@article{FrodlJanowitzSchmaaletal.2017, author = {Frodl, Thomas and Janowitz, Deborah and Schmaal, Lianne and Tozzi, Leonardo and Dobrowolny, Henrik and Stein, Dan J. and Veltman, Dick J. and Wittfeld, Katharina and van Erp, Theo G. M. and Jahanshad, Neda and Block, Andrea and Hegenscheid, Katrin and Voelzke, Henry and Lagopoulos, Jim and Hatton, Sean N. and Hickie, Ian B. and Frey, Eva Maria and Carballedo, Angela and Brooks, Samantha J. and Vuletic, Daniella and Uhlmann, Anne and Veer, Ilya M. and Walter, Henrik and Schnell, Knut and Grotegerd, Dominik and Arolt, Volker and Kugel, Harald and Schramm, Elisabeth and Konrad, Carsten and Zurowski, Bartosz and Baune, Bernhard T. and van der Wee, Nic J. A. and van Tol, Marie-Jose and Penninx, Brenda W. J. H. and Thompson, Paul M. and Hibar, Derrek P. and Dannlowski, Udo and Grabe, Hans J.}, title = {Childhood adversity impacts on brain subcortical structures relevant to depression}, series = {Journal of psychiatric research}, volume = {86}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2016.11.010}, pages = {58 -- 65}, year = {2017}, abstract = {Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. (C) 2016 Published by Elsevier Ltd.}, language = {en} } @misc{DeekenReichertZechetal., 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 A.}, title = {Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {805}, issn = {1866-8364}, doi = {10.25932/publishup-57146}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-571460}, pages = {11}, 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{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 A.}, 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} } @misc{XieJiaRollsetal.2021, author = {Xie, Chao and Jia, Tianye and Rolls, Edmund T. and Robbins, Trevor W. and Sahakian, Barbara J. and Zhang, Jie and Liu, Zhaowen and Cheng, Wei and Luo, Qiang and Zac Lo, Chun-Yi and Schumann, Gunter and Feng, Jianfeng and Wang, He and Banaschewski, Tobias and Barker, Gareth J. and Bokde, Arun L.W. and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivi{\`e}res, Sylvane and Flor, Herta and Grigis, Antoine and Garavan, Hugh and Gowland, Penny and Heinz, Andreas and Hohmann, Sarah and Ittermann, Bernd and Martinot, Jean-Luc and Paill{\`e}re Martinot, Marie-Laure and Nees, Frauke and Papadopoulos Orfanos, Dimitri and Paus, Tom{\´a}š and Poustka, Luise and Fr{\"o}hner, Juliane H. and Smolka, Michael N. and Walter, Henrik and Whelan, Robert}, title = {Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {3}, issn = {1866-8364}, doi = {10.25932/publishup-55788}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-557882}, pages = {13}, year = {2021}, abstract = {BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.}, language = {en} } @misc{StelzelBohleSchauenburgetal.2018, author = {Stelzel, Christine and Bohle, Hannah and Schauenburg, Gesche and Walter, Henrik and Granacher, Urs and Rapp, Michael A. and Heinzel, Stephan}, title = {Contribution of the Lateral Prefrontal Cortex to Cognitive-Postural Multitasking}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {489}, issn = {1866-8364}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-421140}, pages = {12}, year = {2018}, abstract = {There is evidence for cortical contribution to the regulation of human postural control. Interference from concurrently performed cognitive tasks supports this notion, and the lateral prefrontal cortex (lPFC) has been suggested to play a prominent role in the processing of purely cognitive as well as cognitive-postural dual tasks. The degree of cognitive-motor interference varies greatly between individuals, but it is unresolved whether individual differences in the recruitment of specific lPFC regions during cognitive dual tasking are associated with individual differences in cognitive-motor interference. Here, we investigated inter-individual variability in a cognitive-postural multitasking situation in healthy young adults (n = 29) in order to relate these to inter-individual variability in lPFC recruitment during cognitive multitasking. For this purpose, a oneback working memory task was performed either as single task or as dual task in order to vary cognitive load. Participants performed these cognitive single and dual tasks either during upright stance on a balance pad that was placed on top of a force plate or during fMRI measurement with little to no postural demands. We hypothesized dual one-back task performance to be associated with lPFC recruitment when compared to single one-back task performance. In addition, we expected individual variability in lPFC recruitment to be associated with postural performance costs during concurrent dual one-back performance. As expected, behavioral performance costs in postural sway during dual-one back performance largely varied between individuals and so did lPFC recruitment during dual one-back performance. Most importantly, individuals who recruited the right mid-lPFC to a larger degree during dual one-back performance also showed greater postural sway as measured by larger performance costs in total center of pressure displacements. This effect was selective to the high-load dual one-back task and suggests a crucial role of the right lPFC in allocating resources during cognitivemotor interference. Our study provides further insight into the mechanisms underlying cognitive-motor multitasking and its impairments.