@article{ZohselHolzHohmetal.2017, author = {Zohsel, Katrin and Holz, Nathalie E. and Hohm, Erika and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Fewer self-reported depressive symptoms in young adults exposed to maternal depressed mood during pregnancy}, series = {Journal of Affective Disorders}, volume = {209}, journal = {Journal of Affective Disorders}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0165-0327}, doi = {10.1016/j.jad.2016.08.059}, pages = {155 -- 162}, year = {2017}, abstract = {Background: Depressed mood is prevalent during pregnancy, with accumulating evidence suggesting an impact on developmental outcome in the offspring. However, the long-term effects of prenatal maternal depression regarding internalizing psychopathology in the offspring are as yet unclear. Results: In n=85 young adults exposed to prenatal maternal depressed mood, no significantly higher risk for a diagnosis of depressive disorder was observed. However, they reported significantly lower levels of depressive symptoms. This association was especially pronounced when prenatal maternal depressed mood was present during the first trimester of pregnancy and when maternal mood was depressed pre- as well as postnatally. At an uncorrected level only, prenatal maternal depressed mood was associated with decreased amygdala volume. Limitations: Prenatal maternal depressed mood was not assessed during pregnancy, but shortly after childbirth. No diagnoses of maternal clinical depression during pregnancy were available. Conclusions: Self-reported depressive symptoms do not imply increased, but rather decreased symptom levels in young adults who were exposed to prenatal maternal depressed mood. A long-term perspective may be important when considering consequences of prenatal risk factors.}, language = {en} } @article{ZohselHohmSchmidtetal.2017, author = {Zohsel, Katrin and Hohm, Erika and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Die langfristigen Auswirkungen von Fr{\"u}hgeburtlichkeit auf kognitive Entwicklung und Schulerfolg}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000235}, pages = {221 -- 229}, year = {2017}, abstract = {In einer prospektiven L{\"a}ngsschnittstudie wurde der Zusammenhang zwischen fr{\"u}her Responsivit{\"a}t der Mutter und kognitiver Entwicklung ihrer fr{\"u}h- bzw. reifgeborenen Kinder untersucht. Im Alter von drei Monaten wurde daf{\"u}r die Mutter-Kind-Interaktion mittels Verhaltensbeobachtung erfasst. Bei n=351 der teilnehmenden Kinder (101 fr{\"u}hgeboren) wurde die allgemeine Intelligenz (IQ) im Alter von 11 Jahren und bei n=313 (85 fr{\"u}hgeboren) zus{\"a}tzlich der h{\"o}chste erreichte Schulabschluss bis 25 Jahren erhoben. Fr{\"u}hgeborene wiesen mit 11 Jahren einen signifikant niedrigeren IQ als Reifgeborene auf, nachdem f{\"u}r m{\"o}gliche konfundierende Faktoren kontrolliert worden war. Nur bei Fr{\"u}h-, nicht aber bei Reifgeborenen zeigte sich ein signifikanter positiver Zusammenhang zwischen m{\"u}tterlicher Responsivit{\"a}t und IQ. F{\"u}r die Wahrscheinlichkeit einen h{\"o}heren Schulabschluss (mind. Fachabitur) zu erreichen, fand sich weder ein signifikanter Effekt von Fr{\"u}hgeburtlichkeit noch von m{\"u}tterlicher Responsivit{\"a}t.}, language = {de} } @article{ZohselHohmSchmidtetal.2017, author = {Zohsel, Katrin and Hohm, Erika and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Long-Term Consequences of Early Psychosocial Risks}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, number = {4}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000233}, pages = {203 -- 209}, year = {2017}, abstract = {In einer prospektiven L{\"a}ngsschnittstudie wurden Auswirkungen fr{\"u}her psychosozialer Risiken bis ins junge Erwachsenenalter untersucht und dabei die Rolle von affektiver und behavioraler Dysregulation im Kindesalter als vermittelndem Faktor {\"u}berpr{\"u}ft. Drei Monate nach der Geburt wurde das Vorliegen von 11 psychosozialen Belastungsfaktoren erfasst. Im Alter von 8 - 15 Jahren wurde dreimal das Child Behavior Checklist-Dysregulationsprofil (CBCL-DP) erhoben. Mit 25 Jahren wurde ein Strukturiertes Klinisches Interview durchgef{\"u}hrt und 309 der Teilnehmer f{\"u}llten den Young Adult Self-Report aus. Fr{\"u}he psychosoziale Risiken gingen mit einem erh{\"o}hten Risiko f{\"u}r das Vorliegen eines Substanzmissbrauchs im jungen Erwachsenenalter sowie mit erh{\"o}htem externalisierendem und internalisierendem Problemverhalten einher. Der Zusammenhang zwischen fr{\"u}hen psychosozialen Risiken und sp{\"a}terem externalisierendem bzw. internalisierendem Problemverhalten wurde durch das CBCL-DP vermittelt.