TY - JOUR A1 - Buchmann, Arlette F. A1 - Schmid, Brigitte A1 - Blomeyer, Dorothea A1 - Becker, Katja A1 - Treutlein, Jens A1 - Zimmermann, Ulrich S. A1 - Jennen-Steinmetz, Christine A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Rietschel, Marcella A1 - Schumann, Gunter A1 - Laucht, Manfred T1 - Impact of age at first drink on vulnerability to alcohol-related problems : testing the marker hypothesis in a prospective study of young adults N2 - 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. Y1 - 2009 UR - http://www.sciencedirect.com/science/journal/00223956 U6 - https://doi.org/10.1016/j.jpsychires.2009.02.006 SN - 0022-3956 ER - TY - JOUR A1 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Baumeister, Sarah A1 - Plichta, Michael M. A1 - Cattrell, Anna A1 - Schumann, Gunter A1 - Esser, Günter A1 - Schmidt, Martin A1 - Buitelaar, Jan A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder JF - Frontiers in human neuroscience N2 - Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. KW - childhood adversity KW - conduct disorder KW - amygdala KW - ventral striatum KW - fMRI Y1 - 2016 U6 - https://doi.org/10.1093/scan/nsw120 SN - 1749-5016 SN - 1749-5024 VL - 12 IS - 2 SP - 261 EP - 272 PB - Oxford Univ. Press CY - Oxford ER - 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 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Jennen-Steinmetz, Christine A1 - Hohm, Erika A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Baumeister, Sarah A1 - Plichta, Michael M. A1 - Esser, Günter A1 - Schmidt, Martin A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Early maternal care may counteract familial liability for psychopathology in the reward circuitry JF - Social Cognitive and Affective Neuroscience N2 - Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants’ previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development. KW - maternal care KW - ADHD KW - ventral striatum KW - fMRI KW - resilience KW - aggression Y1 - 2018 U6 - https://doi.org/10.1093/scan/nsy087 SN - 1749-5016 SN - 1749-5024 VL - 13 IS - 11 SP - 1191 EP - 1201 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Boecker-Schlier, Regina A1 - Holz, Nathalie E. A1 - Hohm, Erika A1 - Zohsel, Katrin A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Baumeister, Sarah A1 - Wolf, Isabella A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Association between pubertal stage at first drink and neural reward processing in early adulthood JF - Addiction biology N2 - Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention. KW - alcohol-related problems KW - electroencephalography KW - functional magnetic resonance imaging KW - puberty KW - reward processing Y1 - 2017 U6 - https://doi.org/10.1111/adb.12413 SN - 1355-6215 SN - 1369-1600 VL - 22 SP - 1402 EP - 1415 PB - Wiley CY - Hoboken 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 - 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 - Holtmann, Martin A1 - Buchmann, Arlette F. A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - The child behavior checklist-dysregulation profile predicts substance use, suicidality, and functional impairment : a longitudinal analysis N2 - Recent studies have identified a Child Behavior Checklist profile that characterizes children with severe affective and behavioral dysregulation (CBCL-dysregulation profile, CBCL-DP). In two recent longitudinal studies the CBCL-DP in childhood was associated with heightened rates of comorbid psychiatric disorders, among them bipolar disorder, an increased risk for suicidality, and marked psychosocial impairment at young-adult follow-up. This is the first study outside the US that examines the longitudinal course of the CBCL-DP. Methods: We studied the diagnostic and functional trajectories and the predictive utility of the CBCL-DP in the Mannheim Study of Children at Risk, an epidemiological cohort study on the outcome of early risk factors from birth into adulthood. A total of 325 young adults (151 males, 174 females) participated in the 19-year assessment. Results: Young adults with a higher CBCL-DP score in childhood were at increased risk for substance use disorders, suicidality and poorer overall functioning at age 19, even after adjustment for parental education, family income, impairment and psychiatric disorders at baseline. Childhood dysregulation was not related to bipolar disorder in young adulthood. The CBCL-DP was neither a precursor of a specific pattern of comorbidity nor of comorbidity in general. Conclusions: Children with high CBCL-DP values are at risk for later severe, psychiatric symptomatology. The different developmental trajectories suggest that the CBCL-DP is not simply an early manifestation of a single disease process but might rather be an early developmental risk marker of a persisting deficit of self-regulation of affect and behavior. Y1 - 2011 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 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Early smoking onset may promise initial pleasurable sensations and later addiction JF - Addiction biology N2 - There is converging evidence suggesting a particular susceptibility to the addictive properties of nicotine among adolescents. The aim of the current study was to prospectively ascertain the relationship between age at first cigarette and initial smoking experiences, and to examine the combined effects of these characteristics of adolescent smoking behavior on adult smoking. It was hypothesized that the association between earlier age at first cigarette and later development of nicotine dependence may, at least in part, be attributable to differences in experiencing pleasurable early smoking sensations. Data were drawn from the participants of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. Structured interviews at age 15, 19 and 22 years were conducted to assess the age at first cigarette, early smoking experiences and current smoking behavior in 213 young adults. In addition, the participants completed the Fagerstrom Test for Nicotine Dependence. Adolescents who smoked their first cigarette at an earlier age reported more pleasurable sensations from the cigarette, and they were more likely to be regular smokers at age 22. The age at first cigarette also predicted the number of cigarettes smoked and dependence at age 22. Thus, both the age of first cigarette and the pleasure experienced from the cigarette independently predicted aspects of smoking at age 22. KW - Adolescence KW - age at first cigarette KW - dependence KW - early smoking experiences KW - longitudinal study KW - pleasurable smoking sensations Y1 - 2013 U6 - https://doi.org/10.1111/j.1369-1600.2011.00377.x SN - 1369-1600 VL - 18 IS - 6 SP - 947 EP - 954 PB - Wiley-Blackwell CY - Hoboken ER -