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 - 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 - 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 - CHAP A1 - Laucht, Manfred A1 - Blomeyer, Dorothea A1 - El-Faddagh, Mahha A1 - Esser, Günter A1 - Schmidt, Martin A1 - Banaschewski, Tobias A1 - Becker, Katja T1 - Are regulatory problems in infancy precursors of ADHD in childhood? a moderating role for the dopamine D4 receptor gene T2 - Infant mental health journal Y1 - 2011 SN - 0163-9641 VL - 32 IS - 3 SP - 212 EP - 212 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Laucht, Manfred A1 - Becker, Katja A1 - Frank, Josef A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Treutlein, Jens A1 - Skowronek, Markus H. A1 - Schumann, Gunter T1 - Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence N2 - 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. Y1 - 2008 U6 - https://doi.org/10.1097/Chi.0b013e31816bff77 SN - 0890-8567 ER - TY - JOUR A1 - Becker, Katja A1 - Blomeyer, Dorothea A1 - El-Faddagh, Mahha A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - From regulatory problems in infancy to attention-deficit/hyperactivity disorder in childhood : a moderating role for the dopamine D4 receptor gene? N2 - To examine whether the dopamine receptor D4 gene (DRD4) exon III VNTR moderates the risk of infants with regulatory disorders for developing attention-deficit/hyperactivity disorder (ADHD) later in childhood. In a prospective longitudinal study of children at risk for later psychopathology, 300 participants were assessed for regulatory problems in infancy, DRD4 genotype, and ADHD symptoms and diagnoses from childhood to adolescence. To examine a potential moderating effect on ADHD measures, linear and logistic regressions were computed. Models were fit for the main effects of the DRD4 genotype (presence or absence of the 7r allele) and regulatory problems (presence or absence), with the addition of the interaction term. All models were controlled for sex, family adversity, and obstetric risk status. In children without the DRD4-7r allele, a history of regulatory problems in infancy was unrelated to later ADHD. But in children with regulatory problems in infancy, the additional presence of the DRD4-7r allele increased the risk for ADHD in childhood. The DRD4 genotype seems to moderate the association between regulatory problems in infancy and later ADHD. A replication study is needed before further conclusions can be drawn, however. Y1 - 2010 UR - http://www.sciencedirect.com/science/journal/00223476 U6 - https://doi.org/10.1016/j.jpeds.2009.12.005 SN - 0022-3476 ER - TY - JOUR A1 - Schmid, Brigitte A1 - Blomeyer, Dorothea A1 - Becker, Katja A1 - Treutlein, Jens A1 - Zimmermann, Ulrich S. A1 - Buchmann, Arlette F. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Rietschel, Marcella A1 - Laucht, Manfred T1 - The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-olds N2 - Recent evidence suggests that heterogeneity in the age at onset could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to examine interactions between two DAT1 polymorphisms and different initiation ages with regard to alcohol and tobacco consumption levels and dependence. Two hundred and ninety-one young adults (135 males, 156 females) participating in the Mannheim Study of Children at Risk were genotyped for the 40-bp variable number of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was assessed at age 15 and 19 years. Information about current alcohol and tobacco consumption was obtained at age 19 years using self-report measures and structured interviews. Results suggest that age at onset of intensive consumption moderated the association of the DAT1 gene with early adult substance use and dependence, revealing a DAT1 effect only among individuals homozygous for the 10r allele of the 40-bp VNTR who had started daily smoking or being intoxicated early in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting an early age at first intoxication showed higher current alcohol consumption at age 19 years. In contrast, no interaction between rs27072 and the age at first cigarette with regard to later smoking was observed. These findings provide evidence that the DAT1 gene interacts with an early heavy or regular drug exposure of the maturing adolescent brain to predict substance (ab)use in young adulthood. Further studies are required to confirm these findings. Y1 - 2009 UR - http://www3.interscience.wiley.com/cgi-bin/issn?DESCRIPTOR=PRINTISSN&VALUE=1355-6215 U6 - https://doi.org/10.1111/j.1369-1600.2009.00171.x SN - 1355-6215 ER - TY - JOUR A1 - Laucht, Manfred A1 - Treutlein, Jens A1 - Schmid, Brigitte A1 - Blomeyer, Dorothea A1 - Becker, Katja A1 - Buchmann, Arlette F. