TY - JOUR A1 - Buchmann, Arlette F. A1 - Zohsel, Katrin A1 - Blomeyer, Dorothea A1 - Hohm, Erika A1 - Hohmann, Sarah A1 - Jennen-Steinmetz, Christine A1 - Treutlein, Jens A1 - Becker, Katja A1 - Banaschewski, Tobias A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Brandeis, Daniel A1 - Poustka, Luise A1 - Zimmermann, Ulrich S. A1 - Laucht, Manfred T1 - Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults JF - Psychopharmacology N2 - Considerable evidence suggests that genetic factors combine with environmental influences to impact on the development of aggressive behavior. A genetic variant that has repeatedly been reported to render individuals more sensitive to the presence of adverse experiences, including stress exposure during fetal life, is the seven-repeat allele of the dopamine D4 receptor (DRD4) gene. The present investigation concentrated on the interplay of prenatal maternal stress and DRD4 genotype in predicting self-reported aggression in young adults. As disruption of the hypothalamic-pituitary-adrenal system has been discussed as a pathophysiological pathway to aggression, cortisol stress reactivity was additionally examined. As part of an epidemiological cohort study, prenatal maternal stress was assessed by maternal interview 3 months after childbirth. Between the ages of 19 and 23 years, 298 offspring (140 males, 158 females) completed the Young Adult Self-Report to measure aggressive behavior and were genotyped for the DRD4 gene. At 19 years, 219 participants additionally underwent the Trier Social Stress Test to determine cortisol reactivity. Extending earlier findings with respect to childhood antisocial behavior, the results revealed that, under conditions of higher prenatal maternal stress, carriers of the DRD4 seven-repeat allele displayed more aggression in adulthood (p = 0.032). Moreover, the same conditions which seemed to promote aggression were found to predict attenuated cortisol secretion (p = 0.028). This is the first study to indicate a long-term impact of prenatal stress exposure on the cortisol stress response depending on DRD4 genotype. KW - Prenatal stress KW - Aggression KW - Cortisol KW - DRD4 KW - Gene-environment interaction Y1 - 2014 U6 - https://doi.org/10.1007/s00213-014-3484-7 SN - 0033-3158 SN - 1432-2072 VL - 231 IS - 16 SP - 3089 EP - 3097 PB - Springer CY - New York ER - TY - JOUR A1 - McLoughlin, Grainne A1 - Palmer, Jason A1 - Makeig, Scott A1 - Bigdely-Shamlo, Nima A1 - Banaschewski, Tobias A1 - Laucht, Manfred A1 - Brandeis, D. T1 - EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes JF - Brain Topography N2 - Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness. KW - EEG KW - Genetics KW - DRD4 KW - COMT KW - ICA KW - Measure projection Y1 - 2017 U6 - https://doi.org/10.1007/s10548-017-0601-z SN - 0896-0267 SN - 1573-6792 VL - 31 IS - 3 SP - 392 EP - 406 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Nikitopoulos, Joerg A1 - Zohsel, Katrin A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Schmid, Brigitte A1 - Jennen-Steinmetz, Christine A1 - Becker, Katja A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Brandeis, Daniel A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence JF - Journal of psychiatric research KW - DRD4 KW - Early maternal care KW - Externalizing behavior KW - Adolescence KW - Gene-environment interaction Y1 - 2014 U6 - https://doi.org/10.1016/j.jpsychires.2014.08.012 SN - 0022-3956 SN - 1879-1379 VL - 59 SP - 53 EP - 59 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Poustka, Luise A1 - Zohsel, Katrin A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Schmid, Brigitte A1 - Trautmann-Villalba, Patricia A1 - Hohmann, Sarah A1 - Becker, Katja A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Brandeis, Daniel A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis JF - Journal of psychiatric research N2 - Recent longitudinal studies have indicated that affective and behavioral dysregulation in childhood is associated with an increased risk for various negative outcomes in later life. However, few studies to date have examined early mechanisms preceding dysregulation during early childhood. Aim of this study was to elucidate early mechanisms relating to dysregulation in later life using data from an epidemiological cohort study on the long-term outcome of early risk factors from birth to adulthood. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness was evaluated by trained raters. Infant regulatory problems were assessed on the basis of a parent interview and direct observation by trained raters. At age 8 and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist (CBCL). Additionally, participants were genotyped for the dopamine D4 receptor (DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between maternal responsiveness, DRD4 genotype and infant regulatory problems was detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the DRD4 7r allele with regulatory problems at age 3 months showed significantly more behavior problems associated with the CBCL-DP during childhood when exposed to less maternal responsiveness. In contrast, no effect of maternal responsiveness was observed in DRD4 7r carriers without infant regulatory problems and in non-carriers of the DRD4 7r allele. This prospective longitudinal study extends earlier findings regarding the association of the CBCL-DP with early parenting and later psychopathology, introducing both DRD4 genotype and infant regulatory problems as important moderators. (C) 2015 Elsevier Ltd. All rights reserved. KW - Dysregulation KW - Childhood KW - Infant regulatory problems KW - Parenting quality KW - DRD4 KW - Gene-environment interaction Y1 - 2015 U6 - https://doi.org/10.1016/j.psychires.2015.08.018 SN - 0022-3956 SN - 1879-1379 VL - 70 SP - 83 EP - 90 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Zohsel, Katrin A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Hohm, Erika A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Brandeis, Daniel A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Mothers' prenatal stress and their children's antisocial outcomes - a moderating role for the dopamine receptor D4 (DRD4) gene JF - The journal of child psychology and psychiatry N2 - ResultsUnder conditions of elevated prenatal maternal stress, children carrying one or two DRD4 7r alleles were at increased risk of a diagnosis of CD/ODD. Moreover, homozygous carriers of the DRD4 7r allele displayed more externalizing behavior following exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD4 4r allele turned out to be insensitive to the effects of prenatal stress. ConclusionsThis study is the first to report a gene-environment interaction related to DRD4 and prenatal maternal stress using data from a prospective study, which extends earlier findings on the impact of prenatal maternal stress with respect to childhood antisocial behavior. KW - Prenatal stress KW - antisocial KW - conduct disorder KW - DRD4 KW - gene-environment interaction Y1 - 2014 U6 - https://doi.org/10.1111/jcpp.12138 SN - 0021-9630 SN - 1469-7610 VL - 55 IS - 1 SP - 69 EP - 76 PB - Wiley-Blackwell CY - Hoboken ER -