TY - JOUR A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Lascorz, Jesus A1 - Zimmermann, Ulrich S. A1 - Esser, Günter A1 - Desrivieres, Sylvane A1 - Schmidt, Martin H. A1 - Banaschewski, Tobias A1 - Schumann, Gunter A1 - Laucht, Manfred T1 - Association of PER2 genotype and stressful life events with alcohol drinking in young adults JF - PLoS one N2 - 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. Y1 - 2013 U6 - https://doi.org/10.1371/journal.pone.0059136 SN - 1932-6203 VL - 8 IS - 3 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Clarke, Toni-Kim A1 - Laucht, Manfred A1 - Ridinger, Monika A1 - Wodarz, Norbert A1 - Rietschel, Marcella A1 - Maier, Wolfgang A1 - Lathrop, Mark A1 - Lourdusamy, Anbarasu A1 - Zimmermann, Ulrich S. A1 - Desrivieres, Sylvane A1 - Schumann, Gunter T1 - KCNJ6 is associated with adult alcohol dependence and involved in gene x early life stress interactions in adolescent alcohol drinking JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology N2 - 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. KW - alcoholism KW - genetics KW - GIRK2 KW - stress KW - gene x environment KW - KCNJ6 Y1 - 2011 U6 - https://doi.org/10.1038/npp.2010.247 SN - 0893-133X VL - 36 IS - 6 SP - 1142 EP - 1148 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Xie, Chao A1 - Jia, Tianye A1 - Rolls, Edmund T. A1 - Robbins, Trevor W. A1 - Sahakian, Barbara J. A1 - Zhang, Jie A1 - Liu, Zhaowen A1 - Cheng, Wei A1 - Luo, Qiang A1 - Zac Lo, Chun-Yi A1 - Schumann, Gunter A1 - Feng, Jianfeng A1 - Wang, He A1 - Banaschewski, Tobias A1 - Barker, Gareth J. A1 - Bokde, Arun L.W. A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivières, Sylvane A1 - Flor, Herta A1 - Grigis, Antoine A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Heinz, Andreas A1 - Hohmann, Sarah 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 - Fröhner, Juliane H. A1 - Smolka, Michael N. A1 - Walter, Henrik A1 - Whelan, Robert T1 - Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 860 KW - adolescents KW - depression KW - monetary incentive delay task KW - nonreward sensitivity KW - orbitofrontal cortex KW - reward anticipation KW - reward sensitivity KW - ventral striatum Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-557882 SN - 1866-8364 IS - 3 ER - TY - JOUR A1 - Xie, Chao A1 - Jia, Tianye A1 - Rolls, Edmund T. A1 - Robbins, Trevor W. A1 - Sahakian, Barbara J. A1 - Zhang, Jie A1 - Liu, Zhaowen A1 - Cheng, Wei A1 - Luo, Qiang A1 - Zac Lo, Chun-Yi A1 - Schumann, Gunter A1 - Feng, Jianfeng A1 - Wang, He A1 - Banaschewski, Tobias A1 - Barker, Gareth J. A1 - Bokde, Arun L.W. A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivières, Sylvane A1 - Flor, Herta A1 - Grigis, Antoine A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Heinz, Andreas A1 - Hohmann, Sarah 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 - Fröhner, Juliane H. A1 - Smolka, Michael N. A1 - Walter, Henrik A1 - Whelan, Robert T1 - Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging N2 - 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. KW - adolescents KW - depression KW - monetary incentive delay task KW - nonreward sensitivity KW - orbitofrontal cortex KW - reward anticipation KW - reward sensitivity KW - ventral striatum Y1 - 2021 U6 - https://doi.org/10.1016/j.bpsc.2020.08.017 SN - 2451-9022 SN - 2451-9030 VL - 6 IS - 3 SP - 259 EP - 269 PB - Elsevier Science CY - Amsterdam ER -