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  - 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  - 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  - 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  - 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  - 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  - 
TY  - JOUR
A1  - Garbusow, Maria
A1  - Schad, Daniel
A1  - Sebold, Miriam Hannah
A1  - Friedel, Eva
A1  - Bernhardt, Nadine
A1  - Koch, Stefan P.
A1  - Steinacher, Bruno
A1  - Kathmann, Norbert
A1  - Geurts, Dirk E. M.
A1  - Sommer, Christian
A1  - Mueller, Dirk K.
A1  - Nebe, Stephan
A1  - Paul, Soeren
A1  - Wittchen, Hans-Ulrich
A1  - Zimmermann, Ulrich S.
A1  - Walter, Henrik
A1  - Smolka, Michael N.
A1  - Sterzer, Philipp
A1  - Rapp, Michael Armin
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence
JF  - Addiction biology
N2  - 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.
KW  - human Pavlovian-to-instrumental transfer
KW  - nucleus accumbens
KW  - relapse in alcohol use disorder
Y1  - 2016
U6  - https://doi.org/10.1111/adb.12243
SN  - 1355-6215
SN  - 1369-1600
VL  - 21
SP  - 719
EP  - 731
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Nebe, Stephan
A1  - Garbusow, Maria
A1  - Guggenmos, Matthias
A1  - Schad, Daniel
A1  - Beck, Anne
A1  - Kuitunen-Paul, Sören
A1  - Sommer, Christian
A1  - Frank, Robin
A1  - Neu, Peter
A1  - Zimmermann, Ulrich S.
A1  - Rapp, Michael Armin
A1  - Smolka, Michael N.
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - When Habits Are Dangerous: Alcohol Expectancies and Habitual Decision Making Predict Relapse in Alcohol Dependence
JF  - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry
N2  - BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
KW  - Alcohol dependence
KW  - Alcohol expectancy
KW  - Goal-directed control
KW  - Medial prefrontal cortex
KW  - Reinforcement learning
KW  - Treatment outcome
Y1  - 2017
U6  - https://doi.org/10.1016/j.biopsych.2017.04.019
SN  - 0006-3223
SN  - 1873-2402
VL  - 82
SP  - 847
EP  - 856
PB  - Elsevier
CY  - New York
ER  -