals diagnosed with BSD and n = 18 gender, age, and handedness matched control participants using fMRI. Outside the scanner, symptoms of BSD and craving reactions towards shopping (before and after the cue-reactivity paradigm) were assessed via questionnaires. FINDINGS: Higher subjective craving reactions towards shopping, prior and after exposure to shopping cues, were observed in individuals with BSD compared to control participants. Consistent with studies in addiction research, we found increased activations in the dorsal striatum for individuals with BSD compared to control participants during exposure to shopping cues. Activity in the ventral striatum was associated with symptoms of BSD in affected individuals, but not in control participants. CONCLUSIONS: Consistent with studies investigating cue-reactivity in substance-use and behavioural addictions, the association between cue-exposure and activities in reward-related brain structures such as the dorsal and ventral striatum in BSD participants may contribute to a neural explanation of why individuals experience irresistible urges to buy and lose control over their behaviour.

Smartphone use patterns and problematic smartphone use among preschool children.

BACKGROUND: The purpose of the present study was to identify smartphone use patterns associated with problematic smartphone use (PSU) among preschool children. Little is known about PSU patterns in younger children, although the age for first smartphone use is decreasing. METHODS: We applied a cross-sectional study design to analyze data obtained from a nationwide survey on smartphone overdependence conducted in 2017 by the South Korean Ministry of Science and ICT and the National Information Society Agency. Data from 1,378 preschool children were analyzed using binomial logistic regression analysis. This study was conducted in compliance with STROBE (Strengthening the Reporting of Observational Studies in Epidemiology). RESULTS: Seventeen percent of the sample met the criteria for PSU. The odds of PSU significantly increased with frequent smartphone use and in children who used a smartphone for more than two hours per day. Using smartphones to watch TV shows or videos for entertainment or fun significantly increased the odds of PSU, whereas using smartphones for education, games, and social networking did not. CONCLUSIONS: The findings indicate that one of five preschool children using smartphones could experience PSU. Compared to other age groups, PSU in young children may be more associated with their caregivers. To prevent PSU in preschool children, caregivers need information about the total screen time recommended for children, smartphone use patterns associated with PSU, suggestions for other activities as possible alternatives to smartphone use, and strategies to strengthen children's self-regulation with regards to smartphone use.

The role of the insula in internet gaming disorder.

Internet gaming disorder (IGD) is a concerning issue that requires further research. Here, we seek to examine its neural etiology with an emphasis on the role of the insula. To do so, we relied on the tripartite neurocognitive model of addictive behaviors as applied to IGD. We hypothesized that (a) video game cues will elicit stronger reward system activation and weaker prefrontal activation in gamers vs controls, (b) the IGD scores of gamers will be positively associated with activation of the reward system and negatively with activation of prefrontal regions, (c) deprivation from video gaming will result in increased activation of the insula, when gamers are exposed to video game cues vs to neutral cues, and (d) in deprivation conditions, there will be positive and negative coupling, respectively, between activation of the insula and the reward and prefrontal regions in gamers. We tested these hypotheses with a design with one between-subjects factor (gamers vs controls) and two within-subjects factors: stimuli (gaming vs neutral; for all participants) and session (deprivation vs satiety; only for gamers). Findings based on functional magnetic resonance imaging (fMRI; applied to all 52 subjects, 26 gamers, and 26 controls) and psychophysiological interaction (PPI; applied to the 26 gamers) engaged in a video reactivity task supported our assertions. The IGD score positively correlated with activity in the right ventral striatum and negatively with activity in the right dorsolateral prefrontal cortex (DLPFC). Left insular cortex activity was the highest when observing video gaming cues under deprivation. Lastly, there was an increased coupling between the left insula and left ventral striatum and a decreased coupling with left DLPFC when observing video gaming cues compared with when watching control videos in the deprivation condition.

Anxiety during abstinence from alcohol: A systematic review of rodent and human evidence for the anterior insula's role in the abstinence network.

