Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Student-, Study- and COVID-19-Related Predictors of Students' Smoking, Binge Drinking and Cannabis Use before and during the Initial COVID-19 Lockdown in The Netherlands.

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.

Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use.

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.

White matter microstructure differences in individuals with dependence on cocaine, methamphetamine, and nicotine: Findings from the ENIGMA-Addiction working group.

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.

Investigating the association between smoking, environmental tobacco smoke exposure and reward-related brain activity in adolescent experimental smokers.

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.

Mechanisms of change in a go/no-go training game for young adult smokers.

Objective: Smoking is a major cause of worldwide morbidity and mortality. Evidence-based intervention programs to help young adults quit smoking are largely lacking; identifying targets for intervention is therefore critical. A candidate target is inhibitory control, with previous studies on Go/No-Go trainings showing behavior change in the food and alcohol domain. The current study examined the mechanisms of change of HitnRun, a Go/No-Go game, in a smoking population that was motivated to quit. Method: A 2-armed experimental study (n = 106) was conducted and young adults (Mage = 22.15; SDage = 2.59) were randomly assigned to either play HitnRun or to read a psychoeducational brochure. Prior to and directly following the intervention period, smoking-specific and general inhibitory control, perceived attractiveness of smoking pictures, and weekly smoking behavior were assessed. Results: Results indicated that Go/No-Go training seems to decrease evaluations of smoking stimuli rather than top-down smoking-specific and general control processes. Similar reductions for weekly smoking were found in both groups. Conclusions: Go/No-Go training did not differentially influence smoking-specific inhibitory control, general inhibitory control and weekly smoking behavior. Go/No-Go training might be able to decrease evaluations of smoking stimuli, yet based on the current study we cannot rule out the possibility of regression to the mean. More research and iterative design is needed to better understand the potential role of Go/No-Go training in smoking cessation interventions, as well as exploring other evidence-based mechanisms (e.g., peer processes, self-efficacy) that might be an important addition to smoking cessation interventions for young people. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Environmental Tobacco Smoke Exposure and Brain Functioning Associated with Smoking Cue-Reactivity and Inhibitory Control in Nonsmoking Adolescents.

INTRODUCTION: Despite its well-established negative effects, environmental tobacco smoke (ETS) exposure remains highly prevalent worldwide. ETS exposure is associated with a wide range of physical and mental health-related problems among youth, including an increased likelihood to develop nicotine dependence. Up till now, neurocognitive effects of ETS exposure are largely unknown, while such effects could explain the role of ETS exposure in the development of nicotine dependence. Therefore, this preregistered study investigated the role of current ETS exposure in brain functioning associated with smoking cue-reactivity and inhibitory control. METHOD: Concurrent with functional magnetic resonance imaging, nonsmoking adolescents aged 14-18 years (N = 51) performed a smoking cue-reactivity task, assessing brain functioning to smoking cues, and a Go/NoGo task measuring inhibitory control. ETS exposure was measured using a self-report questionnaire and biochemically verified. RESULTS: No significant associations were observed between current ETS exposure and brain functioning associated with smoking cue-reactivity and inhibitory control. CONCLUSION: These findings suggest that low-to-moderate levels of current ETS exposure are not associated with increased salience of smoking cues or deficits in inhibitory control in nonsmoking adolescents. Longitudinal research is needed to further clarify the exact effect of lifetime ETS exposure on brain functioning, as well as research focusing on the effects of higher levels of ETS exposure.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

[Fertility sparing treatment of endometrial carcinoma]. / Fertiliteitsparende behandeling endometriumcarcinoom.

BACKGROUND: The incidence of endometrial carcinoma (EC) is rising worldwide due to an increased life expectancy and obesity. Approximately 2% of patients with EC is under the age of 45. Because the incidence is also rising in young women, there is a clinical need for safe fertility sparing alternative treatments. CASE DESCRIPTION: A 32-year-old women was diagnosed with low-grade endometrioid EC. Hysteroscopic tumour resection and progestin treatment resulted in complete tumour regression. The patient became pregnant through in vitro fertilisation (IVF). CONCLUSION: This case illustrates that fertility sparing treatment, with oral progestin treatment is an alternative treatment option in selected young women with low grade, early stage endometrial carcinoma to achieve pregnancy. This treatment is internationally accepted.

Effects of environmental tobacco smoke exposure on brain functioning in never-smoking adolescents.

