Neurocognitive Insights in Nicotine Addiction

In the Netherlands, 27% of the population is currently smoking. Nicotine is among the most addictive substances of abuse. Thirty-two percent of the people who tried smoking develop nicotine dependence within ten year. This percentage is higher for nicotine than for other substances of abuse (e.g., 23 for heroin: Anthony, et al. 1994). Eighty percent of the smokers intend to quit smoking in the future while only 25% actually attempt to quit every year. Most of these quit attempts fail as 88-95% of the quitters smoke again in the year following the quit attempt (International Tobacco Control Policy Evaluation Project 2011). Although smoking rates are decreasing since 1970, the decline in smoking rates is less distinct in populations with a lower social economic status. Youngsters with lower educational levels start smoking more often and it could be that those with lower social economic status have more difficulties giving up smoking. Nicotine dependence is currently included in the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV-TR) as a ‘substance use disorder’. Examples of diagnostic criteria are tolerance, withdrawal, smoking more than one intended, and the continuation of smoking despite knowledge of adverse consequences. Although nicotine dependence is included in the DSM-IV, nicotine dependence is rarely diagnosed. In addition, many smokers do not meet the diagnostic criteria, although they do experience problems giving up smoking (Schmitz, et al. 2003) and have increased risks for serious health problems. All these characteristics of smoking imply that smoking is a serious and chronic condition that occurs in a substantial part of the population

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

A New Social Picture Task to Assess Interpretation Bias related to social fears in adolescents

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

The longitudinal link between popularity, likeability, fear of negative evaluation and social avoidance across adolescence

This study investigated the longitudinal bidirectional associations between likeability, popularity, fear of negative evaluation, and social avoidance, to aid in preventing the negative consequences and persistent trajectories of low social status and heightened social anxiety. In total, 1741 adolescents in grades 7–9 participated at 3 yearly waves. A self-report questionnaire measured fear of negative evaluation. Peer nominations assessed likeability, popularity, and social avoidance. Lower popularity predicted more avoidance, and vice versa. More avoidance was related to lower likeability over time. Being less popular and/or more liked by peers, increased fear of negative evaluation. Support for a transactional model between social anxiety and social status was found, but distinguishing different social status and social anxiety components is necessary

Cognitive control in young heavy drinkers: An ERP study

Substance use disorders have been frequently linked to an impaired cognitive control system. Whether this impaired control is also present in young adults who heavily drink alcohol is still subject to debate. The present study investigated possible impairments in cognitive control in heavy drinkers using behavioral and electrophysiological (EEG) measures. We studied behavioral performance on an inhibitory control and an error-processing task, using a GoNogo task and an Eriksen Flanker task respectively, while ERPs (Nogo-N2/P3 and ERN/Pe) were measured in a group of heavy alcohol drinkers (n = 48) and a healthy control group of light drinkers (n = 49). Results showed very few impairments in the heavy drinking group either at the behavioral or physiological level. One exception was the error-related Pe amplitude. This ERP component was reduced in heavy drinkers as compared to controls. Given that the Pe reflects a motivational component (i.e., the salience attributed to the making of errors) rather than a basic cognitive deficit, it can be concluded that heavy drinking in this population is not associated with major impaired cognitive control, but rather with impairments that are associated with aberrant attribution of salience to the making of errors. The present EEG findings are consistent with recent reviews and large scale epidemiological studies showing that heavy drinking, in contrast to substance use disorders, in young persons is not necessarily associated with major behavioral impairments in cognitive control

Carrots and sticks fail to change behavior in cocaine addiction.

Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of addicted individuals mainly rely on psychosocial approaches. Here we report on impairments in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.Sir Henry Wellcome Postdoctoral Fellowship (Grant ID: 101521/Z/12/Z)This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aaf370

Brain responses and approach bias to social alcohol cues and their association with drinking in a social setting in young adult males

Alcohol is mainly consumed in social settings, in which people often adapt their drinking behaviour to that of others, also called imitation of drinking. Yet, it remains unclear what drives this drinking in a social setting. In this study, we expected to see stronger brain and behavioural responses to social compared to non-social alcohol cues, and these responses to be associated with drinking in a social setting. The sample consisted of 153 beer-drinking males, aged 18–25 years. Brain responses to social alcohol cues were measured during an alcohol cue-exposure task performed in an fMRI scanner. Behavioural responses to social alcohol cues were measured using a stimulus-response compatibility task, providing an index of approach bias towards these cues. Drinking in a social setting was measured in a laboratory mimicking a bar environment. Specific brain responses to social alcohol cues were observed in the bilateral superior temporal sulcus and the left inferior parietal lobe. There was no approach bias towards social alcohol cues specifically; however, we did find an approach bias towards alcohol (versus soda) cues in general. Brain responses and approach bias towards social alcohol cues were unrelated and not associated with actual drinking. Thus, we found no support for a relation between drinking in a social setting on the one hand, and brain cue-reactivity or behavioural approach biases to social alcohol cues on the other hand. This suggests that, in contrast to our hypothesis, drinking in a social setting may not be driven by brain or behavioural responses to social alcohol cues

The Longitudinal Interplay Between Attention Bias and Interpretation Bias in Social Anxiety in Adolescents

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

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 &gt; 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 &gt;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 &gt; 50%) and ERPAS (27% had ERPAS &gt; 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 &gt; 50%; 64% and 78% PR-IHC &gt; 50%; 60% and 71% ERPAS &gt; 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.</p

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 &gt; 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 &gt;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 &gt; 50%) and ERPAS (27% had ERPAS &gt; 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 &gt; 50%; 64% and 78% PR-IHC &gt; 50%; 60% and 71% ERPAS &gt; 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.</p