}, language = {de} } @article{ZohselBuchmannBlomeyeretal.2014, author = {Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Hohm, Erika and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Mothers' prenatal stress and their children's antisocial outcomes - a moderating role for the dopamine receptor D4 (DRD4) gene}, series = {The journal of child psychology and psychiatry}, volume = {55}, journal = {The journal of child psychology and psychiatry}, number = {1}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0021-9630}, doi = {10.1111/jcpp.12138}, pages = {69 -- 76}, year = {2014}, abstract = {ResultsUnder conditions of elevated prenatal maternal stress, children carrying one or two DRD4 7r alleles were at increased risk of a diagnosis of CD/ODD. Moreover, homozygous carriers of the DRD4 7r allele displayed more externalizing behavior following exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD4 4r allele turned out to be insensitive to the effects of prenatal stress. ConclusionsThis study is the first to report a gene-environment interaction related to DRD4 and prenatal maternal stress using data from a prospective study, which extends earlier findings on the impact of prenatal maternal stress with respect to childhood antisocial behavior.}, language = {en} } @article{ZohselBaldusSchmidtetal.2016, author = {Zohsel, Katrin and Baldus, Christiane and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Thomasius, Rainer and Laucht, Manfred}, title = {Predicting later problematic cannabis use from psychopathological symptoms during childhood and adolescence: Results of a 25-year longitudinal study}, series = {Drug and alcohol dependence : an international journal on biomedical and psychosocial approaches}, volume = {163}, journal = {Drug and alcohol dependence : an international journal on biomedical and psychosocial approaches}, publisher = {Elsevier}, address = {Clare}, issn = {0376-8716}, doi = {10.1016/j.drugalcdep.2016.04.012}, pages = {251 -- 255}, year = {2016}, abstract = {Background: Cannabis is the most commonly used illegal substance among adolescents and young adults. Problematic cannabis use is often associated with comorbid psychopathological problems. The purpose of the current study was to elucidate the underlying developmental processes connecting externalizing and internalizing psychopathology in childhood and adolescence with problematic cannabis use in young adulthood. Methods: Data were drawn from the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. For n = 307 participants, symptom scores of conduct/oppositional defiant disorder, attention problems, hyperactivity/impulsivity, and internalizing disorders were available for the periods of childhood (4.5-11 years) and adolescence (15 years). At age 25 years, problematic cannabis use was assessed via clinical interview and a self-rating questionnaire. Results: At age 25 years, problematic cannabis use was identified in n = 28 participants (9.1\%). Childhood conduct/oppositional behavior problems were predictive of problematic cannabis use during young adulthood when comorbid symptoms were controlled for. No such effect was found for childhood attention, hyperactivity/impulsivity or internalizing problems. With respect to psychopathological symptoms during adolescence, only attention problems were significantly related to later problematic cannabis use when controlling for comorbidity. Conclusions: The current study highlights the role of conduct/oppositional behavior problems during childhood and attention problems during adolescence in later problematic cannabis use. It sheds more light on the developmental sequence of childhood and adolescence psychopathology and young adult cannabis use, which is a prerequisite for effective prevention approaches. (C) 2016 Elsevier Ireland Ltd. All rights reserved.}, language = {en} } @misc{XieJiaRollsetal.2021, author = {Xie, Chao and Jia, Tianye and Rolls, Edmund T. and Robbins, Trevor W. and Sahakian, Barbara J. and Zhang, Jie and Liu, Zhaowen and Cheng, Wei and Luo, Qiang and Zac Lo, Chun-Yi and Schumann, Gunter and Feng, Jianfeng and Wang, He and Banaschewski, Tobias and Barker, Gareth J. and Bokde, Arun L.W. and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivi{\`e}res, Sylvane and Flor, Herta and Grigis, Antoine and Garavan, Hugh and Gowland, Penny and Heinz, Andreas and Hohmann, Sarah and Ittermann, Bernd and Martinot, Jean-Luc and Paill{\`e}re Martinot, Marie-Laure and Nees, Frauke and Papadopoulos Orfanos, Dimitri and Paus, Tom{\´a}š and Poustka, Luise and Fr{\"o}hner, Juliane H. and Smolka, Michael N. and Walter, Henrik and Whelan, Robert}, title = {Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {3}, issn = {1866-8364}, doi = {10.25932/publishup-55788}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-557882}, pages = {13}, year = {2021}, abstract = {BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.