Understanding e-Cigarette Addictiveness: Triangulation of Focus Group and Netnographic Data.

BACKGROUND: Numerous studies have shown that e-cigarettes are addictive. For example, we previously showed that users of e-cigarette online forums discuss experiences of addiction in a netnographic analysis. However, it is unclear what makes e-cigarettes addictive apart from nicotine. In a focus group analysis, we recently identified 3 unique features of e-cigarettes that users linked to experiences of addiction: the pleasant taste, unobtrusiveness, and unlimited usability of e-cigarettes. OBJECTIVE: This study aimed to validate the previously identified features of e-cigarette addictive potential by triangulating data from the netnographic analysis and focus group discussions. METHODS: Drawing on a netnographic analysis of 3 popular, German-language e-cigarette forums, we studied whether experiences of addiction were linked to specific e-cigarette features. We included 451 threads in the analysis that had been coded for addictive experiences in a previous study by our team. First, we conducted a deductive analysis with preregistered codes to determine whether the features of pleasant taste, unobtrusiveness, and unlimited usability were mentioned in relation to the addictive potential of e-cigarettes in the online forums. Second, an inductive approach was chosen to identify further possible addictive features of e-cigarettes. RESULTS: Our deductive analysis confirmed that the features highlighted in our previous focus group study (pleasant taste, unobtrusiveness, and unlimited usability) were also frequently discussed in online forums in connection to addictive symptoms. In addition, our inductive analysis identified nicotine dosage as a significant feature linked to addiction. Users reported varying their nicotine doses for different reasons, leading to the identification of four distinct user types based on dosing patterns: (1) high doses for intermittent, (2) high doses for constant use, (3) low doses for constant use, and (4) switching between high and low doses depending on the situation. CONCLUSIONS: Our comprehensive analysis of online forum threads revealed that users' experiences of addiction are linked to 4 specific features unique to e-cigarettes: pleasant taste, unobtrusiveness, unlimited usability, and nicotine dosage. Recognizing these addictive features of e-cigarettes is crucial for designing cessation programs and informing public health policies to reduce the addictiveness of e-cigarettes.

The association between adverse childhood experiences and alterations in brain volume and cortical thickness in adults with alcohol use disorder.

BACKGROUND: Previous studies have established a connection between adverse childhood experiences (ACE) and alcohol use disorder (AUD), both of which are associated with alterations in grey matter volume (GMV) and cortical thickness (CT). The current study aimed to assess the neurobiological impact of ACE specifically in the context of AUD, as well as the role of maltreatment type (i.e., abuse or neglect) and timing. METHODS: Structural MRI data were collected from 35 adults with AUD (mean age: 40; 31% female) and 28 healthy controls (mean age: 36; 61% female). ACE were assessed retrospectively using the Childhood Trauma Questionnaire, and the Maltreatment and Abuse Chronology interview. Global and regional GMV and CT were estimated using voxel- and surface-based morphometry. RESULTS: Relative to the healthy controls, the AUD group had significantly reduced CT in the left inferior frontal gyrus, left circular sulcus of the insula and subcentral gyrus and sulci (cluster C1), and in the central sulcus and precentral gyrus (cluster C2). Within the AUD group, a reduction of CT in cluster C1 was significantly associated with higher severity of ACE and AUD. Type and timing analyses revealed a significant association between higher levels of abuse at ages 13 to 15 and reduced CT in cluster C1 within the AUD group. CONCLUSIONS: In adults with AUD, abuse experienced during early adolescence is associated with reduced CT in regions involved in inhibitory control, indicating the potential relevance of cognitive pathways in the association between ACE and AUD. Longitudinal studies are needed to confirm and expand upon current findings.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

The Role of Perceived Stress in the Relation between Childhood Maltreatment and Severity of Alcohol Use Disorder: A Mediation Analysis.

