TY - JOUR A1 - Heinz, A. A1 - Voss, M. A1 - Lawrie, S. M. A1 - Mishara, A. A1 - Bauer, M. A1 - Gallinat, Jürgen A1 - Juckel, G. A1 - Lang, U. A1 - Rapp, Michael Armin A1 - Falkai, P. A1 - Strik, W. A1 - Krystal, J. A1 - Abi-Dargham, A. A1 - Galderisi, S. T1 - Shall we really say goodbye to first rank symptoms? JF - European psychiatry : the journal of the Association of European Psychiatrists N2 - Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia. KW - First rank symptoms KW - Schizophrenia KW - ICD KW - DSM KW - Self-disorder Y1 - 2016 U6 - https://doi.org/10.1016/j.eurpsy.2016.04.010 SN - 0924-9338 SN - 1778-3585 VL - 37 SP - 8 EP - 13 PB - Elsevier CY - Paris ER - TY - GEN A1 - Liu, S. A1 - Kuschpel, M. S. A1 - Schad, Daniel A1 - Heinzel, Stephan A1 - Rapp, Michael Armin A1 - Heinz, A. T1 - Effects of rest on learning processes T2 - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology Y1 - 2018 U6 - https://doi.org/10.1016/j.euroneuro.2017.12.099 SN - 0924-977X SN - 1873-7862 VL - 28 SP - S67 EP - S68 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Sebold, Miriam Hannah A1 - Nebe, Stephan A1 - Garbusow, Maria A1 - Guggenmos, Matthias A1 - Schad, Daniel A1 - Beck, Anne A1 - Kuitunen-Paul, Sören A1 - Sommer, Christian A1 - Frank, Robin A1 - Neu, Peter A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael Armin A1 - Smolka, Michael N. A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - When Habits Are Dangerous: Alcohol Expectancies and Habitual Decision Making Predict Relapse in Alcohol Dependence JF - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry N2 - BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies. KW - Alcohol dependence KW - Alcohol expectancy KW - Goal-directed control KW - Medial prefrontal cortex KW - Reinforcement learning KW - Treatment outcome Y1 - 2017 U6 - https://doi.org/10.1016/j.biopsych.2017.04.019 SN - 0006-3223 SN - 1873-2402 VL - 82 SP - 847 EP - 856 PB - Elsevier CY - New York ER - TY - JOUR A1 - Schad, Daniel A1 - Garbusow, Maria A1 - Friedel, Eva A1 - Sommer, Christian A1 - Sebold, Miriam Hannah A1 - Hägele, Claudia A1 - Bernhardt, Nadine A1 - Nebe, Stephan A1 - Kuitunen-Paul, Sören A1 - Liu, Shuyan A1 - Eichmann, Uta A1 - Beck, Anne A1 - Wittchen, Hans-Ulrich A1 - Walter, Henrik A1 - Sterzer, Philipp A1 - Zimmermann, Ulrich S. A1 - Smolka, Michael N. A1 - Schlagenhauf, Florian A1 - Huys, Quentin J. M. A1 - Heinz, Andreas A1 - Rapp, Michael Armin T1 - Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk JF - European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry N2 - The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors. KW - Alcohol dependence KW - Human neuroimaging KW - Nucleus accumbens KW - Pavlovian-instrumental transfer KW - Relapse Y1 - 2018 U6 - https://doi.org/10.1007/s00406-017-0860-4 SN - 0940-1334 SN - 1433-8491 VL - 269 IS - 3 SP - 295 EP - 308 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Garbusow, Maria A1 - Schad, Daniel A1 - Sebold, Miriam Hannah A1 - Friedel, Eva A1 - Bernhardt, Nadine A1 - Koch, Stefan P. A1 - Steinacher, Bruno A1 - Kathmann, Norbert A1 - Geurts, Dirk E. M. A1 - Sommer, Christian A1 - Mueller, Dirk K. A1 - Nebe, Stephan A1 - Paul, Soeren A1 - Wittchen, Hans-Ulrich A1 - Zimmermann, Ulrich S. A1 - Walter, Henrik A1 - Smolka, Michael N. A1 - Sterzer, Philipp A1 - Rapp, Michael Armin A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence JF - Addiction biology N2 - In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. KW - human Pavlovian-to-instrumental transfer KW - nucleus