}, language = {en} } @article{XieJiaRollsetal.2021, author = {Xie, Chao and Jia, Tianye and Rolls, Edmund T. and Robbins, Trevor W. and Sahakian, Barbara J. and Zhang, Jie and Liu, Zhaowen and Cheng, Wei and Luo, Qiang and Zac Lo, Chun-Yi and Schumann, Gunter and Feng, Jianfeng and Wang, He and Banaschewski, Tobias and Barker, Gareth J. and Bokde, Arun L.W. and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivi{\`e}res, Sylvane and Flor, Herta and Grigis, Antoine and Garavan, Hugh and Gowland, Penny and Heinz, Andreas and Hohmann, Sarah and Ittermann, Bernd and Martinot, Jean-Luc and Paill{\`e}re Martinot, Marie-Laure and Nees, Frauke and Papadopoulos Orfanos, Dimitri and Paus, Tom{\´a}š and Poustka, Luise and Fr{\"o}hner, Juliane H. and Smolka, Michael N. and Walter, Henrik and Whelan, Robert}, title = {Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms}, series = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging}, volume = {6}, journal = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging}, number = {3}, publisher = {Elsevier Science}, address = {Amsterdam}, issn = {0006-3223}, doi = {10.1016/j.bpsc.2020.08.017}, pages = {259 -- 269}, year = {2021}, abstract = {BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.}, language = {en} } @article{SchmidBuchmannTrautmannVillalbaetal.2013, author = {Schmid, Brigitte and Buchmann, Arlette F. and Trautmann-Villalba, Patricia and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Maternal stimulation in infancy predicts hypothalamic-pituitary-adrenal axis reactivity in young men}, series = {Journal of neural transmission}, volume = {120}, journal = {Journal of neural transmission}, number = {8}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-013-0970-8}, pages = {1247 -- 1257}, year = {2013}, abstract = {Evidence from animal research has demonstrated the effect of early maternal care on the offspring's endocrine and behavioral stress response in adulthood. The present prospective study investigates, in humans, the long-term impact of maternal responsiveness and stimulation during early mother-child interaction on adrenocorticotropic hormone (ACTH) and cortisol response to a psychosocial laboratory stressor in adulthood. The data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a 10-min standardized nursing and playing situation and evaluated by trained raters for maternal stimulation and infant and maternal responsiveness. At age 19 years, 270 participants (146 females, 124 males) completed the Trier Social Stress Test. The results indicated that less maternal stimulation during early interaction at age 3 months predicted diminished plasma ACTH and cortisol increase in response to acute psychosocial stress in male, but not female offspring. In contrast, maternal responsiveness was found to be unrelated to hypothalamic-pituitary-adrenal (HPA) reactivity. In accordance with the findings from animal research, the present study provides prospective evidence in humans of a long-term association between early maternal interaction behavior and the offspring's hormonal stress response in young adulthood, suggesting that poor maternal stimulation in early infancy may result in reduced HPA axis reactivity to an acute psychosocial stressor in males.}, language = {en} } @article{SchmidBlomeyerBuchmannetal.2011, author = {Schmid, Brigitte and Blomeyer, Dorothea and Buchmann, Arlette F. and Trautmann-Villalba, Patricia and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Quality of early mother-child interaction associated with depressive psychopathology in the offspring - a prospective study from infancy to adulthood}, series = {Journal of psychiatric research}, volume = {45}, journal = {Journal of psychiatric research}, number = {10}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2011.05.010}, pages = {1387 -- 1394}, year = {2011}, abstract = {Evidence from animal research has revealed that less maternal care results in disturbed emotionality in the offspring. In the present study, the long-term impact of maternal responsiveness and stimulation during early mother child interaction on depressive psychopathology was examined until adulthood. Data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness and stimulation as well as infant responsiveness were evaluated by trained raters. At age 19 years, 314 participants (145 males, 169 females) were characterized on measures of depression through interview and questionnaire. In addition, measures of depression and anxiety were available from assessments in childhood. Results indicated that less maternal stimulation during early interaction was associated with a higher risk of depression in the offspring until the age of 19 years. In addition, children of less stimulating mothers showed more depressive symptoms at age 19 years and displayed more anxiety and depressive symptoms between the ages of 4.5 and 15 years. In contrast, maternal responsiveness was unrelated to children's outcome. In accordance with findings from animal research, the present study provides first longitudinal evidence in humans of a continuous and long-term influence of early maternal interaction behavior on the offspring's psychological adjustment until adulthood. The results suggest that the amount of maternally initiated contact behavior in a very early developmental stage may be crucial for children's mental health, regardless of child and maternal responsiveness.