@article{ZohselBuchmannBlomeyeretal.2014, author = {Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Hohm, Erika and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Mothers' prenatal stress and their children's antisocial outcomes - a moderating role for the dopamine receptor D4 (DRD4) gene}, series = {The journal of child psychology and psychiatry}, volume = {55}, journal = {The journal of child psychology and psychiatry}, number = {1}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0021-9630}, doi = {10.1111/jcpp.12138}, pages = {69 -- 76}, year = {2014}, abstract = {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.}, language = {en} } @article{WittBuchmannBlomeyeretal.2011, author = {Witt, Stephanie H. and Buchmann, Arlette F. and Blomeyer, Dorothea and Nieratschker, Vanessa and Treutlein, Jens and Esser, G{\"u}nter and Schmidt, Martin H. and Bidlingmaier, Martin and Wiedemann, Klaus and Rietschel, Marcella and Laucht, Manfred and Wuest, Stefan and Zimmermann, Ulrich S.}, title = {An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses}, series = {Psychoneuroendocrinology}, volume = {36}, journal = {Psychoneuroendocrinology}, number = {7}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2010.12.015}, pages = {1010 -- 1020}, year = {2011}, abstract = {Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.}, language = {en} } @article{SchmidHohmBlomeyeretal.2007, author = {Schmid, Brigitte and Hohm, Erika and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Laucht, Manfred}, title = {Concurrent alcohol and tobacco use during early adolescence characterizes a group at risk}, issn = {0735-0414}, doi = {10.1093/alcalc/agm024}, year = {2007}, abstract = {Aims: To investigate whether concurrent alcohol and tobacco use during early adolescence characterizes a subgroup that differs from users of one substance only regarding several risk factors for later substance use problems. Methods: Participants were from a prospective longitudinal cohort study of 384 children at risk for later psychopathology, with the majority being born with obstetric complications and psychosocial adversities. Assessments of adolescent drug consumption and related intrapersonal characteristics were obtained at age 15. Results: Compared to consumers of alcohol only, 15-year-olds drinking and smoking during the same time period (past 4 weeks) had significantly higher levels of consumption and more excessive use of alcohol, started drinking at an earlier age, had higher scores on the Fagerstrom Test for Nicotine Dependence, and more cannabis use. This group could be distinguished from users of alcohol only by higher novelty seeking and more positive alcohol effect expectancies. Compared to consumers of tobacco only, concurrent users reported higher nicotine dependence and more cannabis use. No significant differences were observed regarding frequency and age at initiation of tobacco use, tobacco-related sensitivity, self- efficacy and instrumentality as well as novelty seeking. Conclusions: Concurrent alcohol and tobacco use during early adolescence is associated with characteristics that are well known as risk factors for later alcohol use problems and dependence and that should be targeted by prevention programs.}, language = {en} } @article{SchmidBuchmannTrautmannVillalbaetal.2013, author = {Schmid, Brigitte and Buchmann, Arlette F. and Trautmann-Villalba, Patricia and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Maternal stimulation in infancy predicts hypothalamic-pituitary-adrenal axis reactivity in young men}, series = {Journal of neural transmission}, volume = {120}, journal = {Journal of neural transmission}, number = {8}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-013-0970-8}, pages = {1247 -- 1257}, year = {2013}, abstract = {Evidence from animal research has demonstrated the effect of early maternal care on the offspring's endocrine and behavioral stress response in adulthood. The present prospective study investigates, in humans, the long-term impact of maternal responsiveness and stimulation during early mother-child interaction on adrenocorticotropic hormone (ACTH) and cortisol response to a psychosocial laboratory stressor in adulthood. The data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a 10-min standardized nursing and playing situation and evaluated by trained raters for maternal stimulation and infant and maternal responsiveness. At age 19 years, 270 participants (146 females, 124 males) completed the Trier Social Stress Test. The results indicated that less maternal stimulation during early interaction at age 3 months predicted diminished plasma ACTH and cortisol increase in response to acute psychosocial stress in male, but not female offspring. In contrast, maternal responsiveness was found to be unrelated to hypothalamic-pituitary-adrenal (HPA) reactivity. In accordance with the findings from animal research, the present study provides prospective evidence in humans of a long-term association between early maternal interaction behavior and the offspring's hormonal stress response in young adulthood, suggesting that poor maternal stimulation in early infancy may result in reduced HPA axis reactivity to an acute psychosocial stressor in males.