INTRODUCTION: Experiences of Childhood Maltreatment (CM) relate to relapse and lower treatment success in Alcohol Use Disorder (AUD), one of the most prevalent substance use disorders. However, the exact mechanisms of this relationship still remain unclear. This study examines perceived stress and "drinking to cope with negative affect" (coping) as possible mediators in this relationship. Moreover, it aims at uncovering the differential effects of the subtypes of CM. METHODS: N = 96 individuals (42% women; mean age 41 ± 13 years) including healthy controls and individuals with varying severity of AUD and CM completed the Alcohol-Dependence Scale, Childhood Trauma Questionnaire, Perceived Stress Scale and German Inventory of Drinking Situations. Mediation analyses including perceived stress as a mediator between CM (and subtypes) and severity of AUD, as well as a serial mediation of the relationship between CM and AUD severity by perceived stress and coping were conducted. RESULTS: Perceived stress significantly mediated the relation between CM and AUD severity and the serial mediation by perceived stress and coping turned out significant. Subtype-specific analyses did not yield significant results. CONCLUSION: This study reinforces perceived stress as a potential mechanism in the relation between CM and AUD severity. Moreover, coping further mediated the relationship between CM and AUD severity. Our results suggest including screening for CM (subtypes) in clinical routine in order to individually emphasize interventions focusing on stress regulation, as well as on developing healthy coping mechanisms, in patients with AUD. This might prevent heightened stress sensitivity, relapse and further maintenance of AUD.

Sports participation moderates the risk of family-specific negative life events on alcohol use among adolescents: Evidence from the longitudinal MyLife study.

Negative life events (NLE) have been associated with increased alcohol use (AU) during adolescence. However, whether this risk association may be modified by leisure activities such as sports participation (SP) remains poorly understood. This study examined whether accumulated family-specific NLE in particular were associated with greater AU, and if so, whether SP moderated this association to reduce AU among high-NLE adolescents. We examined five annual assessments from a nationwide cohort of 3,422 Norwegian adolescents (13-15 year-olds; 55.3 % girls at baseline) who participated in the MyLife study. At each assessment, adolescents reported their AU on the Alcohol Use Disorders Identification Test-Concise (AUDIT-C), the number of family-specific NLE in the past 12 months, SP days in the past 30 days, and multiple sociodemographic and individual-level characteristics (covariates). Changes over time in AU as a function of NLE, SP, and their interaction (NLExSP) were examined with a set of partially nested growth curve models. AU increased non-linearly over time in all models. The fully adjusted best-fitting model showed significant NLExSP interactions (estimate = -0.013, 95% CI [-0.02, -0.006]), such that the initial AUDIT-C scores were lower for high-NLE adolescents with high SP and greater for high-NLE adolescents with low SP. Further, linear increases in AU over time were marginally steeper for high-NLE adolescents with high SP (NLExSPxTime estimate = 0.034, 95% CI [-0.0002, 0.007]). Thus, SP appeared to have a protective role in reducing AU for high-NLE youth primarily during middle school years. Prevention efforts thus may utilize organized sports for youth facing family-specific NLE as a resource early on.

Cue-exposure treatment influences resting-state functional connectivity-a randomized controlled fMRI study in alcohol use disorder.

RATIONALE: Cue-exposure therapy (CET) consists of exposing patients to the cause of their affliction in a controlled environment and after psychological preparation. Ever since it was conceived, it has been suggested as a treatment for different types of behavioural impairments, from anxiety disorders to substance abuse. In the field of addictive behaviour, many different findings have been shown regarding the effectiveness of this therapy. OBJECTIVES: This study aims to examine the underlying neurobiological mechanisms of the effects of CET in patients with alcohol use disorder using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: In a randomized, controlled study, we examined patients after inpatient detoxification as well as healthy controls. Patients underwent nine sessions of CET spaced over 3 weeks. Rs-fMRI was conducted before treatment and 3 weeks after treatment onset in patients, healthy controls received only one rs-fMRI measurement. The final participant sample with complete data included 35 patients in the CET group, 17 patients in the treatment-as-usual group, and 43 HCs. RESULTS: Our results show differences in the Salience Network when comparing the CET group to the treatment-as-usual group (TAU). Functional connectivity between the anterior cingulate Cortex (ACC) and the insula was increased after CET, whereas it was decreased from ACC to the putamen and globus pallidus. Further, increased connectivity with the precuneus was found in the dorsal attention network after cue exposure treatment. CONCLUSIONS: These findings suggest that cue exposure therapy changes the resting-state brain connectivity with additional effects to the standard psychotherapy treatment. Hence, our study results suggest why including CET in standard therapies might improve the preparation of patients in front of daily situations.

Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder.

BACKGROUND: Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. METHODS: Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. RESULTS: Compared with both control conditions, psychosocial stress elicited higher alcohol cue-induced activation in the left anterior insula (familywise error-corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate-corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate-corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate-corrected p = .046). CONCLUSIONS: Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

Effectiveness of Reducing Craving in Alcohol Use Disorder Using a Serious Game (SALIENCE): Randomized Controlled Trial.

BACKGROUND: Alcohol use disorder (AUD) has become a major global health problem. Therapy for this condition is still a great challenge. Recently, it has become increasingly evident that computer-based training is a valuable addition to the treatment of addictive disorders. OBJECTIVE: This study aims to evaluate the web-based serious game SALIENCE (Stop Alcohol in Everyday Life-New Choices and Evaluations) as an add-on therapy for AUD. It combines the cue-exposure therapy approach with elements of decision-making training, enhanced by interactive panoramic images. The effects of SALIENCE training on levels of craving, attention, and cognitive bias are investigated. METHODS: In a randomized controlled trial, 62 participants with AUD undergoing 3 weeks of an extended alcohol detoxification program were randomly allocated to an intervention and a control group. A total of 49 individuals (mean age 44.04 y; 17/49, 35% female) completed all sessions and were included in the analysis. Only pretreatment data were available from the other 13 patients. Participants answered questionnaires related to alcohol consumption and craving and completed neuropsychological tasks at the beginning of the study and 2 weeks later to evaluate levels of attention and cognitive biases. During the 2-week period, 27 of the participants additionally performed the SALIENCE training for 30 minutes 3 times a week, for a total of 6 sessions. RESULTS: We observed a significant decrease in craving in both groups: the control group (mean 15.59, SD 8.02 on the first examination day vs mean 13.18, SD 8.38 on the second examination day) and the intervention group (mean 15.19, SD 6.71 on the first examination day vs mean 13.30, SD 8.47 on the second examination day; F1,47=4.31; P=.04), whereas the interaction effect was not statistically significant (F1,47=0.06; P=.80). Results of the multiple linear regression controlling for individual differences between participants indicated a significantly greater decrease in craving (ß=4.12; t36=2.34; P=.03) with the SALIENCE intervention. Participants with lower drinking in negative situations reduced their craving (ß=.38; t36=3.01; P=.005) more than people with higher drinking in negative situations. CONCLUSIONS: The general effectiveness of SALIENCE training as an add-on therapy in reducing alcohol craving was not confirmed. Nevertheless, taking into account individual differences (gender, duration of dependence, stress, anxiety, and drinking behavior in different situations), it was shown that SALIENCE training resulted in a larger reduction in craving than without. Notably, individuals who rarely consume alcohol due to negative affect profited the most from SALIENCE training. In addition to the beneficial effect of SALIENCE training, these findings highlight the relevance of individualized therapy for AUD, adapted to personal circumstances such as drinking motivation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03765476; https://clinicaltrials.gov/show/NCT03765476.

The Role of Unawareness, Volition, and Neural Hyperconnectivity in Alcohol Use Disorder: A Functional Magnetic Resonance Imaging Study.