}, language = {en} } @article{SchmidBlomeyerBeckeretal.2009, author = {Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Treutlein, Jens and Zimmermann, Ulrich S. and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Rietschel, Marcella and Laucht, Manfred}, title = {The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-olds}, issn = {1355-6215}, doi = {10.1111/j.1369-1600.2009.00171.x}, year = {2009}, abstract = {Recent evidence suggests that heterogeneity in the age at onset could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to examine interactions between two DAT1 polymorphisms and different initiation ages with regard to alcohol and tobacco consumption levels and dependence. Two hundred and ninety-one young adults (135 males, 156 females) participating in the Mannheim Study of Children at Risk were genotyped for the 40-bp variable number of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was assessed at age 15 and 19 years. Information about current alcohol and tobacco consumption was obtained at age 19 years using self-report measures and structured interviews. Results suggest that age at onset of intensive consumption moderated the association of the DAT1 gene with early adult substance use and dependence, revealing a DAT1 effect only among individuals homozygous for the 10r allele of the 40-bp VNTR who had started daily smoking or being intoxicated early in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting an early age at first intoxication showed higher current alcohol consumption at age 19 years. In contrast, no interaction between rs27072 and the age at first cigarette with regard to later smoking was observed. These findings provide evidence that the DAT1 gene interacts with an early heavy or regular drug exposure of the maturing adolescent brain to predict substance (ab)use in young adulthood. Further studies are required to confirm these findings.}, language = {en} } @article{PoustkaZohselBlomeyeretal.2015, author = {Poustka, Luise and Zohsel, Katrin and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmid, Brigitte and Trautmann-Villalba, Patricia and Hohmann, Sarah and Becker, Katja and Esser, G{\"u}nter and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis}, series = {Journal of psychiatric research}, volume = {70}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.psychires.2015.08.018}, pages = {83 -- 90}, year = {2015}, abstract = {Recent longitudinal studies have indicated that affective and behavioral dysregulation in childhood is associated with an increased risk for various negative outcomes in later life. However, few studies to date have examined early mechanisms preceding dysregulation during early childhood. Aim of this study was to elucidate early mechanisms relating to dysregulation in later life using data from an epidemiological cohort study on the long-term outcome of early risk factors from birth to adulthood. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness was evaluated by trained raters. Infant regulatory problems were assessed on the basis of a parent interview and direct observation by trained raters. At age 8 and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist (CBCL). Additionally, participants were genotyped for the dopamine D4 receptor (DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between maternal responsiveness, DRD4 genotype and infant regulatory problems was detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the DRD4 7r allele with regulatory problems at age 3 months showed significantly more behavior problems associated with the CBCL-DP during childhood when exposed to less maternal responsiveness. In contrast, no effect of maternal responsiveness was observed in DRD4 7r carriers without infant regulatory problems and in non-carriers of the DRD4 7r allele. This prospective longitudinal study extends earlier findings regarding the association of the CBCL-DP with early parenting and later psychopathology, introducing both DRD4 genotype and infant regulatory problems as important moderators. (C) 2015 Elsevier Ltd. All rights reserved.