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Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying F-18-fallypride positron emission tomography (F-18-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.
Introduction:
Positively conditioned Pavlovian cues tend to promote approach and negative cues promote withdrawal in a Pavlovian-to-instrumental transfer (PIT) paradigm, and the strength of this PIT effect was associated with the subsequent relapse risk in alcohol-dependent (AD) patients.
When investigating the effect of alcohol-related background cues, instrumental approach behavior was inhibited in subsequent abstainers but not relapsers. An automatic approach bias towards alcohol can be modified using a cognitive bias modification (CBM) intervention, which has previously been shown to reduce the relapse risk in AD patients. Here we examined the effects of such CBM training on PIT effects and explored its effect on the relapse risk in detoxified AD patients.
Methods:
N = 81 recently detoxified AD patients performed non-drug-related and drug-related PIT tasks before and after CBM versus placebo training. In addition, an alcohol approach/avoidance task (aAAT) was performed before and after the training to assess the alcohol approach bias. Patients were followed up for 6 months.
Results:
A stronger alcohol approach bias as well as a stronger non-drug-related PIT effect predicted relapse status in AD patients. No significant difference regarding relapse status or the number of heavy drinking days was found when comparing the CBM training group versus the placebo group.
Moreover, there was no significant modulation effect of CBM training on any PIT effect or the aAAT.
Conclusion:
A higher alcohol approach bias in the aAAT and a stronger non-drug-related PIT effect both predicted relapse in AD patients, while treatment outcome was not associated with the drug-related PIT effect. Unlike expected, CBM training did not significantly interact with the non-drug-related or the drug-related PIT effects or the alcohol approach bias.
Recent theories suggest a shift from model-based goal-directed to model-free habitual decision-making in obsessive-compulsive disorder (OCD). However, it is yet unclear, whether this shift in the decision process is heritable. We investigated 32 patients with OCD, 27 unaffected siblings (SIBs) and 31 healthy controls (HCs) using the two-step task. We computed behavioral and reaction time analyses and fitted a computational model to assess the balance between model-based and model-free control. 80 subjects also underwent structural imaging. We observed a significant ordered effect for the shift towards model-free control in the direction OCD>SIB>HC in our computational parameter of interest. However less directed analyses revealed no shift towards model-free control in OCDs. Nonetheless, we found evidence for reduced model-based control in OCDs compared to HCs and SIBs via 2nd stage reaction time analyses. In this measure SIBs also showed higher levels of model-based control than HCs. Across all subjects these effects were associated with the surface area of the left medial/right dorsolateral prefrontal cortex. Moreover, correlations between bilateral putamen/right caudate volumes and these effects varied as a function of group: they were negative in SIBs and OCDs, but positive in HCs. Associations between fronto-striatal regions and model-based reaction time effects point to a potential endophenotype for OCD.
This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.
Mobile data collection of cognitive-behavioral tasks in substance use disorders: Where are we now?
(2022)
Introduction: Over the last decades, our understanding of the cognitive, motivational, and neural processes involved in addictive behavior has increased enormously. A plethora of laboratory-based and cross-sectional studies has linked cognitive-behavioral measures to between-subject differences in drinking behavior. However, such laboratory-based studies inevitably suffer from small sample sizes and the inability to link temporal fluctuations in task measures to fluctuations in real-life substance use. To overcome these problems, several existing behavioral tasks have been transferred to smartphones to allow studying cognition in the field. Method: In this narrative review, we first summarize studies that used existing behavioral tasks in the laboratory and self-reports of substance use with ecological momentary assessment (EMA) in the field. Next, we review studies on psychometric properties of smartphone-based behavioral tasks. Finally, we review studies that used both smartphone-based tasks and self-reports with EMA in the field. Results: Overall, studies were scarce and heterogenous both in tasks and in study outcomes. Nevertheless, existing findings are promising and point toward several methodological recommendations: concerning psychometrics, studies show that - although more systematic studies are necessary - task validity and reliability can be improved, for example, by analyzing several measurement sessions at once rather than analyzing sessions separately. Studies that use tasks in the field, moreover, show that power can be improved by choosing sampling schemes that combine time-based with event-based sampling, rather than relying on time-based sampling alone. Increasing sampling frequency can further increase power. However, as this also increases the burden to participants, more research is necessary to determine the ideal sampling frequency for each task. Conclusion: Although more research is necessary to systematically study both the psychometrics of smartphone-based tasks and the frequency at which task measures fluctuate, existing studies are promising and reveal important methodological recommendations useful for researchers interested in implementing behavioral tasks in EMA studies.
Background:
Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making.
Methods:
127 subjects performed the two Step task and completed the blatant and subtle prejudice scale.
Results:
By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices.
Conclusion:
These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.
Background Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders.
Methods Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP).
Results The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: & beta; = -0.35; NVS: & beta; = 0.39; CS: & beta; = -0.12; SP: & beta; = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association.
Limitations The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for.
Conclusion Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.
Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-to-instrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.
Predictors and prevalence of hazardous alcohol use in middle-late to late adulthood in Europe
(2022)
Objectives:
Even low to moderate levels of alcohol consumption can have detrimental health consequences, especially in older adults (OA). Although many studies report an increase in the proportion of drinkers among OA, there are regional variations. Therefore, we examined alcohol consumption and the prevalence of hazardous alcohol use (HAU) among men and women aged 50+ years in four European regions and investigated predictors of HAU.
Methods:
We analyzed data of N = 35,042 participants of the European SHARE study. We investigated differences in alcohol consumption (units last week) according to gender, age and EU-region using ANOVAs. Furthermore, logistic regression models were used to examine the effect of income, education, marital status, history of a low-quality parent-child relationship and smoking on HAU, also stratified for gender and EU-region. HAU was operationalized as binge drinking or risky drinking (<12.5 units of 10 ml alcohol/week).
Results:
Overall, past week alcohol consumption was 5.0 units (+/- 7.8), prevalence of HAU was 25.4% within our sample of European adults aged 50+ years. Male gender, younger age and living in Western Europe were linked to both higher alcohol consumption and higher risks of HAU. Income, education, smoking, a low-quality parent-child relationship, living in Northern and especially Eastern Europe were positively associated with HAU. Stratified analyses revealed differences by region and gender.
Conclusions:
HAU was highly prevalent within this European sample of OA. Alcohol consumption and determinants of HAU differed between EU-regions, hinting to a necessity of risk-stratified population-level strategies to prevent HAU and subsequent alcohol use disorders.
A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects.
Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity.
In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects.
We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability.
Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting.
To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.