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Jennen-Steinmetz, Christine A1 - Rietschel, Marcella A1 - Zimmermann, Ulrich S. A1 - Banaschewski, Tobias T1 - Impact of psychosocial adversity on alcohol intake in young adults : moderation by the LL genotype of the serotonin transporter polymorphism N2 - Background: Evidence from animal studies supports a role for serotonin transporter gene promoter polymorphism (5-HTTLPR) gene-environment interaction (G X E) in the development of excessive alcohol intake. Few studies in humans have been conducted on this topic, yielding inconsistent results. The present study aims to further explore G x E between 5-HTTLPR and exposure to psychosocial adversity on alcohol consumption in a high-risk community sample of young adults. Methods: Data were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study following the outcome of early risk factors from birth into young adulthood. At age 19 years, 309 participants (142 male participants, 167 female participants) were genotyped for the biallelic and triallelic 5-HTTLPR and were administered a 45-day alcohol timeline follow-back interview, providing measures of the total number of drinks and the number of binge drinking days. Psychosocial adversity was assessed at birth (family adversity) and at age 19 (negative life events). Results: In contrast to various previous reports, a significant G x E emerged, indicating that, when exposed to high psychosocial adversity, individuals with the LL genotype of 5-HTTLPR exhibited more hazardous drinking than those carrying the S allele or those without exposure to adversity. This effect, which was confined to male participants, held both for different classifications of 5-HTTLPR and different types of adversity. Conclusions: One explanation for the discrepant results might be heterogeneity in alcohol phenotypes. While the L allele relates more strongly to early-onset alcoholism, the S allele may be linked more closely to alcohol use associated with anxiety and depression. Y1 - 2009 UR - http://www.sciencedirect.com/science/journal/00063223 U6 - https://doi.org/10.1016/j.biopsych.2009.02.010 SN - 0006-3223 ER - TY - JOUR A1 - Laucht, Manfred A1 - Treutlein, Jens A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Schmid, Brigitte A1 - Becker, Katja A1 - Zimmermann, Ulrich S. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Rietschel, Marcella A1 - Banaschewski, Tobias T1 - Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology : evidence from a high-risk community sample of young adults N2 - Previous research examining gene-environment interaction (G x E) with regard to vulnerability to depression and anxiety has yielded conflicting results. The present study was designed to further investigate G x F between 5-HTTLPR and exposure to environmental adversity, using different phenotypic and genotypic characterizations as well as different types of adversity within a prospective study design. Data were available from an ongoing epidemiological cohort Study following the outcome of early risk factors from birth to adulthood. At age 19 yr, 309 participants (142 males, 167 females) were characterized on measures of depression and anxiety through interview and questionnaire (DSM-IV diagnosis, Beck Depression Inventory, Harm Avoidance). Environmental adversity was assessed at birth (family adversity), and at age 19 yr (stressful life events). Bi- and tri-allelic 5-HTTLPR genotypes were obtained from genomic DNA. Results indicated that depression and anxiety in 19-yr-olds were strongly associated with both family adversity and stressful life events. Individuals with the LL genotype of 5-HTTLPR who were exposed to high family adversity displayed significantly higher rates of depressive or anxiety disorders and had more depressive symptoms than those without either condition. This G x E replicates recent findings from an epidemiological cohort study of adolescents but is in contrast to many previous reports suggesting an interaction with the S allele. No evidence for G x E was obtained with regard to current stressful life events and trait anxiety. One possible source for the conflicting findings might be attributed to heterogeneity in depression phenotypes and environmental adversity. Y1 - 2009 UR - http://journals.cambridge.org/jid_PNP U6 - https://doi.org/10.1017/S1461145708009875 SN - 1461-1457 ER - TY - JOUR A1 - Hohmann, Sarah A1 - Becker, Katja A1 - Fellinger, Johannes A1 - Banaschewski, Tobias A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Laucht, Manfred T1 - Evidence for epistasis between the 5-HTTLPR and the dopamine D4 receptor polymorphisms in externalizing behavior among 15-year-olds N2 - The present study aimed to clarify the functional role of genes in the dopamine and serotonin systems by examining whether polymorphisms in these genes are related to adolescent externalizing behavior either alone or in interaction with each other. Participants were selected from an ongoing prospective study of the outcome of early risk factors. At age 15 years, 298 adolescents (144 males, 154 females) completed the Youth Self Report, 296 primary caregivers the Child Behavior Checklist and 253 teachers the Teacher Report Form. DNA was genotyped for the DRD4 exon III VNTR and the 5-HTTLPR polymorphisms. Results revealed that individuals with the DRD4 7r allele reported significantly more externalizing behavior than carriers of other variants. In addition, a significant interaction emerged, indicating that adolescents carrying two copies of the 5-HTTLPR short allele and the DRD4 7r variant scored highest on aggressive and/or delinquent behavior compared to other genotypes. This result suggests an effect of 5-HTTLPR on externalizing behavior in the presence of DRD4 7r but no effect in its absence. Y1 - 2009 UR - http://www.springerlink.com/content/101493 U6 - https://doi.org/10.1007/s00702-009-0290-1 SN - 0300-9564 ER -