TY - JOUR A1 - Botteri, Edoardo A1 - Peveri, Giulia A1 - Berstad, Paula A1 - Bagnardi, Vincenzo A1 - Chen, Sairah L. F. A1 - Sandanger, Torkjel M. A1 - Hoff, Geir A1 - Dahm, Christina C. A1 - Antoniussen, Christian S. A1 - Tjonneland, Anne A1 - Eriksen, Anne Kirstine A1 - Skeie, Guri A1 - Perez-Cornago, Aurora A1 - Huerta, Jose Maria A1 - Jakszyn, Paula A1 - Harlid, Sophia A1 - Sundstroem, Bjoern A1 - Barricarte, Aurelio A1 - Monninkhof, Evelyn M. A1 - Derksen, Jeroen W. G. A1 - Schulze, Matthias Bernd A1 - Bueno-de-Mesquita, Bas A1 - Sanchez, Maria-Jose A1 - Cross, Amanda J. A1 - Tsilidis, Konstantinos K. A1 - De Magistris, Maria Santucci A1 - Kaaks, Rudolf A1 - Katzke, Verena A1 - Rothwell, Joseph A. A1 - Laouali, Nasser A1 - Severi, Gianluca A1 - Amiano, Pilar A1 - Contiero, Paolo A1 - Sacerdote, Carlotta A1 - Goldberg, Marcel A1 - Touvier, Mathilde A1 - Freisling, Heinz A1 - Viallon, Vivian A1 - Weiderpass, Elisabete A1 - Riboli, Elio A1 - Gunter, Marc J. A1 - Jenab, Mazda A1 - Ferrari, Pietro T1 - Changes in lifestyle and risk of colorectal cancer in the European prospective investigation into cancer and nutrition JF - The American journal of gastroenterology : AJG N2 - INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI <= 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention. Y1 - 2022 U6 - https://doi.org/10.14309/ajg.0000000000002065 SN - 0002-9270 SN - 1572-0241 VL - 118 IS - 4 SP - 702 EP - 711 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Sekutowicz, Maria A1 - Guggenmos, Matthias A1 - Kuitunen-Paul, Sören A1 - Garbusow, Maria A1 - Sebold, Miriam 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 - JOUR A1 - Sebold, Miriam A1 - Garbusow, Maria A1 - Jetzschmann, P. A1 - Schad, Daniel A1 - Nebe, S. A1 - Schlagenhauf, Florian A1 - Heinz, A. A1 - Rapp, Michael A. 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 - JOUR A1 - Sebold, Miriam 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 A. 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 - Schad, Daniel A1 - Garbusow, Maria A1 - Friedel, Eva A1 - Sommer, Christian A1 - Sebold, Miriam 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 A. 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 - GEN A1 - Garbusow, Maria A1 - Sommer, C. A1 - Nebe, S. A1 - Sebold, Miriam A1 - Kuitunen-Paul, Sören A1 - Wittchen, H. U. A1 - Smolka, M. A1 - Zimmermann, U. A1 - Rapp, Michael A. 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 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 A. 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 - GEN A1 - Liu, S. A1 - Kuschpel, M. S. A1 - Schad, Daniel A1 - Heinzel, Stephan A1 - Rapp, Michael A. 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 - GEN A1 - Garbusow, Maria A1 - Sommer, Christian A1 - Nebe, Stephan A1 - Sebold, Miriam A1 - Kuitunen-Paul, Sören A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael A. 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 - Schulze-Makuch, Dirk A1 - Wagner, Dirk A1 - Kounaves, Samuel P. A1 - Mangelsdorf, Kai A1 - Devine, Kevin G. A1 - de Vera, Jean-Pierre A1 - Schmitt-Kopplin, Philippe A1 - Grossart, Hans-Peter A1 - Parro, Victor A1 - Kaupenjohann, Martin A1 - Galy, Albert A1 - Schneider, Beate A1 - Airo, Alessandro A1 - Froesler, Jan A1 - Davila, Alfonso F. A1 - Arens, Felix L. A1 - Caceres, Luis A1 - Cornejo, Francisco Solis A1 - Carrizo, Daniel A1 - Dartnell, Lewis A1 - DiRuggiero, Jocelyne A1 - Flury, Markus A1 - Ganzert, Lars A1 - Gessner, Mark O. A1 - Grathwohl, Peter A1 - Guan, Lisa A1 - Heinz, Jacob A1 - Hess, Matthias A1 - Keppler, Frank A1 - Maus, Deborah A1 - McKay, Christopher P. A1 - Meckenstock, Rainer U. A1 - Montgomery, Wren A1 - Oberlin, Elizabeth A. A1 - Probst, Alexander J. A1 - Saenz, Johan S. A1 - Sattler, Tobias A1 - Schirmack, Janosch A1 - Sephton, Mark A. A1 - Schloter, Michael A1 - Uhl, Jenny A1 - Valenzuela, Bernardita A1 - Vestergaard, Gisle A1 - Woermer, Lars A1 - Zamorano, Pedro T1 - Transitory microbial habitat in the hyperarid Atacama Desert JF - Proceedings of the National Academy of Sciences of the United States of America KW - habitat KW - aridity KW - microbial activity KW - biomarker KW - Mars Y1 - 2018 U6 - https://doi.org/10.1073/pnas.1714341115 SN - 0027-8424 VL - 115 IS - 11 SP - 2670 EP - 2675 PB - National Acad. of Sciences CY - Washington ER -