@article{BuchmannSchmidBlomeyeretal.2009, author = {Buchmann, Arlette F. and Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Treutlein, Jens and Zimmermann, Ulrich S. and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Rietschel, Marcella and Schumann, Gunter and Laucht, Manfred}, title = {Impact of age at first drink on vulnerability to alcohol-related problems : testing the marker hypothesis in a prospective study of young adults}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2009.02.006}, year = {2009}, abstract = {There is ample evidence that the early initiation of alcohol use is a risk factor for the development of later alcohol-related problems. The purpose of the current study was to examine whether this association can be explained by indicators of a common underlying susceptibility or whether age at drinking onset may be considered as an independent predictor of later drinking behavior, suggesting a potential causal relationship. Participants were drawn from a prospective cohort study of the long-term outcomes of early risk factors followed up from birth onwards. Structured interviews were administered to 304 participants to assess age at first drink and current drinking behavior. Data on risk factors, including early family adversity, parental alcohol use, childhood psychopathology and stressful life events, were repeatedly collected during childhood using standardized parent interviews. In addition, information on genotype was considered. Results confirmed previous work demonstrating that hazardous alcohol consumption is related to early-adolescent drinking onset. A younger age of first drink was significantly predicted by 5-HTTLPR genotype and the degree of preceding externalizing symptoms, and both factors were related to increased consumption or harmful alcohol use at age 19. However, even after controlling for these potential explanatory factors, earlier age at drinking onset remained a strong predictor of heavy alcohol consumption in young adulthood. The present longitudinal study adds to the current literature indicating that the early onset - adult hazardous drinking association cannot solely be attributed to shared genetic and psychopathologic risk factors as examined in this study.}, language = {en} } @article{BlomeyerTreutleinEsseretal.2007, author = {Blomeyer, Dorothea and Treutlein, Jens and Esser, G{\"u}nter and Schmidt, Martin H. and Schumann, Gunter and Laucht, Manfred}, title = {Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use}, issn = {0006-3223}, year = {2007}, abstract = {Background: Recent animal research suggests that alterations in the corticotropin releasing hormone receptor 1 (CRHR1) may lead to heavy alcohol use following repeated stress. The aim of this study was to examine interactions between two haplotype-tagging single nucleotide polymorphisms (SNPs) covering the CRHR1 gene and adverse life events on heavy drinking in adolescents. Methods: Data were available from the Mannheim Study of Children at Risk, an ongoing cohort study of the long-term outcome of early risk factors followed since birth. At age 15 years, 280 participants (135 males, 145 females) completed a self-report questionnaire measuring alcohol use and were genotyped for two SNPs (rs242938, rs1876831) of CRHR1. Assessment of negative life events over the past three years was obtained by a standardized interview with the parents. Results: Adolescents homozygous for the C allele of rs1876831 drank higher maximum amounts of alcohol per occasion and had greater lifetime rates of heavy drinking in relation to negative life events than individuals carrying the T allele. No gene X environment interactions were found for regular drinking and between rs242938 and stressful life events. Conclusions: These findings provide first evidence in humans that the CRHR1 gene interacts with exposure to stressful life events to predict heavy alcohol use in adolescents.}, language = {en} } @article{HolzBoeckerSchlierBuchmannetal.2017, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Baumeister, Sarah and Plichta, Michael M. and Cattrell, Anna and Schumann, Gunter and Esser, G{\"u}nter and Schmidt, Martin and Buitelaar, Jan and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder}, series = {Frontiers in human neuroscience}, volume = {12}, journal = {Frontiers in human neuroscience}, number = {2}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsw120}, pages = {261 -- 272}, year = {2017}, abstract = {Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors.}, language = {en} } @article{BlomeyerBuchmannLascorzetal.2013, author = {Blomeyer, Dorothea and Buchmann, Arlette F. and Lascorz, Jesus and Zimmermann, Ulrich S. and Esser, G{\"u}nter and Desrivieres, Sylvane and Schmidt, Martin H. and Banaschewski, Tobias and Schumann, Gunter and Laucht, Manfred}, title = {Association of PER2 genotype and stressful life events with alcohol drinking in young adults}, series = {PLoS one}, volume = {8}, journal = {PLoS one}, number = {3}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0059136}, pages = {7}, year = {2013}, abstract = {Background: Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking. Methods: Data were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview. Results: Individuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72\% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress. Conclusions: These findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.}, language = {en} } @article{LauchtBeckerFranketal.2008, author = {Laucht, Manfred and Becker, Katja and Frank, Josef and Schmidt, Martin H. and Esser, G{\"u}nter and Treutlein, Jens and Skowronek, Markus H. and Schumann, Gunter}, title = {Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence}, issn = {0890-8567}, doi = {10.1097/Chi.0b013e31816bff77}, year = {2008}, abstract = {Objective: To clarify the nature of the association between dopamine genes and smoking by examining whether genetic variability in components of the dopamine pathway could explain refined phenotypes in adolescent smoking progression. Method: Data are from an ongoing prospective study of the long-term outcome of early risk factors studied since birth. At age 15 years, 220 participants (108 males, 112 females) completed a self-report questionnaire measuring smoking behavior and were genotyped for five dopamine gene variants. Results: Smoking initiation was related to allelic variation in the dopamine D-4 receptor gene (DRD4), whereas smoking continuation and dependence showed association with the dopamine D-2 receptor gene (DRD2). Adolescents with the seven-repeat allele of the common DRD4 exon 3 polymorphism had rates of ever smoking that were significantly higher than in those with other genotypes. Once smoking started, carriers of the T allele of a single nucleotide polymorphism of DRD2 (rs4648317) reported higher rates of current smoking and scored higher on nicotine dependence than their allelic counterparts. Among current smokers, intention to quit was significantly lower in adolescents homozygous for the 10-repeat allele of the common dopamine transporter 3 untranslated region polymorphism. Conclusions: Our results provide preliminary evidence of genetic influences on different stages of smoking and suggest the importance of specific dopamine genes in smoking progression in adolescence.