TY - JOUR A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Schmid, Brigitte A1 - Jennen-Steinmetz, Christine A1 - Schmidt, Martin H. A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Age at first drink moderates the impact of current stressful life events on drinking behavior in young adults JF - Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism N2 - Background: Recent evidence from animal experiments and studies in humans suggests that early age at first drink (AFD) may lead to higher stress-induced drinking. The present study aimed to extend these findings by examining whether AFD interacted with stressful life events (SLE) and/or with daily hassles regarding the impact on drinking patterns among young adults. Method: In 306 participants of an epidemiological cohort study, AFD was assessed together with SLE during the past 3 years, daily hassles in the last month, and drinking behavior at age 22. As outcome variables, 2 variables were derived, reflecting different aspects of alcohol use: the amount of alcohol consumed in the last month and the drinking frequency, indicated by the number of drinking days in the last month. Results: Linear regression models revealed an interaction effect between the continuous measures of AFD and SLE on the amount of alcohol consumed. The earlier young adults had their first alcoholic drink and the higher the levels of SLE they were exposed to, the disproportionately more alcohol they consumed. Drinking frequency was not affected by an interaction of these variables, while daily hassles and their interaction with AFD were unrelated to drinking behavior. Conclusions: These findings highlight the importance of early age at drinking onset as a risk factor for later heavy drinking under high load of SLE. Prevention programs should aim to raise age at first contact with alcohol. Additionally, support in stressful life situations and the acquisition of effective coping strategies might prevent heavy drinking in those with earlier drinking onset. KW - Age at First Drink KW - Drinking Behavior KW - Longitudinal Study KW - Stressful Life Events KW - Daily Hassles Y1 - 2011 U6 - https://doi.org/10.1111/j.1530-0277.2011.01447.x SN - 0145-6008 VL - 35 IS - 6 SP - 1142 EP - 1148 PB - Wiley-Blackwell CY - Malden ER - TY - JOUR A1 - Heinrich, Angela A1 - Buchmann, Arlette F. A1 - Zohsel, Katrin A1 - Dukal, Helene A1 - Frank, Josef A1 - Treutlein, Jens A1 - Nieratschker, Vanessa A1 - Witt, Stephanie H. A1 - Brandeis, Daniel A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Laucht, Manfred A1 - Rietschel, Marcella T1 - Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence JF - Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man N2 - Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk. The externalizing disorders group had significantly lower NR3C1 methylation levels than the lifetime depressive disorder group (p = 0.009) and healthy controls (p = 0.001) This report of lower methylation levels in NR3C1 in externalizing disorders may indicate a mechanism through which the differential development of externalizing disorders as opposed to depressive disorders might occur. KW - Epigenetic KW - Glucocorticoid receptor KW - Methylation KW - Externalizing disorders KW - Adolescents Y1 - 2015 U6 - https://doi.org/10.1007/s10519-015-9721-y SN - 0001-8244 SN - 1573-3297 VL - 45 IS - 5 SP - 529 EP - 536 PB - Springer CY - New York ER - TY - JOUR A1 - Witt, Stephanie H. A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Nieratschker, Vanessa A1 - Treutlein, Jens A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Bidlingmaier, Martin A1 - Wiedemann, Klaus A1 - Rietschel, Marcella A1 - Laucht, Manfred A1 - Wuest, Stefan A1 - Zimmermann, Ulrich S. T1 - An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses JF - Psychoneuroendocrinology N2 - 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. KW - GxE interaction KW - Stress KW - HPA KW - Neuropeptide Y KW - Early adversity Y1 - 2011 U6 - https://doi.org/10.1016/j.psyneuen.2010.12.015 SN - 0306-4530 VL - 36 IS - 7 SP - 1010 EP - 1020 PB - Elsevier CY - Oxford 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 - 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 - 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 - Buchmann, Arlette F. A1 - Hellweg, Rainer A1 - Rietschel, Marcella A1 - Treutlein, Jens A1 - Witt, Stephanie H. A1 - Zimmermann, Ulrich S. