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Garbusow, Maria ; Sommer, Christian ; Nebe, Stephan ; Sebold, Miriam ; Kuitunen-Paul, Sören ; Wittchen, Hans-Ulrich ; Smolka, Michael N. ; Zimmermann, Ulrich S. ; Rapp, Michael A. ; Huys, Quentin J. M. ; Schlagenhauf, Florian ; Heinz, Andreas
Schulze-Makuch, Dirk ; Wagner, Dirk ; Kounaves, Samuel P. ; Mangelsdorf, Kai ; Devine, Kevin G. ; de Vera, Jean-Pierre ; Schmitt-Kopplin, Philippe ; Grossart, Hans-Peter ; Parro, Victor ; Kaupenjohann, Martin ; Galy, Albert ; Schneider, Beate ; Airo, Alessandro ; Froesler, Jan ; Davila, Alfonso F. ; Arens, Felix L. ; Caceres, Luis ; Cornejo, Francisco Solis ; Carrizo, Daniel ; Dartnell, Lewis ; DiRuggiero, Jocelyne ; Flury, Markus ; Ganzert, Lars ; Gessner, Mark O. ; Grathwohl, Peter ; Guan, Lisa ; Heinz, Jacob ; Hess, Matthias ; Keppler, Frank ; Maus, Deborah ; McKay, Christopher P. ; Meckenstock, Rainer U. ; Montgomery, Wren ; Oberlin, Elizabeth A. ; Probst, Alexander J. ; Saenz, Johan S. ; Sattler, Tobias ; Schirmack, Janosch ; Sephton, Mark A. ; Schloter, Michael ; Uhl, Jenny ; Valenzuela, Bernardita ; Vestergaard, Gisle ; Woermer, Lars ; Zamorano, Pedro
Sebold, Miriam ; Spitta, G. ; Gleich, T. ; Dembler-Stamm, T. ; Butler, Oisin ; Zacharias, Kristin ; Aydin, S. ; Garbusow, Maria ; Rapp, Michael A. ; Schubert, Florian ; Buchert, Ralph ; Gallinat, Jürgen ; Heinz, Andreas
Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction.
Garbusow, Maria ; Sommer, C. ; Nebe, S. ; Sebold, Miriam ; Kuitunen-Paul, Sören ; Wittchen, H. U. ; Smolka, M. ; Zimmermann, U. ; Rapp, Michael A. ; Huys, Q. ; Schlagenhauf, Florian ; Heinz, Andreas
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol
dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer.
Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks.
Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs.
Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Sebold, Miriam ; Garbusow, Maria ; Jetzschmann, P. ; Schad, Daniel ; Nebe, S. ; Schlagenhauf, Florian ; Heinz, Andreas ; Rapp, Michael A. ; Romanczuk-Seiferth, Nina
Background Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. Methods To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Results Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Conclusion Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.