BACKGROUND: Automated alcohol craving and habitual alcohol consumption characterize the later stages of alcohol use disorder (AUD). This study reanalyzed previously collected functional neuroimaging data in combination with the Craving Automated Scale for Alcohol (CAS-A) questionnaire to investigate the neural correlates and brain networks underlying automated drinking characterized by unawareness and nonvolition. METHODS: We assessed 49 abstinent male patients with AUD and 36 male healthy control participants during a functional magnetic resonance imaging-based alcohol cue-reactivity task. We performed whole-brain analyses examining the associations between CAS-A scores and other clinical instruments and neural activation patterns in the alcohol versus neutral contrast. Furthermore, we performed psychophysiological interaction analyses to assess the functional connectivity between predefined seed regions and other brain areas. RESULTS: In patients with AUD, higher CAS-A scores correlated with greater activation in dorsal striatal, pallidal, and prefrontal regions, including frontal white matter, and with lower activation in visual and motor processing regions. Between-group psychophysiological interaction analyses showed extensive connectivity between the seed regions inferior frontal gyrus and angular gyrus and several frontal, parietal, and temporal brain regions in AUD versus healthy control participants. CONCLUSIONS: The present study applied a new lens to previously acquired alcohol cue-reactivity functional magnetic resonance imaging data by correlating neural activation patterns with clinical CAS-A scores to elucidate potential neural correlates of automated alcohol craving and habitual alcohol consumption. Our results support previous findings showing that alcohol addiction is associated with hyperactivation in habit-processing regions, with hypoactivation in areas mediating motor and attention processing, and with general hyperconnectivity.

Drinking alcohol to cope with hyperactive ADHD? Self-reports vs. continuous performance test in patients with ADHD and/or alcohol use disorder.

Rationale: Attention deficit/hyperactivity disorder (ADHD) is common in alcohol use disorder (AUD). Continuous performance tests (CPTs) allow to measure ADHD related deficits in a laboratory setting. Most studies on this topic focused on CPTs measuring inattention or impulsivity, disregarding hyperactivity as one of the core symptoms of ADHD. Methods: We examined N = 47 in three groups (ADHD N = 19; AUD N = 16; ADHD + AUD N = 12) with questionnaires on ADHD core symptoms, executive functioning (EF), mind wandering, and quality of life (QoL). N = 46 (ADHD N = 16; AUD N = 16; ADHD + AUD N = 14) were examined with a CPT (QbTest®) that also measures motor activity objectively. Results: Inattention and impulsivity were significantly increased in AUD vs. ADHD and in AUD vs. ADHD + AUD. Hyperactivity was significantly higher in ADHD + AUD vs. ADHD and ADHD + AUD vs. AUD, but not in ADHD vs. AUD. EF was lower in both ADHD groups vs. AUD. Mind wandering was increased in both ADHD groups vs. AUD. QoL was significantly lower in ADHD + AUD compared to AUD. In contrast, results of the QbTest were not significantly different between groups. Conclusion: Questionnaires are more useful in assessing ADHD core symptoms than the QbTest®. Hyperactivity appears to be a relevant symptom in ADHD + AUD, suggesting a possible pathway from ADHD to AUD. The lower QoL in ADHD + AUD emphasizes the need for routine screening, diagnostic procedures and treatment strategies for this patient group.

Decoding fMRI alcohol cue reactivity and its association with drinking behaviour.

BACKGROUND: Cue reactivity, the enhanced sensitivity to conditioned cues, is associated with habitual and compulsive alcohol consumption. However, most previous studies in alcohol use disorder (AUD) compared brain activity between alcohol and neutral conditions, solely as cue-triggered neural reactivity. OBJECTIVE: This study aims to find the neural subprocesses during the processing of visual alcohol cues in AUD individuals, and how these neural patterns are predictive for relapse. METHODS: Using cue reactivity and rating tasks, we separately modelled the patterns decoding the processes of visual object recognition and reward appraisal of alcohol cues with representational similarity analysis, and compared the decoding involvements (ie, distance between neural responses and hypothesised decoding models) between AUD and healthy individuals. We further explored connectivity between the identified neural systems and the whole brain and predicted relapse within 6 months using decoding involvements of the neural patterns. FINDINGS: AUD individuals, compared with healthy individuals, showed higher involvement of motor-related brain regions in decoding visual features, and their reward, habit and executive networks were more engaged in appraising reward values. Connectivity analyses showed the involved neural systems were widely connected with higher cognitive networks during alcohol cue processing in AUD individuals, and decoding involvements of frontal eye fields and dorsolateral prefrontal cortex could contribute to relapse prediction. CONCLUSIONS: These findings provide insight into how AUD individuals differently decode alcohol cues compared with healthy participants, from the componential processes of visual object recognition and reward appraisal. CLINICAL IMPLICATIONS: The identified patterns are suggested as biomarkers and potential therapeutic targets in AUD.

