@article{LauchtTreutleinBlomeyeretal.2009, author = {Laucht, Manfred and Treutlein, Jens and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Becker, Katja and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Rietschel, Marcella and Banaschewski, Tobias}, title = {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}, issn = {1461-1457}, doi = {10.1017/S1461145708009875}, year = {2009}, abstract = {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.}, 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{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{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{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{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{BuchmannSchmidBlomeyeretal.2010, author = {Buchmann, Arlette F. and Schmid, Brigitte and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Mann, Karl F. and Laucht, Manfred}, title = {Drinking against unpleasant emotions : possible outcome of early onset of alcohol use?}, issn = {0145-6008}, doi = {10.1111/j.1530-0277.2010.01180.x}, year = {2010}, abstract = {Background: Recent animal and human studies indicate that the exposure to alcohol during early adolescence increases the risk for heavy alcohol use in response to stress. The purpose of this study was to examine whether this effect may be the consequence of a higher susceptibility to develop "drinking to cope" motives among early initiators. Methods: Data from 320 participants were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study. Structured interviews at age 15 and 19 were used to assess age at first alcohol experience and drunkenness. The young adults completed questionnaires to obtain information about the occurrence of stressful life events during the past 4 years and current drinking habits. In addition, alcohol use under conditions of negative states was assessed with the Inventory of Drinking Situations. Results: The probability of young adults' alcohol use in situations characterized by unpleasant emotions was significantly increased the earlier they had initiated the use of alcohol, even when controlling for current drinking habits and stressful life events. Similar results were obtained for the age at first drunkenness. Conclusions: The findings strengthen the hypothesis that alcohol experiences during early adolescence facilitate drinking to regulate negative affect as an adverse coping strategy which may represent the starting point of a vicious circle comprising drinking to relieve stress and increased stress as a consequence of drinking.}, 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} } @misc{LauchtBlomeyerBuchmannetal.2012, author = {Laucht, Manfred and Blomeyer, Dorothea and Buchmann, Arlette F. and Treutlein, Jens and Shmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis}, year = {2012}, language = {en} } @article{LauchtBlomeyerBuchmannetal.2012, author = {Laucht, Manfred and Blomeyer, Dorothea and Buchmann, Arlette F. and Treutlein, Jens and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis}, series = {The journal of child psychology and psychiatry}, volume = {53}, journal = {The journal of child psychology and psychiatry}, number = {4}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0021-9630}, doi = {10.1111/j.1469-7610.2011.02408.x}, pages = {351 -- 359}, year = {2012}, abstract = {Background: Recently, first evidence has been reported for a geneparenting interaction (G x E) with regard to adolescent alcohol use. The present investigation set out to extend this research using the catechol-O-methyltransferase (COMT) Val158Met polymorphism as a genetic susceptibility factor. Moreover, the current study examined whether a potential G x E would be consistent with one of two models of geneenvironment interplay (genetic vulnerability vs. differential susceptibility). Methods: Data were collected as part of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. Two hundred and eighty-five participants (130 males, 155 females) were genotyped for the COMT Val(158) Met polymorphism and were administered an alcohol interview, providing measures of current frequency and amount of drinking at ages 15 and 19 years. Information on three dimensions of perceived parenting behavior was obtained from the 15-year-olds. Results: Adolescents homozygous for the Met allele showed higher drinking activity at age 19 years when their parents had engaged in less supervision or were less involved, while their drinking activity was reduced under conditions of favorable parenting. No such relationship was found in individuals carrying the Val allele. Conclusions: The present findings correspond with the pattern of results predicted by the differential susceptibility hypothesis, suggesting that environmental variation would have a greater impact in individuals carrying a genetic susceptibility such that, in this group, exposure to negative environmental conditions would result in more adverse outcomes and the experience of favorable conditions would lead to more positive outcomes.}, language = {en} }