@article{DeekenReichertZechetal.2022, author = {Deeken, Friederike and Reichert, Markus and Zech, Hilmar and Wenzel, Julia and Wedemeyer, Friederike and Aguilera, Alvaro and Aslan, Acelya and Bach, Patrick and Bahr, Nadja Samia and Ebrahimi, Claudia and Fischbach, Pascale Christine and Ganz, Marvin and Garbusow, Maria and Großkopf, Charlotte M. and Heigert, Marie and Hentschel, Angela and Karl, Damian and Pelz, Patricia and Pinger, Mathieu and Riemerschmid, Carlotta and Rosenthal, Annika and Steffen, Johannes and Strehle, Jens and Weiss,, Franziska and Wieder, Gesine and Wieland, Alfred and Zaiser, Judith and Zimmermann, Sina and Walter, Henrik and Lenz, Bernd and Deserno, Lorenz and Smolka, Michael N. and Liu, Shuyan and Ebner-Priemer, Ulrich Walter and Heinz, Andreas and Rapp, Michael Armin}, title = {Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany}, series = {JAMA Network Open}, volume = {5}, journal = {JAMA Network Open}, edition = {8}, publisher = {JAMA Network / American Medical Association}, address = {Chicago, Illinois, USA}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2022.24641}, pages = {1 -- 11}, year = {2022}, abstract = {Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0\%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95\% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95\% CI, 21.87-31.77; P < .001) and New Year's Eve (β = 66.88; 95\% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95\% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = -5.45; 95\% CI, -8.00 to -2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = -11.10; 95\% CI, -13.63 to -8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = -6.14; 95\% CI, -9.96 to -2.31; P = .002) and in participants with severe AUD (β = -6.26; 95\% CI, -10.18 to -2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.}, language = {en} } @article{ChenHollunderGarbusowetal.2020, author = {Chen, Ke and Hollunder, Barbara and Garbusow, Maria and Sebold, Miriam Hannah and Heinz, Andreas}, title = {The physiological responses to acute stress in alcohol-dependent patients}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {41}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2020.09.003}, pages = {1 -- 15}, year = {2020}, abstract = {Dysregulation of physiological stress reactivity plays a key role in the development and relapse risk of alcohol dependence. This article reviews studies investigating physiological responses to experimentally induced acute stress in patients with alcohol dependence. A systematic search from electronic databases resulted in 3641 articles found and after screening 62 articles were included in our review. Studies are analyzed based on stress types (i.e., social stress tasks and nonsocial stress tasks) and physiological markers (i.e., the nervous system, the endocrine system, somatic responses and the immune system). In studies applying nonsocial stress tasks, alcohol-dependent patients were reported to show a blunted stress response compared with healthy controls in the majority of studies applying markers of adrenocorticotropic hormone and cortisol. In studies applying social stress tasks, findings are inconsistent, with less than half of the studies reporting altered physiological stress responses in patients. We discuss the impact of duration of abstinence, comorbidities, baseline physiological arousal and intervention on the discrepancy of study findings. Furthermore, we review evidence for an associationbetween blunted physiological stress responses and the relapse risk among patients with alcohol dependence. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)}, language = {en} } @article{ChenNebeMojtahedzadehetal.2020, author = {Chen, Hao and Nebe, Stephan and Mojtahedzadeh, Negin and Kuitunen-Paul, Soren and Garbusow, Maria and Schad, Daniel and Rapp, Michael Armin and Huys, Quentin J. M. and Heinz, Andreas and Smolka, Michael N.}, title = {Susceptibility to interference between Pavlovian and instrumental control is associated with early hazardous alcohol use}, series = {Addiction biology}, volume = {26}, journal = {Addiction biology}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12983}, pages = {1 -- 14}, year = {2020}, abstract = {Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.}, language = {en} } @misc{ChenNebeMojtahedzadehetal.2020, author = {Chen, Hao and Nebe, Stephan and Mojtahedzadeh, Negin and Kuitunen-Paul, Soren and Garbusow, Maria and Schad, Daniel and Rapp, Michael Armin and Huys, Quentin J. M. and Heinz, Andreas and Smolka, Michael N.