Alcohol Use Disorder (AUD) is a chronic, relapsing disease that impacts almost a third of Americans. Despite effective treatments for attaining sobriety, the majority of patients relapse within a year, making relapse a substantial barrier to long-term treatment success. A major factor contributing to relapse is heightened negative affect that results from the combination of abstinence-related increases in stress-reactivity and decreases in reward sensitivity. Substantial research has contributed to the understanding of reward-related changes in AUD. However, less is known about anxiety during abstinence, a critical component of understanding addiction as anxiety during abstinence can trigger relapse. Most of what we know about abstinence-related negative affect comes from rodent studies which have identified key brain regions responsible for abstinence-related behaviors. This abstinence network is composed of brain regions that make up the extended amygdala: the nucleus accumbens (NAcc), the central nucleus of the amygdala (CeA), and the bed nucleus of the stria terminalis (BNST). More recently, emerging evidence from rodent and human studies suggests a fourth brain region, the anterior insula, might be part of the abstinence network. Here, we review current rodent and human literature on the extended amygdala's role in alcohol abstinence and anxiety, present evidence for the anterior insula's role in the abstinence network, and provide future directions for research to further elucidate the neural underpinnings of abstinence in humans. A better understanding of the abstinence network is critical toward understanding and possibly preventing relapse in AUD.

Remote memory of drug experiences coexists with cognitive decline and abnormal adult neurogenesis in an animal model of cocaine-altered cognition.

Cocaine addiction is a chronic disorder in which the person loses control over drug use. The past memories of the stimuli associated with the drug are a relevant clinical problem, since they trigger compulsive drug-seeking and drug-taking habits. Furthermore, these persistent drug-related memories seemingly coexist with cognitive decline that predicts worse therapeutic output. Here, we use a new animal model of cocaine-altered cognition that allowed to observe these events in the same individual and study their relationship. Mice were chronically administered cocaine in a conditioned place preference (CPP) apparatus for 14 days, and control mice received saline. After 28 days of cocaine withdrawal, animals were tested for retrieval of remote drug-associated memory as well as for cognitive performance in a battery of tests, including novel object and place recognition and spatial memory. The cocaine-withdrawn mice showed persistent CPP memory while impaired in the cognitive tasks, displaying deficits in reference memory acquisition and working memory. However, the CPP expression was not associated with the defective cognitive performance, indicating that they were concomitant but independent occurrences. After completion of the experiment, adult hippocampal neurogenesis (AHN) was studied as a relevant neurobiological correlate due to its potential role in both learning and drug addiction. Results suggested a preserved basal AHN in the cocaine-withdrawn mice but an aberrant learning-induced regulation of these neurons. This paradigm may be useful to investigate maladaptive cognition in drug addiction as well as related therapies.

Altered intrinsic connectivity distribution in internet gaming disorder and its associations with psychotherapy treatment outcomes.

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.

Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk: Towards a dimensional approach.

Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying 18 F-fallypride positron emission tomography (18 F-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.

[Parental Factors Associated with Smartphone Overuse in Preschoolers: A Systematic Review and Meta-Analysis].

PURPOSE: This study aimed to identify parental factors associated with smartphone overuse in preschoolers. METHODS: A systematic review was conducted according to PRISMA guidelines. Relevant studies published in peer-reviewed journals from 2009 to June 2019 were identified through systematic search in 10 electronic databases (PubMed, CINAHL, Cochrane Central, EMBASE, Web of Science, NDSL, KISS, KMbase, KoreaMed, and RISS). Standardized effect sizes were calculated to quantify the associations of parental factors with smartphone overuse in preschoolers using meta-analysis. RESULTS: A total of 30 cross-sectional studies involving 7,943 participants met the inclusion criteria. The following were negatively correlated with smartphone overuse in preschoolers: mother's parenting self-efficacy (r=-.35), mother-child attachment (r=-.28), mother's positive parenting behavior (r=-.28), mother's positive parenting attitude (r=-.25), and father's parenting involvement (r=-.15). Further, maternal factors such as smartphone addiction tendency (r=.41), parenting stress (r=.40), negative parenting behavior (r=.35), negative parenting attitude (r=.14), smartphone usage time (r=.26), employment status (r=.18), and age (r=.12) were positively correlated with smartphone overuse in preschoolers. CONCLUSION: Several parental factors influence smartphone overuse in preschoolers. These findings emphasize the need to assess and enhance the parental factors identified in this study to prevent smartphone overuse in preschoolers. Accordingly, we recommend the development of preventive interventions to strengthen parent-related protective factors and mitigate risk factors.