Understanding perceived addiction to and addictiveness of electronic cigarettes among electronic cigarette users: a cross-sectional analysis of the International Tobacco Control Smoking and Vaping (ITC 4CV) England Survey.

BACKGROUND AND AIMS: The addictive potential of electronic cigarettes (e-cigarettes) remains to be fully understood. We identified patterns and correlates of perceived addiction to e-cigarettes and perceived addictiveness of e-cigarettes relative to tobacco cigarettes (relative addictiveness) in dual users as well as exclusive e-cigarette users. DESIGN, SETTING AND PARTICIPANTS: Observational study using cross-sectional survey data from England (2016) from the International Tobacco Control Project (ITC) Four Country Smoking and Vaping (4CV) survey. The study comprised 832 current e-cigarette users who had been vaping for at least 4 months. MEASUREMENTS: Perceived addiction to e-cigarettes and relative addictiveness of e-cigarettes were examined. Socio-demographic factors were age, gender and education; markers of addiction included urge to vape, time to first vape after waking and nicotine strength used; vaping and smoking characteristics included frequency and duration of e-cigarette use, intention to quit, adjustable power or temperature, enjoyment, satisfaction relative to tobacco cigarettes and tobacco cigarette smoking status. FINDINGS: A total of 17% of participants reported feeling very addicted to e-cigarettes, while 40% considered e-cigarettes equally/more addictive than tobacco cigarettes. Those who felt very addicted had higher odds of regarding e-cigarettes as more addictive than tobacco cigarettes (odds ratio 3.4, 95% confidence interval 2.3-5.1). All markers of addiction, daily use and enjoyment were associated with higher perceived addiction, whereas time to first vape after waking, daily vaping and perceiving vaping as less satisfying than smoking were associated with relative addictiveness. CONCLUSIONS: Markers of addiction to e-cigarettes appear to correspond with perceived addiction to e-cigarettes, suggesting that self-reported perceived addiction might serve as an indicator of addiction. Prevalence both of markers of addiction and perceived addiction were comparatively low overall, suggesting a limited but relevant addictive potential of e-cigarettes. Additionally, positive and negative reinforcement, reflected here by enjoyment and relative satisfaction, might play a role in e-cigarette addiction.

MRI texture-based radiomics analysis for the identification of altered functional networks in alcoholic patients and animal models.

Alcohol use disorder (AUD) is a complex condition representing a leading risk factor for death, disease and disability. Its high prevalence and severe health consequences make necessary a better understanding of the brain network alterations to improve diagnosis and treatment. The purpose of this study was to evaluate the potential of resting-state fMRI 3D texture features as a novel source of biomarkers to identify AUD brain network alterations following a radiomics approach. A longitudinal study was conducted in Marchigian Sardinian alcohol-preferring msP rats (N = 36) who underwent resting-state functional and structural MRI before and after 30 days of alcohol or water consumption. A cross-sectional human study was also conducted among 33 healthy controls and 35 AUD patients. The preprocessed functional data corresponding to control and alcohol conditions were used to perform a probabilistic independent component analysis, identifying seven independent components as resting-state networks. Forty-three radiomic features extracted from each network were compared using a Wilcoxon signed-rank test with Holm correction to identify the network most affected by alcohol consumption. Features extracted from this network were then used in the machine learning process, evaluating two feature selection methods and six predictive models within a nested cross-validation structure. The classification was evaluated by computing the area under the ROC curve. Images were quantized using different numbers of gray-levels to test their influence on the results. The influence of ageing, data preprocessing, and brain iron accumulation were also analyzed. The methodology was validated using structural scans. The striatal network in alcohol-exposed msP rats presented the most significant number of altered features. The radiomics approach supported this result achieving good classification performance in animals (AUC = 0.915 ± 0.100, with 12 features) and humans (AUC = 0.724 ± 0.117, with 9 features) using a random forest model. Using the structural scans, high accuracy was achieved with a multilayer perceptron in both species (animals: AUC > 0.95 with 2 features, humans: AUC > 0.82 with 18 features). The best results were obtained using a feature selection method based on the p-value. The proposed radiomics approach is able to identify AUD patients and alcohol-exposed rats with good accuracy, employing a subset of 3D features extracted from fMRI. Furthermore, it can help identify relevant networks in drug addiction.

