TY - JOUR A1 - Gleich, Tobias A1 - Spitta, Gianna A1 - Butler, Oisin A1 - Zacharias, Kristin A1 - Aydin, Semiha A1 - Sebold, Miriam Hannah A1 - Garbusow, Maria A1 - Rapp, Michael Armin A1 - Schubert, Florian A1 - Buchert, Ralph A1 - Heinz, Andreas A1 - Gallinat, Jürgen T1 - Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk BT - towards a dimensional approach JF - Addiction Biology N2 - 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. KW - alcohol KW - D2/3 receptors KW - dependence KW - dopamine KW - high risk KW - PET Y1 - 2020 U6 - https://doi.org/10.1111/adb.12915 SN - 1369-1600 SN - 1355-6215 VL - 26 IS - 2 SP - 1 EP - 10 PB - Wiley-Blackwell CY - Hoboken 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 - Sebold, Miriam Hannah A1 - Deserno, Lorenz A1 - Nebe, Stefan A1 - Schad, Daniel A1 - Garbusow, Maria A1 - Haegele, Claudia A1 - Keller, Juergen A1 - Juenger, Elisabeth A1 - Kathmann, Norbert A1 - Smolka, Michael N. A1 - Rapp, Michael Armin A1 - Schlagenhauf, Florian A1 - Heinz, Andreas A1 - Huys, Quentin J. M. T1 - Model-based and model-free decisions in alcohol dependence JF - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography N2 - Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex. KW - Alcohol dependence KW - Decision-making KW - Reinforcement learning KW - Dopamine KW - Computational psychiatry Y1 - 2014 U6 - https://doi.org/10.1159/000362840 SN - 0302-282X SN - 1423-0224 VL - 70 IS - 2 SP - 122 EP - 131 PB - Karger CY - Basel ER - TY - GEN A1 - Garbusow, Maria A1 - Sommer, Christian A1 - Nebe, Stephan A1 - Sebold, Miriam Hannah A1 - Kuitunen-Paul, Sören A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael Armin A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder T2 - Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism Y1 - 2018 SN - 0145-6008 SN - 1530-0277 VL - 42 SP - 128A EP - 128A PB - Wiley CY - Hoboken 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 - Sekutowicz, Maria A1 - Guggenmos, Matthias A1 - Kuitunen-Paul, Sören A1 - Garbusow, Maria A1 - Sebold, Miriam Hannah A1 - Pelz, Patricia A1 - Priller, Josef A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Heinz, Andreas A1 - Sterzer, Philipp A1 - Schmack, Katharina T1 - Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking JF - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry N2 - BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states. KW - Alcohol dependence KW - Future drinking behavior KW - Multivoxel classification KW - Pavlovian-to-instrumental transfer KW - Relapse Y1 - 2019 U6 - https://doi.org/10.1016/j.biopsych.2019.06.028 SN - 0006-3223 SN - 1873-2402 VL - 86 IS - 11 SP - 857 EP - 863 PB - Elsevier CY - New York ER - TY - GEN A1 - Sebold, Miriam Hannah A1 - Nebe, Stephan A1 - Garbusow, Maria A1 - Schad, Daniel A1 - Sommer, Christian A1 - Rapp, Michael Armin A1 - Smolka, Michael N. A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Neurobiological correlates of learning and decision-making in alcohol dependence T2 - European psychiatry : the journal of the Association of European Psychiatrists Y1 - 2017 U6 - https://doi.org/10.1016/j.eurpsy.2017.01.084 SN - 0924-9338 SN - 1778-3585 VL - 41 SP - S11 EP - S11 PB - Elsevier CY - Paris 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 - Garbusow, Maria A1 - Nebe, Stephan A1 - Sommer, Christian A1 - Kuitunen-Paul, Sören A1 - Sebold, Miriam Hannah A1 - Schad, Daniel A1 - Friedel, Eva A1 - Veer, Ilya M. A1 - Wittchen, Hans-Ulrich A1 - Rapp, Michael Armin A1 - Ripke, Stephan A1 - Walter, Henrik A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Smolka, Michael N. A1 - Heinz, Andreas T1 - Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers BT - Behavioral, Neural and Polygenic Correlates T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 841 KW - Pavlovian-to-instrumental transfer KW - amygdala KW - alcohol KW - polygenic risk KW - high risk drinkers Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473280 SN - 1866-8364 IS - 841 ER - TY - JOUR A1 - Garbusow, Maria A1 - Nebe, Stephan A1 - Sommer, Christian A1 - Kuitunen-Paul, Sören A1 - Sebold, Miriam Hannah A1 - Schad, Daniel A1 - Friedel, Eva A1 - Veer, Ilya M. A1 - Wittchen, Hans-Ulrich A1 - Rapp, Michael Armin A1 - Ripke, Stephan A1 - Walter, Henrik A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Smolka, Michael N. A1 - Heinz, Andreas T1 - Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers BT - Behavioral, Neural and Polygenic Correlates JF - Journal of Clinical Medicine N2 - In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies. KW - Pavlovian-to-instrumental transfer KW - amygdala KW - alcohol KW - polygenic risk KW - high risk drinkers Y1 - 2019 U6 - https://doi.org/10.3390/jcm8081188 SN - 2077-0383 VL - 8 IS - 8 PB - MDPI CY - Basel ER -