INTRODUCTION: Brain functioning, as indexed by event-related potentials (ERPs) representing smoking cue reactivity, inhibitory control, and reward processing, has been found to be compromised in smokers. However, whether environmental tobacco smoke (ETS) exposure in never smokers results in similar brain changes is unknown. This question is particularly relevant during adolescence, given ongoing brain maturation and a high risk of smoking initiation. The present study tested the associations between ETS exposure and ERPs reflecting cue reactivity (P3, LPP), inhibitory control (N2, P3), and reward processing (anticipation P3 (P3), feedback-related negativity (FRN)) among never-smoking adolescents. METHODS: Eighty-four never-smoking adolescents (nonexposed = 32, exposed = 52) performed a smoking cue reactivity, a Go/NoGo, and a monetary incentive delay (MID) task while ERPs were measured. RESULTS: Exposed and nonexposed groups did not differ in ERPs reflecting smoking cue reactivity, inhibitory control, and reward processing. A negative correlation between ETS exposure and the anticipatory P3 suggests reduced anticipatory reward sensitivity for nondrug rewards with increased levels of ETS exposure. However, since this effect was not consistent across analyses, no strong conclusions can be formulated. In the current study, few participants reported high levels of ETS exposure; therefore, further study is necessary. CONCLUSIONS: Nevertheless, from this study, it can be concluded that low-to-moderate exposure to ETS during adolescence does not result in functional brain changes related to smoking cue reactivity, inhibitory control, and reward processing.

Goal-Directed and Habitual Control in Smokers.

INTRODUCTION: Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding. METHODS: We used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively. RESULTS: Smokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. CONCLUSIONS: The current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems. IMPLICATIONS: Goal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not differ from controls in goal-directed versus habitual control. Individual differences in nicotine dependence within smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. These findings add to the ongoing debate on habitual versus goal-directed control in addiction and emphasize the importance of individual differences within smokers.

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

A randomized controlled trial to test the effectiveness of a peer-based social mobile game intervention to reduce smoking in youth.

Smoking is a major cause of worldwide morbidity and mortality. Almost no evidence-based intervention programs are available to help youth quit smoking. We argue that ineffective targeting of peer influence and engagement difficulties are significant barriers to successful youth smoking cessation. To address these barriers, we developed the mobile game intervention HitnRun. A two-armed randomized controlled trial (RCT; n = 144) was conducted and young smokers (Mage = 19.39; SDage = 2.52) were randomly assigned to either play HitnRun or read a psychoeducational brochure. Prior to, directly following the intervention period, and after three-month follow-up, weekly smoking behavior, abstinence rates, intervention dose, and peer- and engagement-related factors were assessed. Results indicated similar reductions in weekly smoking levels and similar abstinence rates for both groups. Yet, we found a dose effect with HitnRun only: The longer participants played HitnRun, the lower their weekly smoking levels were. In the brochure group, a higher dose was related to higher weekly smoking levels at all measurement moments. Exploratory analyses showed the most powerful effects of HitnRun for participants who connected with and were engaged by the intervention. Future work should build on the promising potential of HitnRun by increasing personalization efforts and strengthening peer influence components.

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

Do smokers devaluate smoking cues after go/no-go training?

OBJECTIVE: Smoking is one of the leading public health problems worldwide. The inability to quit smoking may be the result of the amplified value of smoking-related cues and inhibitory control deficits. Previous research has shown that pairing substance-related cues with no-go trials in go/no-go training reduces the value of these cues, an effect known as devaluation. The current experiment investigated the devaluation effect of go/no-go training on smoking-related cues, and compared this effect between smokers and nonsmokers. DESIGN AND MAIN OUTCOME MEASURES: 39 smokers and 43 nonsmokers were trained to respond immediately to neutral stimuli, but inhibit their reaction when smoking stimuli were presented. Before and after training, participants evaluated smoking and neutral stimuli, where part of these stimuli were subsequently presented in the training, and the other part was not used in training. RESULTS: Not responding to smoking stimuli in go/no-go training decreased subsequent evaluations of trained smoking stimuli compared to untrained smoking stimuli, thereby replicating food and alcohol studies and extending the devaluation effect to smoking-related cues. This devaluation effect was found for both smokers and non-smokers. CONCLUSION: Smoking-related cues can be devaluated in smokers and non-smokers, thereby showing the potential for Go/No-Go training in smoking cessation interventions.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Putamen functional connectivity during inhibitory control in smokers and non-smokers.