Using computer-based habit versus chess-based cognitive remediation training as add-on therapy to modify the imbalance between habitual behavior and cognitive control in tobacco use disorder: protocol of a randomized controlled, fMRI study.

BACKGROUND: Although the vast majority of smokers are aware of the enormous preventable health hazards caused by smoking, only a small percentage of smokers manage to remain abstinent in the long term. One possible explanation for this discrepancy lies in the inflexibility of addictive behavior and associated disadvantageous decision-making. According to a dual-process theory of decision-making, two distinct decision systems can be identified. One slow deliberate system based on desirable expectations of outcome value described as goal-directed behavior and a fast reflexive system based on habitual instrumental behavior and driven by reinforcement experienced in the past. In the course of addiction development, an imbalance occurs between habitual behavior and goal-directed. The present study aims to investigate the modifiability of the balance between habitual and goal-directed behavior at the neurobiological and behavioral level in smokers using two different novel add-on therapies. We hypothesize that both interventions change the balance between goal-directed and habitual behavior, but by different mechanisms. Whereas a cognitive remediation treatment should directly improve cognitive control, in contrast an implicit priming task should affect the early processing and the emotional valence of smoking and smoking cues. METHODS: We will conduct a randomized controlled study in treatment-seeking individuals with tobacco use disorder applying either chess-based cognitive remediation training (N = 30) or implicit computer-based habit-modifying training (N = 30) as add on therapy compared to the standard smoking cessation group therapy (N = 30) only. We will address neurobiological and neuropsychological correlates associated with craving, reward devaluation, cue reactivity and attentional bias. In addition, various effects of treatment and prediction of treatment outcome will be examined using behavioral and neural measures. DISCUSSION: The present study will apply different examination methods such as functional magnetic resonance imaging, neuropsychological tests, and self-report before and after the interventions. This allows the identification of intervention-specific mechanisms and therefore potential neurobiology-based specific treatment targets for individuals with Tobacco Use Disorder. TRIAL REGISTRATION: Registered at clinicaltrials.gov/ct2/show/NCT03764969 (05 December 2018).

Addictive Potential of e-Cigarettes as Reported in e-Cigarette Online Forums: Netnographic Analysis of Subjective Experiences.

