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 - 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 - 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 JF - The journal of child psychology and psychiatry N2 - Background: 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. KW - Dysregulation KW - childhood KW - comorbidity KW - longitudinal KW - irritability KW - depression KW - ADHD KW - substance use KW - suicidality KW - CBCL KW - bipolar Y1 - 2011 U6 - https://doi.org/10.1111/j.1469-7610.2010.02309.x SN - 0021-9630 VL - 52 IS - 2 SP - 139 EP - 147 PB - Wiley-Blackwell CY - Malden 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 - 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 - 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 - 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 - Schmid, Brigitte A1 - Buchmann, Arlette F. A1 - Trautmann-Villalba, Patricia A1 - Blomeyer, Dorothea A1 - Zimmermann, Ulrich S. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Maternal stimulation in infancy predicts hypothalamic-pituitary-adrenal axis reactivity in young men JF - Journal of neural transmission N2 - 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. KW - ACTH KW - Cortisol KW - HPA axis KW - Mother-infant interaction Y1 - 2013 U6 - https://doi.org/10.1007/s00702-013-0970-8 SN - 0300-9564 VL - 120 IS - 8 SP - 1247 EP - 1257 PB - Springer CY - Wien 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 - JOUR A1 - Laucht, Manfred A1 - Treutlein, Jens A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Schmidt, Martin A1 - Esser, Günter A1 - Jennen-Steinmetz, Christine A1 - Reitschelb, Marcel A1 - Banaschewski, Tobias T1 - Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults: Findings from a longitudinal study Y1 - 2012 ER - TY - JOUR A1 - Laucht, Manfred A1 - Treutlein, Jens A1 - Blomeyer, Dorothea A1 - Buchmann, Arlette F. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Jennen-Steinmetz, Christine A1 - Rietschel, Marcella A1 - Banaschewski, Tobias T1 - Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults findings from a longitudinal study JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - 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. KW - Corticotropin-releasing hormone receptor 1 gene KW - Depression KW - Maltreatment KW - Family adversity KW - Young adults KW - Gene-environment interaction Y1 - 2013 U6 - https://doi.org/10.1016/j.euroneuro.2012.06.002 SN - 0924-977X VL - 23 IS - 5 SP - 358 EP - 367 PB - Elsevier CY - Amsterdam ER - 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 - 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 - 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 - 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 - Buchmann, Arlette F. A1 - Holz, Nathalie A1 - Boecker-Schlier, Regina A1 - Blomeyer, Dorothea A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Zimmermann, Ulrich S. A1 - Laucht, Manfred T1 - Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license. KW - FKBP5 KW - Stress KW - HPA KW - Cortisol KW - Childhood adversity Y1 - 2014 U6 - https://doi.org/10.1016/j.euroneuro.2013.12.001 SN - 0924-977X SN - 1873-7862 VL - 24 IS - 6 SP - 837 EP - 845 PB - Elsevier CY - Amsterdam ER -