}, title = {Susceptibility to interference between Pavlovian and instrumental control is associated with early hazardous alcohol use}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {4}, issn = {1866-8364}, doi = {10.25932/publishup-56960}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-569609}, pages = {16}, year = {2020}, abstract = {Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.}, language = {en} } @article{SekutowiczGuggenmosKuitunenPauletal.2019, author = {Sekutowicz, Maria and Guggenmos, Matthias and Kuitunen-Paul, S{\"o}ren and Garbusow, Maria and Sebold, Miriam Hannah and Pelz, Patricia and Priller, Josef and Wittchen, Hans-Ulrich and Smolka, Michael N. and Zimmermann, Ulrich S. and Heinz, Andreas and Sterzer, Philipp and Schmack, Katharina}, title = {Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking}, series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, volume = {86}, journal = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, number = {11}, publisher = {Elsevier}, address = {New York}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2019.06.028}, pages = {857 -- 863}, year = {2019}, abstract = {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.}, language = {en} } @misc{GarbusowNebeSommeretal.2019, author = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam Hannah and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael Armin and Ripke, Stephan and Walter, Henrik and Huys, Quentin J. M. and Schlagenhauf, Florian and Smolka, Michael N. and Heinz, Andreas}, title = {Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {841}, issn = {1866-8364}, doi = {10.25932/publishup-47328}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-473280}, pages = {14}, year = {2019}, abstract = {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.}, language = {en} } @article{SeboldGarbusowJetzschmannetal.2019, author = {Sebold, Miriam Hannah and Garbusow, Maria and Jetzschmann, P. and Schad, Daniel and Nebe, S. and Schlagenhauf, Florian and Heinz, A. and Rapp, Michael Armin and Romanczuk-Seiferth, Nina}, title = {Reward and avoidance learning in the context of aversive environments and possible implications for depressive symptoms}, series = {Psychopharmacology}, volume = {236}, journal = {Psychopharmacology}, number = {8}, publisher = {Springer}, address = {New York}, issn = {0033-3158}, doi = {10.1007/s00213-019-05299-9}, pages = {2437 -- 2449}, year = {2019}, abstract = {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.}, language = {en} } @article{GarbusowNebeSommeretal.2019, author = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam Hannah and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael Armin and Ripke, Stephan and Walter, Henrik and Huys, Quentin J. M. and Schlagenhauf, Florian and Smolka, Michael N. and Heinz, Andreas}, title = {Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers}, series = {Journal of Clinical Medicine}, volume = {8}, journal = {Journal of Clinical Medicine}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {2077-0383}, doi = {10.3390/jcm8081188}, pages = {14}, year = {2019}, abstract = {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.}, language = {en} } @article{SeboldSpittaGleichetal.2019, author = {Sebold, Miriam Hannah and Spitta, G. and Gleich, T. and Dembler-Stamm, T. and Butler, Oisin and Zacharias, Kristin and Aydin, S. and Garbusow, Maria and Rapp, Michael Armin and Schubert, Florian and Buchert, Ralph and Gallinat, J{\"u}rgen and Heinz, A.}, title = {Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence}, series = {Journal of neural transmission}, volume = {126}, journal = {Journal of neural transmission}, number = {9}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-019-01985-2}, pages = {1127 -- 1134}, year = {2019}, abstract = {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.}, language = {en} } @misc{GarbusowSommerNebeetal.2018, author = {Garbusow, Maria and Sommer, Christian and Nebe, Stephan and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Wittchen, Hans-Ulrich and Smolka, Michael N. and Zimmermann, Ulrich S. and Rapp, Michael Armin and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder}, series = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, volume = {42}, journal = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, publisher = {Wiley}, address = {Hoboken}, issn = {0145-6008}, pages = {128A -- 128A}, year = {2018}, language = {en} }