BACKGROUND: While e-cigarettes usually contain nicotine, their addictive potential is not yet fully understood. We hypothesized that if e-cigarettes are addictive, users will experience typical symptoms of addiction. OBJECTIVE: The aim of our study was to investigate whether and how e-cigarette users report signs of addiction. METHODS: We identified 3 large German-language e-cigarette online forums via a systematic Google search. Based on a netnographic approach, we used deductive content analysis to investigate relevant posts in these forums. Netnography has the advantage of limiting the social desirability bias that prevails in face-to-face research, such as focus groups. The data were coded according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for tobacco use disorder, adapted for e-cigarettes. The DSM-5 criteria were used to portray a broad spectrum of possible experiences of addiction. RESULTS: Overall, 5337 threads in 3 forums were screened, and 451 threads containing relevant information were included in the analysis. Users reported experiences consistent with the DSM-5 criteria, such as craving e-cigarettes, excessive time spent vaping, and health issues related to e-cigarette use. However, our analysis also showed that users reported the absence of typical tobacco use disorder criteria, such as successful attempts to reduce the nicotine dosage. For most themes, reports of their absence were more frequent than of their presence. The absence of perceived addiction was mostly reported in contrast to prior tobacco smoking. CONCLUSIONS: This is the first study to use a netnographic approach to explore unfiltered self-reports of experiences of e-cigarette addiction by users in online forums. As hypothesized, some but not all users reported subjective experiences that corresponded to the criteria of tobacco use disorder as defined by the DSM-5. Nevertheless, subjective reports also indicated that many e-cigarette users felt in control of their behavior, especially in contrast to their prior use of tobacco cigarettes. The finding that some e-cigarette users subjectively experience addiction highlights the need for effective cessation programs to support users who experience their e-cigarette use as burdensome. This research can guide the refinement of instruments to assess e-cigarette addiction and guide cessation programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s40359-021-00682-8.

Lack of amygdala habituation to negative emotional faces in alcohol use disorder and the relation to adverse childhood experiences.

Aberrant limbic circuit reactivity to negative stimuli might be related to alterations in emotion processing and regulation in alcohol use disorder (AUD). The current study tested for the first time in AUD the hypothesis of aberrant amygdala habituation to repeated aversive stimuli-a robust and reliable neuroimaging marker for emotion processing. We explored the link between deficits in habituation to adverse childhood experience (ACE), a common risk factor for impaired emotion regulation and AUD. AUD individuals (N = 36) and healthy controls (HC; N = 26) participated in an observational case-control functional magnetic resonance imaging (fMRI) study. An established habituation index was used to investigate processing of aversive emotional faces of the amygdala. AUD individuals showed an overall deficit in amygdala habituation (right: t = 4.26, pFWE = 0.004; left: t = 4.79, pFWE ≤ 0.001). Amygdala habituation was significantly related to increased exposure to ACE in HC (t = 3.88, pFWE = 0.012), whereas this association was not observed in AUD individuals (T = 1.80, pFWE = 0.662). Further, a significant association between higher alcohol consumption and reduced amygdala habituation (right: R2  = -0.356, F = 8.736, p = 0.004; left: R2  = -0.309, F = 6.332, p = 0.015) was observed. We found novel evidence for neural alterations in emotion processing in AUD individuals, indexed by deficient amygdala habituation to negative emotional content. We replicated a prior report on a link between ACE and amygdala habituation, a well-established environmental risk factor for mental disorders and emotion dysregulation, in our control sample. Additionally, deficient amygdala habituation related to the amount of alcohol consumption in the overall sample might indicate a short-term substance effect.

Association between iron accumulation in the dorsal striatum and compulsive drinking in alcohol use disorder.

RATIONALE: Brain iron accumulation has been observed in neuropsychiatric disorders and shown to be related to neurodegeneration. OBJECTIVES: In this study, we used quantitative susceptibility mapping (QSM), an emerging MRI technique developed for quantifying tissue magnetic susceptibility, to examine brain iron accumulation in individuals with alcohol use disorder (AUD) and its relation to compulsive drinking. METHODS: Based on our previous projects, QSM was performed as a secondary analysis with gradient echo sequence images, in 186 individuals with AUD and 274 healthy participants. Whole-brain susceptibility values were calculated with morphology-enabled dipole inversion and referenced to the cerebrospinal fluid. Then, the susceptibility maps were compared between AUD individuals and healthy participants. The relationship between drinking patterns and susceptibility was explored. RESULTS: Whole-brain analyses showed that the susceptibility in the dorsal striatum (putamen and caudate) among AUD individuals was higher than healthy participants and was positively related to the Obsessive Compulsive Drinking Scale (OCDS) scores and the amount of drinking in the past three months. CONCLUSIONS: Increased susceptibility suggests higher iron accumulation in the dorsal striatum in AUD. This surrogate for the brain iron level was linearly associated with the compulsive drinking pattern and the recent amount of drinking, which provides us a new clinical perspective in relation to brain iron accumulation, and also might indicate an association of AUD with neuroinflammation as a consequence of brain iron accumulation. The iron accumulation in the striatum is further relevant for functional imaging studies in AUD by potentially producing signal dropout and artefacts in fMRI images.