Shared gray matter alterations in individuals with diverse behavioral addictions: A voxel-wise meta-analysis.

BACKGROUND AND AIMS: Numerous studies on behavioral addictions (BAs) have reported gray matter (GM) alterations in multiple brain regions by using voxel-based morphometry (VBM). However, findings are poorly replicated and it remains elusive whether distinct addictive behaviors are underpinned by shared abnormalities. In this meta-analysis, we integrated VBM studies on different BAs to investigate common GM abnormalities in individuals with BAs. METHODS: Numerous studies on behavioral addictions (BAs) have reported gray matter (GM) alterations in multiple brain regions by using voxel-based morphometry (VBM). However, findings are poorly replicated and it remains elusive whether distinct addictive behaviors are underpinned by shared abnormalities. In this meta-analysis, we integrated VBM studies on different BAs to investigate common GM abnormalities in individuals with BAs. RESULTS: Twenty studies including 505 individuals with BAs and 564 healthy controls met the inclusion criteria. Compared with healthy controls, individuals with BAs showed GM atrophy in the left anterior cingulate (extending to the left medial superior frontal gyrus and bilateral orbitofrontal gyrus), right putamen and right supplementary motor area. Subgroup analysis found heterogeneity in gender and subtypes of BAs. Meta-regression revealed that GM decreases in the left anterior cingulate and right supplementary motor area were positively correlated with addictive severity. Higher impulsivity was associated with smaller volume of the left anterior cingulate. DISCUSSION AND CONCLUSIONS: Our findings on BAs were mainly derived from internet gaming disorder (IGD) and pathological gambling (PG) studies, preliminarily suggesting that GM atrophy in the prefrontal and striatal areas might be a common structural biomarker of BAs.

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological evidence demonstrating that cannabinoids can also alter the brain's initial molecular and epigenetic response to cocaine. Here, we utilized a multiomics approach (epigenomics, transcriptomics, proteomics, and phosphoproteomics) to characterize how the rat brain responds to its first encounter with cocaine, with or without preexposure to the synthetic cannabinoid WIN 55,212-2 (WIN). We find that in adolescent (but not in adult) rats, preexposure to WIN results in cross-sensitization to cocaine, which correlates with histone hyperacetylation and decreased levels of HDAC6 in the prefrontal cortex (PFC). In the PFC, we also find that WIN preexposure blunts the typical mRNA response to cocaine and instead results in alternative splicing and chromatin accessibility events, involving genes such as Npas2 Moreover, preexposure to WIN enhances the effects of cocaine on protein phosphorylation, including ERK/MAPK-targets like gephyrin, and modulates the synaptic AMPAR/GluR composition both in the PFC and the nucleus accumbens (NAcc). PFC-NAcc gene network topological analyses, following cocaine exposure, reveal distinct top nodes in the WIN preexposed group, which include PACAP/ADCYAP1. These preclinical data demonstrate that adolescent cannabinoid exposure reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

Lateral orbitofrontal gray matter abnormalities in subjects with problematic smartphone use.

BACKGROUND AND AIMS: Smartphone use is becoming commonplace and exerting adequate control over smartphone use has become an important mental health issue. Little is known about the neurobiology underlying problematic smartphone use. We hypothesized that structural abnormalities in the fronto-cingulate brain region could be implicated in problematic smartphone use, similar to that has been reported for Internet gaming disorder and Internet addiction. This study investigated fronto-cingulate gray matter abnormalities in problematic smartphone users, particularly those who spend time on social networking platforms. METHODS: The study included 39 problematic smartphone users with excessive use of social networking platforms via smartphone and 49 normal control male and female smartphone users. We conducted voxel-based morphometric analysis with diffeomorphic anatomical registration using an exponentiated Lie algebra algorithm. Region of interest analysis was performed on the fronto-cingulate region to identify whether gray matter volume (GMV) differed between the two groups. RESULTS: Problematic smartphone users had significantly smaller GMV in the right lateral orbitofrontal cortex (OFC) than healthy controls, and there were significant negative correlations between GMV in the right lateral OFC and the Smartphone Addiction Proneness Scale (SAPS) score, including the SAPS tolerance subscale. CONCLUSIONS: These results suggest that lateral orbitofrontal gray matter abnormalities are implicated in problematic smartphone use, especially in social networking platform overuse. Small GMV in the lateral OFC was correlated with an increasing tendency to be immersed in smartphone use. Our results suggest that orbitofrontal gray matter abnormalities affect regulatory control over previously reinforced behaviors and may underlie problematic smartphone use.

