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 - 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 - 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 - Kaminski, Jakob A. A1 - Schlagenhauf, Florian A1 - Rapp, Michael Armin A1 - Awasthi, Swapnil A1 - Ruggeri, Barbara A1 - Deserno, Lorenz A1 - Banaschewski, Tobias A1 - Bokde, Arun L. W. A1 - Bromberg, Uli A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivières, Sylvane A1 - Flor, Herta A1 - Frouin, Vincent A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Paillère Martinot, Marie-Laure A1 - Nees, Frauke A1 - Papadopoulos Orfanos, Dimitri A1 - Paus, Tomáš A1 - Poustka, Luise A1 - Smolka, Michael N. A1 - Fröhner, Juliane H. A1 - Walter, Henrik A1 - Whelan, Robert A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - Epigenetic variance in dopamine D2 receptor BT - a marker of IQ malleability? T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 950 KW - genome-wide association KW - reward anticipation KW - human intelligence KW - human brain KW - stress KW - metaanalysis KW - striatum KW - psychopathology KW - prediction KW - volume KW - epigenetics and behaviour KW - human behaviour KW - learning and memory Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-425687 SN - 1866-8372 IS - 950 ER - TY - GEN A1 - Kaminski, Jakob A1 - Schlagenhauf, Florian A1 - Rapp, Michael Armin A1 - Awasthi, Swapnil A1 - Ruggeri, Barbara A1 - Deserno, Lorenz A1 - Laura, Daedelow A1 - Banaschewski, Tobias A1 - Bokde, Arun A1 - Quinlan, Erin Burke A1 - Buechel, Christian A1 - Bromberg, Uli A1 - Desrivieres, Sylvane A1 - Flor, Herta A1 - Frouin, Vincent A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Martinot, Marie-Laure Paillere A1 - Nees, Frauke A1 - Orfanos, Dimitri Papadopoulos A1 - Paus, Tomas A1 - Poustka, Luise A1 - Smolka, Michael A1 - Froehner, Juliane A1 - Walter, Henrik A1 - Whelan, Robert A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - Variance in Dopaminergic Markers BT - a possible marker of individual differences in IQ? T2 - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry KW - Intelligence KW - Dopamine KW - Epigenetic Biomarkers KW - Reward Anticipation KW - Polygenic Risk Score Y1 - 2018 U6 - https://doi.org/10.1016/j.biopsych.2018.02.311 SN - 0006-3223 SN - 1873-2402 VL - 83 IS - 9 SP - S118 EP - S118 PB - Elsevier CY - New York ER - TY - GEN A1 - Awasthi, Swapnil A1 - Kaminski, Jakob A1 - Rapp, Michael Armin A1 - Schlagenhauf, Florian A1 - Walter, Henrik A1 - Ruggeri, Barbara A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - A neural signature of malleability BT - general intelligence correlates with ventral striatal activation and epigenetic makers of dopamine neurotransmission T2 - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - General intelligence has a substantial genetic background in children, adolescents, and adults, but environmental factors also strongly correlate with cognitive performance as evidenced by a strong (up to one SD) increase in average intelligence test results in the second half of the previous century. This change occurred in a period apparently too short to accommodate radical genetic changes. It is highly suggestive that environmental factors interact with genotype by possible modification of epigenetic factors that regulate gene expression and thus contribute to individual malleability. This modification might as well be reflected in recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. Y1 - 2019 U6 - https://doi.org/10.1016/j.euroneuro.2017.08.139 SN - 0924-977X SN - 1873-7862 VL - 29 SP - S858 EP - S859 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Deserno, Lorenz A1 - Beck, Anne A1 - Huys, Quentin J. M. A1 - Lorenz, Robert C. A1 - Buchert, Ralph A1 - Buchholz, Hans-Georg A1 - Plotkin, Michail A1 - Kumakara, Yoshitaka A1 - Cumming, Paul A1 - Heinze, Hans-Jochen A1 - Grace, Anthony A. A1 - Rapp, Michael Armin A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum JF - European journal of neuroscience N2 - Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake. KW - alcohol addiction KW - dopamine KW - fMRI KW - PET KW - prediction error Y1 - 2015 U6 - https://doi.org/10.1111/ejn.12802 SN - 0953-816X SN - 1460-9568 VL - 41 IS - 4 SP - 477 EP - 486 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Kaminski, Jakob A. A1 - Schlagenhauf, Florian A1 - Rapp, Michael Armin A1 - Awasthi, Swapnil A1 - Ruggeri, Barbara A1 - Deserno, Lorenz A1 - Banaschewski, Tobias A1 - Bokde, Arun L. W. A1 - Bromberg, Uli A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivieres, Sylvane A1 - Flor, Herta A1 - Frouin, Vincent A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Martinot, Marie-Laure Paillere A1 - Nees, Frauke A1 - Orfanos, Dimitri Papadopoulos A1 - Paus, Tomas A1 - Poustka, Luise A1 - Smolka, Michael N. A1 - Fröhner, Juliane H. A1 - Walter, Henrik A1 - Whelan, Robert A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - Epigenetic variance in dopamine D2 receptor BT - a marker of IQ malleability? JF - Translational Psychiatry N2 - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure. Y1 - 2018 U6 - https://doi.org/10.1038/s41398-018-0222-7 SN - 2158-3188 VL - 8 PB - Nature Publ. Group CY - New York ER - TY - GEN A1 - Hägele, Claudia A1 - Schlagenhauf, Florian A1 - Rapp, Michael Armin A1 - Sterzer, Philipp A1 - Beck, Anne A1 - Bermpohl, Felix A1 - Stoy, Meline A1 - Ströhle, Andreas A1 - Wittchen, Hans-Ulrich A1 - Dolan, Raymond J. A1 - Heinz, Andreas T1 - Dimensional psychiatry BT - reward dysfunction and depressive mood across psychiatric disorders T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries. We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment. We used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects' individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation. During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation. Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 653 KW - dimensional KW - fMRI KW - reward system KW - ventral striatum KW - monetary incentive delay task KW - depressive symptoms Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-431064 SN - 1866-8364 IS - 653 SP - 331 EP - 341 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 -