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Laucht, Manfred A1 - Deuschle, Michael T1 - BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms - a prospective study JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val(66)Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val(66)Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val(66)Met and 5-HTTLPR genotype. KW - BDNF KW - 5-HTTLPR KW - Human KW - Early psychosocial adversity KW - Longitudinal study KW - Depression Y1 - 2013 U6 - https://doi.org/10.1016/j.euroneuro.2012.09.003 SN - 0924-977X VL - 23 IS - 8 SP - 902 EP - 909 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Laucht, Manfred A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Treutlein, Jens A1 - Shmidt, Martin H. A1 - Esser, Günter A1 - Jennen-Steinmetz, Christine A1 - Rietschel, Marcella A1 - Zimmermann, Ulrich S. A1 - Banaschewski, Tobias T1 - Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis Y1 - 2012 ER - TY - JOUR A1 - Laucht, Manfred A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Treutlein, Jens A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Jennen-Steinmetz, Christine A1 - Rietschel, Marcella A1 - Zimmermann, Ulrich S. A1 - Banaschewski, Tobias T1 - Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis JF - The journal of child psychology and psychiatry N2 - 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. KW - Catechol-O-methyltransferase gene KW - alcohol use KW - adolescents KW - parenting KW - gene-environment interaction Y1 - 2012 U6 - https://doi.org/10.1111/j.1469-7610.2011.02408.x SN - 0021-9630 VL - 53 IS - 4 SP - 351 EP - 359 PB - Wiley-Blackwell CY - Malden ER - TY - JOUR A1 - Buchmann, Arlette F. A1 - Laucht, Manfred A1 - Schmid, Brigitte A1 - Wiedemann, Klaus A1 - Mann, Karl F. A1 - Zimmermann, Ulrich S. T1 - Cigarette craving increases after a psychosocial stress test and is related to cortisol stress response but not to dependence scores in daily smokers N2 - Stress is known to induce cigarette craving in smokers, but the underlying mechanisms are widely unknown. We investigated how dependence severity, smoking habits and stress-induced cortisol secretion are associated with increased cigarette craving after a standardised laboratory stressor. Hundred and six healthy participants (50 men, age 18-19 years) underwent a standardised public speaking stress task. In all, 35 smoked daily (DS), 13 smoked occasionally (OS), and 58 never smoked (NS). Smoking was unrestricted until 2 h before stress onset. Plasma cortisol was measured before and up to 95 min after the stressor. All current smokers rated intensity of cigarette craving immediately before and immediately after the stressor using the Brief Questionnaire of Smoking Urges (BQSU). Cortisol levels significantly increased in response to stress in all groups. The magnitude of this stress response was significantly lower in DS compared with OS and NS but did not differ between OS and NS. Baseline BQSU scores were significantly higher in DS than OS. BQSU scores increased significantly during the stress period and were positively correlated to the cortisol response in the DS but were unrelated to their nicotine dependence scores. In OS, no change in cigarette craving could be observed. In daily smokers, cigarette craving is increased after compared with before stress exposure and is related to the magnitude of cortisol stress response rather than to severity of nicotine dependence. This result supports, but does not prove, the concept that hypothalamus-pituitary-adrenal stimulation is one of the mechanisms how stress can elicit cigarette craving. Y1 - 2010 UR - http://jop.sagepub.com/ U6 - https://doi.org/10.1177/0269881108095716 SN - 0269-8811 ER - TY - JOUR A1 - Buchmann, Arlette F. A1 - Schmid, Brigitte A1 - Blomeyer, Dorothea A1 - Zimmermann, Ulrich S. A1 - Jennen-Steinmetz, Christine A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Mann, Karl F. A1 - Laucht, Manfred T1 - Drinking against unpleasant emotions : possible outcome of early onset of alcohol use? N2 - 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. Y1 - 2010 UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1530-0277 U6 - https://doi.org/10.1111/j.1530-0277.2010.01180.x SN - 0145-6008 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 - 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 - TY - JOUR A1 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Baumeister, Sarah A1 - Hohm, Erika A1 - Zohsel, Katrin A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Hohmann, Sarah A1 - Wolf, Isabella A1 - Plichta, Michael M. A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Effect of prenatal exposure to tobacco smoke on inhibitory control neuroimaging results from a 25-Year prospective study JF - JAMA psychiatry N2 - IMPORTANCE: There is accumulating evidence relating maternal smoking during pregnancy to attention-deficit/hyperactivity disorder (ADHD) without elucidating specific mechanisms. Research investigating the neurobiological underpinnings of this disorder has implicated deficits during response inhibition. Attempts to uncover the effect of prenatal exposure to nicotine on inhibitory control may thus be of high clinical importance. MAIN OUTCOMES AND MEASURES: Functional magnetic resonance imaging response, morphometric data, lifetime ADHD symptoms, and novelty seeking. RESULTS: Participants prenatally exposed to nicotine exhibited a weaker response in the anterior cingulate cortex (t(168) = 4.46; peak Montreal Neurological Institute [MNI] coordinates x = -2, y = 20, z = 