accumbens KW - relapse in alcohol use disorder Y1 - 2016 U6 - https://doi.org/10.1111/adb.12243 SN - 1355-6215 SN - 1369-1600 VL - 21 SP - 719 EP - 731 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Sebold, Miriam Hannah A1 - Spitta, G. A1 - Gleich, T. A1 - Dembler-Stamm, T. A1 - Butler, Oisin A1 - Zacharias, Kristin A1 - Aydin, S. A1 - Garbusow, Maria A1 - Rapp, Michael Armin A1 - Schubert, Florian A1 - Buchert, Ralph A1 - Gallinat, Jürgen A1 - Heinz, A. T1 - Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence JF - Journal of neural transmission N2 - 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. KW - Stressful life events KW - Dopamine D2 KW - D3 receptor KW - Positron emission tomography KW - Striatum KW - Alcohol dependence Y1 - 2019 U6 - https://doi.org/10.1007/s00702-019-01985-2 SN - 0300-9564 SN - 1435-1463 VL - 126 IS - 9 SP - 1127 EP - 1134 PB - Springer CY - Wien ER - TY - JOUR A1 - Sebold, Miriam Hannah A1 - Garbusow, Maria A1 - Jetzschmann, P. A1 - Schad, Daniel A1 - Nebe, S. A1 - Schlagenhauf, Florian A1 - Heinz, A. A1 - Rapp, Michael Armin A1 - Romanczuk-Seiferth, Nina T1 - Reward and avoidance learning in the context of aversive environments and possible implications for depressive symptoms JF - Psychopharmacology N2 - 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. KW - Reward learning KW - Avoidance learning KW - Reinforcement learning KW - Computational psychiatry KW - Decision-making KW - Affective modulation KW - Depression symptoms Y1 - 2019 U6 - https://doi.org/10.1007/s00213-019-05299-9 SN - 0033-3158 SN - 1432-2072 VL - 236 IS - 8 SP - 2437 EP - 2449 PB - Springer CY - New York ER - TY - GEN A1 - Garbusow, Maria A1 - Sommer, C. A1 - Nebe, S. A1 - Sebold, Miriam Hannah A1 - Kuitunen-Paul, Sören A1 - Wittchen, H. U. A1 - Smolka, M. A1 - Zimmermann, U. A1 - Rapp, Michael Armin A1 - Huys, Q. A1 - Schlagenhauf, Florian A1 - Heinz, A. T1 - Pavlovian-instrumental transfer in the course of alcohol use disorder T2 - European psychiatry : the journal of the Association of European Psychiatrists N2 - 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. Y1 - 2018 SN - 0924-9338 SN - 1778-3585 VL - 48 SP - S546 EP - S546 PB - Elsevier CY - ISSY-LES-MOULINEAUX ER - TY - GEN A1 - Sebold, Miriam Hannah A1 - Garbusow, Maria A1 - Nebe, S. A1 - Sundmacher, L. A1 - Kuitunen-Paul, Sören A1 - Wittchen, H. U. A1 - Smolka, M. A1 - Zimmermann, U. A1 - Rapp, Michael Armin A1 - Huys, Q. A1 - Schlagenhauf, Florian A1 - Heinz, A. T1 - From goals to habits in alcohol dependence BT - association with treatment outcome and cognitive bias modification training T2 - European psychiatry : the journal of the Association of European Psychiatrists Y1 - 2018 SN - 0924-9338 SN - 1778-3585 VL - 48 SP - S274 EP - S274 PB - Elsevier CY - Paris ER - TY - JOUR A1 - Friedel, Eva A1 - Sebold, Miriam Hannah A1 - Kuitunen-Paul, Sören A1 - Nebe, Stephan A1 - Veer, Ilya M. A1 - Zimmermann, Ulrich S. A1 - Schlagenhauf, Florian A1 - Smolka, Michael N. A1 - Rapp, Michael Armin A1 - Walter, Henrik A1 - Heinz, Andreas T1 - How Accumulated Real Life Stress Experience and Cognitive Speed Interact on Decision-Making Processes JF - Frontiers in human neuroscienc N2 - Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities. KW - chronic stress KW - model-based learning KW - model-free learning KW - decision making KW - cognitive speed KW - real-life events Y1 - 2017 U6 - https://doi.org/10.3389/fnhum.2017.00302 SN - 1662-5161 VL - 11 SP - 1 EP - 9 PB - Frontiers Research Foundation CY - Lausanne ER -