The putamen has been shown to play a key role in inhibitory control and addiction, and consists of distinct subregions associated with distinct functions. The anterior putamen is thought to be specialized in goal-directed control or response-monitoring in connection with frontal regions, whereas the posterior part is specialized in habitual or automatic responding in connection with sensorimotor regions. The present study is the first to delineate functional networks of the anterior and posterior putamen in a Go-NoGo response inhibition task, and to examine differences between smokers (n = 25) and non-smokers (n = 23) within these networks. Functional connectivity analyses were conducted on fMRI data from a Go-NoGo study, using the generalized form of psychophysiological interaction with anterior and posterior putamen seed regions. In the context of inhibition, the anterior putamen exhibited connectivity with the anterior cingulate cortex (ACC) and precuneus (pFWE < .05), which was in line with previous literature. Conversely, the posterior putamen showed connectivity with regions implicated in sensorimotor processing. When we compared smokers to non-smokers, we did not observe the expected weaker connectivity between the anterior putamen and ACC during inhibition in smokers. Instead, our study revealed stronger inhibition-related connectivity between the anterior putamen and right insula in smokers. This finding highlights the involvement of putamen - insula interactions in addiction and impulse control.

Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion.

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms. Methods: Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05). Results: Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.

The general relationship between internalizing psychopathology and chronic physical health conditions: a population-based study.

Studies have consistently demonstrated a reciprocal relationship between internalizing disorders and several chronic physical health conditions. Yet, much of the extant literature fails to take into account the role of comorbidity among internalizing disorders when examining the relationship with poor physical health. The current study applied latent variable modelling to investigate the shared and specific relationships between internalizing (fear and distress factors) and a range of physical health conditions. Data comprised 8841 respondents aged 16-85 years who took part in the 2007 Australian National Survey of Mental Health and Wellbeing. Multiple indicator, multiple causes models were used to parse the shared and specific relationships between internalizing disorders and variables associated with poor physical health. The study found that several physical conditions were significantly related to mean levels of fear and distress. The results were broadly similar but minor differences emerged depending on whether lifetime or past 12 months indicators of mental disorders and physical conditions were utilized in the model. Finally, the results demonstrated that the association between individual mental disorders and physical health conditions are better accounted for by indirect relationships with broad transdiagnostic dimensions rather than including additional disorder-specific relationships. The results indicate that researchers should focus on common mechanisms across multiple internalizing disorders and poor physical health when developing prevention and treatment initiatives.

Event-related potentials reflecting smoking cue reactivity and cognitive control as predictors of smoking relapse and resumption.

RATIONALE: Given that most attempts to quit smoking fail, it is critical to increase knowledge about the mechanisms involved in smoking relapse and resumption (i.e., the increase in smoking over time after a quit attempt). Neurocognitive measures, such as event-related potentials (ERPs), may provide novel insights into smoking relapse and resumption. OBJECTIVES: The objective of the present study is to investigate the association between smoking relapse and resumption and ERPs reflecting smoking cue reactivity (i.e., P300, LPP), inhibitory control (i.e., N2, P3), and error processing (i.e., error-related negativity (ERN), Pe). METHODS: Seventy-two smokers viewed smoking and neutral pictures and performed a Go-NoGo and an Eriksen Flanker task, while ERPs were measured using electroencephalography. All smokers started a quit attempt in the week following the laboratory visit. Smoking behavior after the quit attempt was measured at 4, 8, and 12 weeks. Both relapse (i.e., 7-day point prevalence at 12 weeks) and smoking resumption (i.e., the number of cigarettes a day at 4, 8, and 12 weeks) were used as outcome measures. RESULTS: Logistic regression analyses showed that smaller P3 amplitudes, reflecting brain activation associated with inhibitory control, are related to an increased relapse risk. Latent growth curve analyses showed that reduced post-error slowing, the main behavioral measure reflecting error processing, is associated with stronger smoking resumption. ERPs reflecting smoking cue reactivity were unrelated to smoking relapse or resumption. CONCLUSIONS: The finding that smaller inhibitory control-related P3 amplitudes are associated with increased relapse risks suggests that strategies to increase inhibitory control in smokers are worth further investigation in the search for more effective smoking cessation interventions.