}, language = {en} } @article{SchmidBlomeyerBuchmannetal.2011, author = {Schmid, Brigitte and Blomeyer, Dorothea and Buchmann, Arlette F. and Trautmann-Villalba, Patricia and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Quality of early mother-child interaction associated with depressive psychopathology in the offspring - a prospective study from infancy to adulthood}, series = {Journal of psychiatric research}, volume = {45}, journal = {Journal of psychiatric research}, number = {10}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2011.05.010}, pages = {1387 -- 1394}, year = {2011}, abstract = {Evidence from animal research has revealed that less maternal care results in disturbed emotionality in the offspring. In the present study, the long-term impact of maternal responsiveness and stimulation during early mother child interaction on depressive psychopathology was examined until adulthood. Data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness and stimulation as well as infant responsiveness were evaluated by trained raters. At age 19 years, 314 participants (145 males, 169 females) were characterized on measures of depression through interview and questionnaire. In addition, measures of depression and anxiety were available from assessments in childhood. Results indicated that less maternal stimulation during early interaction was associated with a higher risk of depression in the offspring until the age of 19 years. In addition, children of less stimulating mothers showed more depressive symptoms at age 19 years and displayed more anxiety and depressive symptoms between the ages of 4.5 and 15 years. In contrast, maternal responsiveness was unrelated to children's outcome. In accordance with findings from animal research, the present study provides first longitudinal evidence in humans of a continuous and long-term influence of early maternal interaction behavior on the offspring's psychological adjustment until adulthood. The results suggest that the amount of maternally initiated contact behavior in a very early developmental stage may be crucial for children's mental health, regardless of child and maternal responsiveness.}, language = {en} } @article{SchmidBlomeyerBeckeretal.2009, author = {Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Treutlein, Jens and Zimmermann, Ulrich S. and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Rietschel, Marcella and Laucht, Manfred}, title = {The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-olds}, issn = {1355-6215}, doi = {10.1111/j.1369-1600.2009.00171.x}, year = {2009}, abstract = {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.}, language = {en} } @article{PoustkaZohselBlomeyeretal.2015, author = {Poustka, Luise and Zohsel, Katrin and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmid, Brigitte and Trautmann-Villalba, Patricia and Hohmann, Sarah and Becker, Katja and Esser, G{\"u}nter and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis}, series = {Journal of psychiatric research}, volume = {70}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.psychires.2015.08.018}, pages = {83 -- 90}, year = {2015}, abstract = {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.}, language = {en} } @article{NikitopoulosZohselBlomeyeretal.2014, author = {Nikitopoulos, Joerg and Zohsel, Katrin and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Jennen-Steinmetz, Christine and Becker, Katja and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence}, series = {Journal of psychiatric research}, volume = {59}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2014.08.012}, pages = {53 -- 59}, year = {2014}, language = {en} } @article{LauchtTreutleinSchmidetal.2009, author = {Laucht, Manfred and Treutlein, Jens and Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Impact of psychosocial adversity on alcohol intake in young adults : moderation by the LL genotype of the serotonin transporter polymorphism}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2009.02.010}, year = {2009}, abstract = {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.}, language = {en} } @article{LauchtTreutleinBlomeyeretal.2013, author = {Laucht, Manfred and Treutlein, Jens and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Banaschewski, Tobias}, title = {Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults findings from a longitudinal study}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {23}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {5}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2012.06.002}, pages = {358 -- 367}, year = {2013}, abstract = {Accumulating research suggests a moderating role for the corticotropin-releasing hormone receptor 1 gene (CRHR1) in the association between childhood adversity and adult depression. The present study aims to replicate recent findings using different genetic variants and measures of early adversity assessed both prospectively and retrospectively. Data were collected in the context of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. 300 participants (137 males, 163 females) were genotyped for four CRHR1 SNPs (rs7209436, rs110402, rs242924, and rs17689882) and completed the Beck Depression Inventory at ages 19, 22 and 23 years. Childhood adversity was assessed using the Childhood Trauma Questionnaire and by a standardized parent interview yielding an index of family adversity. Our results indicate that CRHR1 and childhood adversity interacted to predict depressive symptoms in young adults. Specifically, we found that the impact of childhood maltreatment on adult depressive symptoms was significantly higher in individuals (i) with two copies of the CRHR1 TAT haplotype, and (ii) homozygous for the G allele of rs17689882. The interaction was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report, but not to prospectively ascertain objective family adversity. The present study partially replicates recent findings of a CRHR1 by childhood adversity interaction with regard to adult depression highlighting the subjective characteristics of the environmental pathogen that is operative in this interaction.}, language = {en} }