Microstructural changes and internet addiction behaviour: A preliminary diffusion MRI study.

Internet addiction (IA) is a major health problem and is associated with comorbidities like insomnia and depression. These consequences frequently confound neuroanatomical correlates of IA in those suffering from it. We enrolled a number of 123 healthy native German-speaking adults (53 male, mean age: 36.8 ±â€¯18.86) from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) database, for whom diffusion MRI data, internet addiction test, brief self-control scale (SCS), coping orientations to problems experienced (COPE), and depression scores were available. DMRI connectometry was used to investigate white matter microstructural correlates of the severity of internet addiction identified through IAT, in a group of healty young individuals. A multiple regression model was adopted with age, gender, SCS total score, COPE total score, and BDI-sum as covariates to track white matter fibers in which connectivity was associated with IAT. The connectometry analysis identified a direct correlation between connectivity in the splenium of corpus callosum (CC), parts of bilateral corticospinal tracts (CST), and bilateral arcuate fasciculi (AF) (FDR = 0.0023001), and an inverse correlation of the connectivity in the genu of CC and right fornix (FDR = 0.047138), with the IAT score in healthy adults. We suggest connectivity in the CC and CST as well as fornix and AF to be considered as microstructural biomarkers of predisposition to IA in healthy population.

A Comparison of Risk and Protective Factors for Excessive Internet Game Play between Koreans in Korea and Immigrant Koreans in the United States.

BACKGROUND: Studying immigrants may have the potential to explore how cultural and environmental changes affect the internet game play patterns of individuals in the two countries. We planned to compare risk and preventive factors for Internet Gaming Disorder (IGD) between Korean adolescents in Korea and immigrant Koreans in the US. METHODS: Ninety-four Koreans and 133 immigrant Koreans were recruited. Independent factors consisted of five domains including demographic data, physical activity, academic, art, and music activities, psychological factors, and game and media play. The dependent variable in the current study was the high-risk group of IGD, which was assessed with Young's Internet Addiction Scale scores. To determine the protective and risk factors for IGD, we performed a multiple logistic regression analysis using the high-risk group as the dependent variable. RESULTS: Five domains affected the risk for IGD in Korean and immigrant Korean groups. Vigorous physical activity was the strongest protective factor for IGD in the Korean group, while media activity was the strongest protective factor for IGD in immigrant Koreans in the US. CONCLUSION: The results indicate that internet gaming problems might be affected by environmental factors and it is recommended that gaming activity is substituted with physical activity, extracurricular classes, books, and music.

Function and Mechanism of Myelin Regulation in Alcohol Abuse and Alcoholism.

Excessive alcohol use has adverse effects on the central nervous system (CNS) and can lead to alcohol use disorders (AUDs). Recent studies have suggested that myelin reductions may directly contribute to CNS dysfunctions associated with AUDs. Myelin consists of compact lipid membranes wrapped around axons to provide electrical insulation and trophic support. Regulation of myelin is considered as a new form of neural plasticity due to its profound impacts on the computation of neural networks. In this review, the authors first discuss experimental evidence showing how alcohol exposure causes demyelination in different brain regions, often accompanied by deficits in cognition and emotion. Next, they discuss postulated molecular and cellular mechanisms underlying alcohol's impact on myelin. It is clear that more extensive investigations are needed in this important but underexplored research field in order to gain a better understanding of the myelin-behavior relationship and to develop new treatment strategies for AUDs.

The concept of exposure when selecting comparison groups for determining individual susceptibility to addiction to cigarette smoking.

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.