@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} } @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} } @article{SchadGarbusowFriedeletal.2018, author = {Schad, Daniel and Garbusow, Maria and Friedel, Eva and Sommer, Christian and Sebold, Miriam Hannah and H{\"a}gele, Claudia and Bernhardt, Nadine and Nebe, Stephan and Kuitunen-Paul, S{\"o}ren and Liu, Shuyan and Eichmann, Uta and Beck, Anne and Wittchen, Hans-Ulrich and Walter, Henrik and Sterzer, Philipp and Zimmermann, Ulrich S. and Smolka, Michael N. and Schlagenhauf, Florian and Huys, Quentin J. M. and Heinz, Andreas and Rapp, Michael Armin}, title = {Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk}, series = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry}, volume = {269}, journal = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {0940-1334}, doi = {10.1007/s00406-017-0860-4}, pages = {295 -- 308}, year = {2018}, abstract = {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.}, 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{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{HaegeleSchlagenhaufRappetal.2014, author = {H{\"a}gele, Claudia and Schlagenhauf, Florian and Rapp, Michael Armin and Sterzer, Philipp and Beck, Anne and Bermpohl, Felix and Stoy, Meline and Str{\"o}hle, Andreas and Wittchen, Hans-Ulrich and Dolan, Raymond J. and Heinz, Andreas}, title = {Dimensional psychiatry}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {653}, issn = {1866-8364}, doi = {10.25932/publishup-43106}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431064}, pages = {331 -- 341}, year = {2014}, abstract = {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.}, language = {en} } @article{GarbusowSchadSeboldetal.2016, author = {Garbusow, Maria and Schad, Daniel and Sebold, Miriam Hannah and Friedel, Eva and Bernhardt, Nadine and Koch, Stefan P. and Steinacher, Bruno and Kathmann, Norbert and Geurts, Dirk E. M. and Sommer, Christian and Mueller, Dirk K. and Nebe, Stephan and Paul, Soeren and Wittchen, Hans-Ulrich and Zimmermann, Ulrich S. and Walter, Henrik and Smolka, Michael N. and Sterzer, Philipp and Rapp, Michael Armin and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence}, series = {Addiction biology}, volume = {21}, journal = {Addiction biology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12243}, pages = {719 -- 731}, year = {2016}, abstract = {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.}, language = {en} } @article{BauerBanaschewskiHeinzetal.2016, author = {Bauer, M. and Banaschewski, Tobias and Heinz, A. and Kamp-Becker, I. and Meyer-Lindenberg, A. and Padberg, F. and Rapp, Michael Armin and Rupprecht, R. and Schneider, F. and Schulze, T. G. and Wittchen, Hans-Ulrich}, title = {The German Research Network for mental Disorders}, series = {Der Nervenarzt : Organ der Deutschen Gesellschaft f{\~A}¼r Psychiatrie, Psychotherapie und Nervenheilkunde ; Mitteilungsblatt der Deutschen Gesellschaft f{\~A}¼r Neurologie}, volume = {87}, journal = {Der Nervenarzt : Organ der Deutschen Gesellschaft f{\~A}¼r Psychiatrie, Psychotherapie und Nervenheilkunde ; Mitteilungsblatt der Deutschen Gesellschaft f{\~A}¼r Neurologie}, publisher = {Springer}, address = {New York}, issn = {0028-2804}, doi = {10.1007/s00115-016-0169-y}, pages = {989 -- 1010}, year = {2016}, abstract = {Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 \% of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 \%. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.}, language = {de} } @article{HaegeleSchlagenhaufRappetal.2015, author = {Haegele, Claudia and Schlagenhauf, Florian and Rapp, Michael Armin and Sterzer, Philipp and Beck, Anne and Bermpohl, Felix and Stoy, Meline and Stroehle, Andreas and Wittchen, Hans-Ulrich and Dolan, Raymond J. and Heinz, Andreas}, title = {Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders}, series = {Psychopharmacology}, volume = {232}, journal = {Psychopharmacology}, number = {2}, publisher = {Springer}, address = {New York}, issn = {0033-3158}, doi = {10.1007/s00213-014-3662-7}, pages = {331 -- 341}, year = {2015}, abstract = {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. 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.}, language = {en} }