30; familywise error [FWE]-corrected P = .003), the right inferior frontal gyrus (t(168) = 3.65; peak MNI coordinates x = 44, y = 38, z = 12; FWE-corrected P = .04), the left inferior frontal gyrus (t(168) = 4.09; peak MNI coordinates x = -38, y = 36, z = 8; FWE-corrected P = .009), and the supramarginal gyrus (t(168) = 5.03; peak MNI coordinates x = 64, y = -28, z = 22; FWE-corrected P = .02) during the processing of the NoGo compared to neutral stimuli, while presenting a decreased volume in the right inferior frontal gyrus. These findings were obtained irrespective of the adjustment of confounders, ADHD symptoms, and novelty seeking. There was an inverse relationship between inferior frontal gyrus activity and ADHD symptoms and between anterior cingulate cortex activity and novelty seeking. CONCLUSIONS AND RELEVANCE: These findings point to a functional involvement of prenatal exposure to tobacco smoke in neural alterations similar to ADHD, which underlines the importance of smoking prevention treatments. Y1 - 2014 U6 - https://doi.org/10.1001/jamapsychiatry.2014.786 SN - 2168-622X SN - 2168-6238 VL - 71 IS - 7 SP - 786 EP - 796 PB - American Veterinary Medical Association CY - Chicago ER - TY - JOUR A1 - Holz, Nathalie A1 - Boecker-Schlier, Regina A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Baumeister, Sarah A1 - Hohmann, Sarah A1 - Jennen-Steinmetz, Christine A1 - Wolf, Isabella A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Plichta, Michael M. A1 - Meyer-Lindenberg, Andreas A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression JF - Cerebral cortex N2 - Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOAx CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders. KW - aggression KW - amygdala KW - fMRI KW - life stress KW - MAOA Y1 - 2016 U6 - https://doi.org/10.1093/cercor/bhu249 SN - 1047-3211 SN - 1460-2199 VL - 26 SP - 904 EP - 914 PB - Oxford Univ. Press CY - Cary ER - 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 - GEN A1 - Boecker-Schlier, Regina A1 - Holz, Nathalie E. A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Plichta, Michael M. A1 - Wolf, Isabella A1 - Baumeister, Sarah A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years T2 - PLoS one Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0112155 SN - 1932-6203 VL - 9 IS - 10 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Boecker-Schlier, Regina A1 - Holz, Nathalie E. A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Plichta, Michael M. A1 - Wolf, Isabella A1 - Baumeister, Sarah A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years JF - PLoS one N2 - Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0104185 SN - 1932-6203 VL - 9 IS - 8 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Buchmann, Arlette F. A1 - Kopf, Daniel A1 - Westphal, Sabine A1 - Lederbogen, Florian A1 - Banaschewski, Tobias A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Zimmermann, Ulrich S. A1 - Laucht, Manfred A1 - Deuschle, Michael T1 - Impact of early parental child-rearing behavior on young adults' cardiometabolic risk profile : a prospective study N2 - Objective: To examine prospectively whether early parental child-rearing behavior is a predictor of cardiometabolic outcome in young adulthood when other potential risk factors are controlled. Metabolic factors associated with increased risk for cardiovascular disease have been found to vary, depending on lifestyle as well as genetic predisposition. Moreover, there is evidence suggesting that environmental conditions, such as stress in pre- and postnatal life, may have a sustained impact on an individual's metabolic risk profile. Methods: Participants were drawn from a prospective, epidemiological, cohort study followed up from birth into young adulthood. Parent interviews and behavioral observations at the age of 3 months were conducted to assess child-rearing practices and mother-infant interaction in the home setting and in the laboratory. In 279 participants, anthropometric characteristics, low-density lipoprotein and high-density lipoprotein cholesterol, apolipoproteins, and triglycerides were recorded at age 19 years. In addition, structured interviews were administered to the young adults to assess indicators of current lifestyle and education. Results: Adverse early-life interaction experiences were significantly associated with lower levels of high- density lipoprotein cholesterol and apolipoprotein A1 in young adulthood. Current lifestyle variables and level of education did not account for this effect, although habitual smoking and alcohol consumption also contributed significantly to cardiometabolic outcomes. Conclusions: These findings suggest that early parental child-rearing behavior may predict health outcome in later life through its impact on metabolic parameters in adulthood. Y1 - 2010 UR - http://www.psychosomaticmedicine.org/ U6 - https://doi.org/10.1097/Psy.0b013e3181c88343 SN - 0033-3174 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 -