Reward Processing in Alcohol-Dependent Patients and First-Degree Relatives: Functional Brain Activity During Anticipation of Monetary Gains and Losses.

BACKGROUND: According to the reward deficiency syndrome and allostatic hypotheses, hyposensitivity of mesocorticolimbic regions to non-alcohol-related stimuli predisposes to dependence or is long-lastingly enhanced by chronic substance use. To date, no study has directly compared mesocorticolimbic brain activity during non-drug reward anticipation between alcohol-dependent, at risk, and healthy subjects. METHODS: Seventy-five abstinent alcohol-dependent human subjects (mean abstinence duration 957.66 days), 62 healthy first-degree relatives of alcohol-dependent individuals, and 76 healthy control subjects without family history of alcohol dependence performed a monetary incentive delay task. Functional magnetic resonance imaging data of the anticipation phase were analyzed, during which visual cues predicted that fast response to a target would result in monetary gain, avoidance of monetary loss, or a neutral outcome. RESULTS: During gain anticipation, there were no significant group differences. During loss anticipation, abstinent alcohol-dependent subjects showed lower activity in the left anterior insula compared with healthy control subjects without family history of alcohol dependence only (Montreal Neurological Institute [MNI] -25 19 -5; t206 = 4.17, familywise error corrected p = .009). However, this effect was no longer significant when age was included as a covariate. There were no group differences between abstinent alcohol-dependent subjects and healthy first-degree relatives or between healthy first-degree relatives and healthy control subjects during loss anticipation, respectively. CONCLUSIONS: Neither the neural reward deficiency syndrome nor the allostatic hypotheses are supported by the results. Future studies should investigate whether the incentive salience hypothesis allows for more accurate predictions regarding mesocorticolimbic brain activity of subjects with alcohol dependence and healthy individuals during reward and loss anticipation and further examine the neural substrates underlying a predisposition to dependence.

Neural cue reactivity is not stronger in male than in female patients with alcohol use disorder.

Background: Males consume more alcohol than females, and alcohol use disorder (AUD) is more prevalent in males than females. However, females progress faster to AUD. Sex differences in neural alcohol cue reactivity were previously observed in young social drinkers, indicating a role of hypersensitivity to alcohol-related cues in very early stages of addiction. To our knowledge, this is the first study on patients diagnosed with AUD to test sex differences in neural reactivity to alcohol cues in order to widen previous findings. Methods: We analyzed data from previous studies, using a well-established functional magnetic resonance imaging (fMRI) paradigm to compare neural reactivity to alcohol cues between 42 female and 124 male patients with AUD (mean age 45 and 46 years) in predefined regions of interest that were implicated by previous studies (ventral and dorsal striatum as well as caudate, putamen, amygdala, hippocampus, insula, anterior cingulate cortex, and medial prefrontal cortex) using independent samples t-tests. Post-hoc, effect size calculations were performed. Results: Throughout all nine regions of interest, we found no statistically significant sex differences in neural reactivity toward alcoholic pictures alone or in comparison to neutral pictures (p > 0.05, FDR-corrected). Post-hoc effect size estimates indicated a magnitude between 0.137 and 0.418 (Hedge's g) on alcohol reactivity to alcohol cues compared to neutral cues and indicate very small to less than medium effect sizes in the direction of higher cue reactivity in female patients. Conclusion: Previous studies showed sex differences in neural alcohol cue reactivity in younger social and problematic alcohol drinkers, i.e., stronger striatal cue-reactivity in males. After correction for multiple comparisons, we did not observe significant sex differences in a cohort of middle-aged females and males with AUD. Sex differences that are present during early phases of addiction development might disappear at later stages of AUD and might thus be considered as clinically less relevant in patients with more severe AUD.