Individuals with substance use disorders (SUDs) have to cope with drug-related cues and contexts which can affect instrumental drug seeking, as shown with Pavlovian-to-instrumental transfer (PIT) tasks among humans and animals. Our review addresses two potential mechanisms that may contribute to habitual or even compulsive drug seeking and taking. One mechanism is represented by Pavlovian and PIT effects on drug intake. The other is a shift from goal-directed to habitual drug intake, which can be accessed via model-based versus model-free decision-making in respective learning tasks. We discuss the impact of these learning mechanisms on drug consumption. First, we describe how Pavlovian and instrumental learning mechanisms interact in drug addiction. Secondly, we address the effects of acute and chronic stress exposure on behavioral and neural PIT effects in alcohol use disorder (AUD). Thirdly, we discuss how these learning mechanisms and their respective neurobiological correlates can contribute to losing versus regaining control over drug intake. Utilizing mobile technology (mobile applications on smartphones including games that measure learning mechanisms, activity bracelets), computational models, and real-world data may help to better identify patients with a high relapse risk and to offer targeted behavioral and pharmacotherapeutic interventions for vulnerable patients.

Alcohol-related aggression and violence are a widespread cause of personal suffering with high socioeconomic costs. In 2011, nearly one in three violent acts in Germany was committed under the influence of alcohol (31.8%). The link between alcohol consumption and aggression is promoted by various interacting factors. In this review, based on a selective search for pertinent literature in PubMed, we analyze and summarize information from original articles, reviews, and book chapters about alcohol and aggression and discuss the neurobiological basis of aggressive behavior. Aggression is promoted both by the cognitive deficits arising in connection with acute or chronic alcohol use and by prior experience of violence in particular situations where alcohol was drunk. Only a minority of persons who drink alcohol become aggressive. On the other hand, alcohol abuse and dependence together constitute the second most commonly diagnosed cause of suicide (15-43%). Current research indicates that the individual tendency toward alcohol-induced aggression depends not just on neurobiological factors, but also on personal expectations of the effects of alcohol, on prior experience of violent conflicts, and on the environmental conditions of early childhood, especially social exclusion and discrimination. Gene-environment interactions affecting the serotonergic and other neurotransmitter systems play an important role. Potential (but not yet adequately validated) therapeutic approaches involve reinforcing cognitive processes or pharmacologically modulating serotonergic neurotransmission (and other target processes). Alcohol-related aggression has manifold social and neurobiological causes. Specific treatments must be tested in controlled trials.

Background: Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). While there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participant characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work is difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting, and review the FDCR literature to assess the reporting of items that are deemed important.Methods: Fifty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group based on a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review.Results: By the final round, 38 items reached the consensus threshold and were classified under 7 major categories: “Participant Characteristics”, “General fMRI Information”, “General Task Information”, “Cue Information”, “Craving Assessment Inside Scanner”, “Craving Assessment Outside Scanner” and “Pre- and Post- Scanning Considerations”. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, while items in the “general fMRI reporting” category were reported in 90.5% of the reviewed papers, items in the “pre- and post-scanning considerations” category were reported by only 44.7% of reviewed FDCR studies.Conclusion: Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting, and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

Neuroscientific research in mental disorders is plagued by unclear nosological boundaries, phenotypic diversity, and high intra- and interindividual variability of identified neurobi­ological correlates. Likewise, genotypes asso­ciated with an increased risk for, e.g., schizophrenia are regularly found to also increase the risk for uni- and/or bipolar affective dis­orders. Therefore, one major research strategy of the last decade was to avoid correlation of genetic variation with complex clinical dis­orders and instead to focus on so-called intermediate or endophenotypes, i.e., neurobiological variables such as in vivo receptor expression or neuronal activation patterns, which are hypothetically more closely related to direct gene effects. We describe one such attempt and show that intermediate phenotypes such as brain activation patterns elic­ited by more or less complex cognitive tasks underlie complex regulations and influences and may thus not be the best target for neurobiological research. We suggest that in­stead of reifying brain activation as correlates of mental disorders, such disorders may best be conceptualized as results of alterations/biases in basic learning mechanisms (e.g., Pav­lovian and operant conditioning) interacting with individual and social environments and that neuroscientific research can rely on animal models and computationalized modeling to reveal their neurobiological correlates.