}, language = {en} } @misc{TarasovaMerzKissetal.2019, author = {Tarasova, Larisa and Merz, Ralf and Kiss, Andrea and Basso, Stefano and Bl{\"o}chl, G{\"u}nter and Merz, Bruno and Viglione, Alberto and Pl{\"o}tner, Stefan and Guse, Bj{\"o}rn and Schumann, Andreas and Fischer, Svenja and Ahrens, Bodo and Anwar, Faizan and B{\´a}rdossy, Andr{\´a}s and B{\"u}hler, Philipp and Haberlandt, Uwe and Kreibich, Heidi and Krug, Amelie and Lun, David and M{\"u}ller-Thomy, Hannes and Pidoto, Ross and Primo, Cristina and Seidel, Jochen and Vorogushyn, Sergiy and Wietzke, Luzie}, title = {Causative classification of river flood events}, series = {Wiley Interdisciplinary Reviews : Water}, volume = {6}, journal = {Wiley Interdisciplinary Reviews : Water}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {2049-1948}, doi = {10.1002/wat2.1353}, pages = {23}, year = {2019}, abstract = {A wide variety of processes controls the time of occurrence, duration, extent, and severity of river floods. Classifying flood events by their causative processes may assist in enhancing the accuracy of local and regional flood frequency estimates and support the detection and interpretation of any changes in flood occurrence and magnitudes. This paper provides a critical review of existing causative classifications of instrumental and preinstrumental series of flood events, discusses their validity and applications, and identifies opportunities for moving toward more comprehensive approaches. So far no unified definition of causative mechanisms of flood events exists. Existing frameworks for classification of instrumental and preinstrumental series of flood events adopt different perspectives: hydroclimatic (large-scale circulation patterns and atmospheric state at the time of the event), hydrological (catchment scale precipitation patterns and antecedent catchment state), and hydrograph-based (indirectly considering generating mechanisms through their effects on hydrograph characteristics). All of these approaches intend to capture the flood generating mechanisms and are useful for characterizing the flood processes at various spatial and temporal scales. However, uncertainty analyses with respect to indicators, classification methods, and data to assess the robustness of the classification are rarely performed which limits the transferability across different geographic regions. It is argued that more rigorous testing is needed. There are opportunities for extending classification methods to include indicators of space-time dynamics of rainfall, antecedent wetness, and routing effects, which will make the classification schemes even more useful for understanding and estimating floods. This article is categorized under: Science of Water > Water Extremes Science of Water > Hydrological Processes Science of Water > Methods}, 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} } @article{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 = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging}, volume = {6}, journal = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging}, number = {3}, publisher = {Elsevier Science}, address = {Amsterdam}, issn = {0006-3223}, doi = {10.1016/j.bpsc.2020.08.017}, pages = {259 -- 269}, 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{KaminskiSchlagenhaufRappetal.2018, author = {Kaminski, Jakob A. and Schlagenhauf, Florian and Rapp, Michael Armin 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{KaminskiSchlagenhaufRappetal.2018, author = {Kaminski, Jakob and Schlagenhauf, Florian and Rapp, Michael Armin and Awasthi, Swapnil and Ruggeri, Barbara and Deserno, Lorenz and Laura, Daedelow and Banaschewski, Tobias and Bokde, Arun and Quinlan, Erin Burke and Buechel, Christian and Bromberg, Uli 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 and Froehner, Juliane and Walter, Henrik and Whelan, Robert and Ripke, Stephan and Schumann, Gunter and Heinz, Andreas}, title = {Variance in Dopaminergic Markers}, series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, volume = {83}, journal = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, number = {9}, publisher = {Elsevier}, address = {New York}, organization = {IMAGEN Consortium}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2018.02.311}, pages = {S118 -- S118}, year = {2018}, language = {en} } @misc{AwasthiKaminskiRappetal.2019, author = {Awasthi, Swapnil and Kaminski, Jakob and Rapp, Michael Armin and Schlagenhauf, Florian and Walter, Henrik and Ruggeri, Barbara and Ripke, Stephan and Schumann, Gunter and Heinz, Andreas}, title = {A neural signature of malleability}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {29}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2017.08.139}, pages = {S858 -- S859}, year = {2019}, abstract = {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.}, language = {en} } @article{ClarkeLauchtRidingeretal.2011, author = {Clarke, Toni-Kim and Laucht, Manfred and Ridinger, Monika and Wodarz, Norbert and Rietschel, Marcella and Maier, Wolfgang and Lathrop, Mark and Lourdusamy, Anbarasu and Zimmermann, Ulrich S. and Desrivieres, Sylvane and Schumann, Gunter}, title = {KCNJ6 is associated with adult alcohol dependence and involved in gene x early life stress interactions in adolescent alcohol drinking}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {36}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {6}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2010.247}, pages = {1142 -- 1148}, year = {2011}, abstract = {Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p = 0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p = 0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.}, language = {en} } @article{KaminskiSchlagenhaufRappetal.2018, author = {Kaminski, Jakob A. and Schlagenhauf, Florian and Rapp, Michael Armin 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} }