}, language = {en} } @misc{KaminskiSchlagenhaufRappetal.2018, author = {Kaminski, Jakob A. and Schlagenhauf, Florian and Rapp, Michael A. and Awasthi, Swapnil and Ruggeri, Barbara and Deserno, Lorenz and Banaschewski, Tobias and Bokde, Arun L. W. and Bromberg, Uli and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivi{\`e}res, Sylvane and Flor, Herta and Frouin, Vincent and Garavan, Hugh and Gowland, Penny and Ittermann, Bernd and Martinot, Jean-Luc and Paill{\`e}re Martinot, Marie-Laure and Nees, Frauke and Papadopoulos Orfanos, Dimitri and Paus, Tom{\´a}š and Poustka, Luise and Smolka, Michael N. and Fr{\"o}hner, Juliane H. and Walter, Henrik and Whelan, Robert and Ripke, Stephan and Schumann, Gunter and Heinz, Andreas}, title = {Epigenetic variance in dopamine D2 receptor}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {950}, issn = {1866-8372}, doi = {10.25932/publishup-42568}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-425687}, pages = {13}, year = {2018}, abstract = {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.}, language = {en} } @misc{GarbusowNebeSommeretal.2019, author = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael A. 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{StelzelBohleSchauenburgetal.2018, author = {Stelzel, Christine and Bohle, Hannah and Schauenburg, Gesche and Walter, Henrik and Granacher, Urs and Rapp, Michael A. and Heinzel, Stephan}, title = {Contribution of the Lateral Prefrontal Cortex to Cognitive-Postural Multitasking}, series = {Frontiers in psychologie}, volume = {9}, journal = {Frontiers in psychologie}, publisher = {Frontiers}, address = {Lausanne}, issn = {1664-1078}, doi = {10.3389/fpsyg.2018.01075}, pages = {12}, year = {2018}, abstract = {There is evidence for cortical contribution to the regulation of human postural control. Interference from concurrently performed cognitive tasks supports this notion, and the lateral prefrontal cortex (lPFC) has been suggested to play a prominent role in the processing of purely cognitive as well as cognitive-postural dual tasks. The degree of cognitive-motor interference varies greatly between individuals, but it is unresolved whether individual differences in the recruitment of specific lPFC regions during cognitive dual tasking are associated with individual differences in cognitive-motor interference. Here, we investigated inter-individual variability in a cognitive-postural multitasking situation in healthy young adults (n = 29) in order to relate these to inter-individual variability in lPFC recruitment during cognitive multitasking. For this purpose, a oneback working memory task was performed either as single task or as dual task in order to vary cognitive load. Participants performed these cognitive single and dual tasks either during upright stance on a balance pad that was placed on top of a force plate or during fMRI measurement with little to no postural demands. We hypothesized dual one-back task performance to be associated with lPFC recruitment when compared to single one-back task performance. In addition, we expected individual variability in lPFC recruitment to be associated with postural performance costs during concurrent dual one-back performance. As expected, behavioral performance costs in postural sway during dual-one back performance largely varied between individuals and so did lPFC recruitment during dual one-back performance. Most importantly, individuals who recruited the right mid-lPFC to a larger degree during dual one-back performance also showed greater postural sway as measured by larger performance costs in total center of pressure displacements. This effect was selective to the high-load dual one-back task and suggests a crucial role of the right lPFC in allocating resources during cognitivemotor interference. Our study provides further insight into the mechanisms underlying cognitive-motor multitasking and its impairments.}, language = {en} } @article{SchadGarbusowFriedeletal.2018, author = {Schad, Daniel and Garbusow, Maria and Friedel, Eva and Sommer, Christian and Sebold, Miriam 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 A.}, 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{KaminskiSchlagenhaufRappetal.2018, author = {Kaminski, Jakob A. and Schlagenhauf, Florian and Rapp, Michael A. and Awasthi, Swapnil and Ruggeri, Barbara and Deserno, Lorenz and Banaschewski, Tobias and Bokde, Arun L. W. and Bromberg, Uli and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivieres, Sylvane and Flor, Herta and Frouin, Vincent and Garavan, Hugh and Gowland, Penny and Ittermann, Bernd and Martinot, Jean-Luc and Martinot, Marie-Laure Paillere and Nees, Frauke and Orfanos, Dimitri Papadopoulos and Paus, Tomas and Poustka, Luise and Smolka, Michael N. and Fr{\"o}hner, Juliane H. and Walter, Henrik and Whelan, Robert and Ripke, Stephan and Schumann, Gunter and Heinz, Andreas}, title = {Epigenetic variance in dopamine D2 receptor}, series = {Translational Psychiatry}, volume = {8}, journal = {Translational Psychiatry}, publisher = {Nature Publ. Group}, address = {New York}, organization = {IMAGEN Consortium}, issn = {2158-3188}, doi = {10.1038/s41398-018-0222-7}, pages = {11}, year = {2018}, abstract = {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.}, language = {en} }