}, language = {en} } @article{PitzerEsserSchmidtetal.2017, author = {Pitzer, Martina and Esser, G{\"u}nter and Schmidt, Martin H. and Hohm, Erika and Banaschewski, Tobias and Laucht, Manfred}, title = {Child regulative temperament as a mediator of parenting in the development of depressive symptoms}, series = {Journal of neural transmission}, volume = {124}, journal = {Journal of neural transmission}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-017-1682-2}, pages = {631 -- 641}, year = {2017}, abstract = {Child temperament as well as parenting behaviors have been linked to adolescent depression. Beyond their main effects, the interplay between these factors is of interest. For example, in an interactive model, a differential susceptibility of temperamental variants to parenting has been suggested. However, so far, the differential susceptibility hypothesis has mostly been studied with a focus on externalizing disorders. On the other hand, parenting may shape the child's temperament and vice versa in a transactional process. In a prospective, longitudinal at-risk sample (163 boys, 176 girls), we assessed emotional (easy-difficult) and regulative (self-control) temperament at ages 4.5, and 8 years, respectively, as well as parenting quality at age 4.5 years using the HOME inventory. Hierarchical linear regression analysis was used to investigate the prediction of depressive symptoms at age 11, measured by the Child Depression Inventory, including interaction terms between the temperament variable and parenting. We additionally tested whether parenting was mediated by child temperament. As previously reported, both self-control and parenting were longitudinally associated with preadolescent depressive symptoms. There were no interactive effects between temperament and parenting. However, the effects of parenting were partly mediated by self-control. Our data do not support a differential susceptibility of temperamental variants in the development of preadolescent depression. However, our results are in line with the assumption that parenting may shape young children's temperament, with positive parenting in the early childhood fostering the development of regulative temperament.}, language = {en} } @article{PaslakisBuchmannWestphaletal.2014, author = {Paslakis, Georgios and Buchmann, Arlette F. and Westphal, Sabine and Banaschewski, Tobias and Hohm, Erika and Zimmermann, Ulrich S. and Laucht, Manfred and Deuschle, Michael}, title = {Intrauterine exposure to cigarette smoke is associated with increased ghrelin concentrations in adulthood}, series = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships}, volume = {99}, journal = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0028-3835}, doi = {10.1159/000363325}, pages = {123 -- 129}, year = {2014}, abstract = {Background: The appetite-stimulating hormone ghrelin is a fundamental regulator of human energy metabolism. A series of studies support the notion that long-term appetite and weight regulation may be already programmed in early life and it could be demonstrated that the intrauterine environment affects the ghrelin system of the offspring. Animal studies have also shown that intrauterine programming of orexigenic systems persists even until adolescence/adulthood. Methods: We hypothesized that plasma ghrelin concentrations in adulthood may be associated with the intrauterine exposure to cigarette smoke. We examined this hypothesis in a sample of 19-year-olds followed up since birth in the framework of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study of the long-term outcome of early risk factors. Results: As a main finding, we found that ghrelin plasma concentrations in young adults who had been exposed to cigarette smoke in utero were significantly higher than in those without prenatal smoke exposure. Moreover, individuals with intrauterine nicotine exposure showed a significantly higher prevalence of own smoking habits and lower educational status compared to those in the group without exposure. Conclusion: Smoking during pregnancy may be considered as an adverse intrauterine influence that may alter the endocrine-metabolic status of the offspring even until early adulthood.}, language = {en} } @article{NikitopoulosZohselBlomeyeretal.2014, author = {Nikitopoulos, Joerg and Zohsel, Katrin and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Jennen-Steinmetz, Christine and Becker, Katja and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence}, series = {Journal of psychiatric research}, volume = {59}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2014.08.012}, pages = {53 -- 59}, year = {2014}, language = {en} } @article{MillenetLauchtHohmetal.2018, author = {Millenet, Sabina and Laucht, Manfred and Hohm, Erika and Jennen-Steinmetz, Christine and Hohmann, Sarah and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Zohsel, Katrin}, title = {Sex-specific trajectories of ADHD symptoms from adolescence to young adulthood}, series = {European child and adolescent psychiatry : offical journal of the European Society for Child and Adolescent Psychiatry}, volume = {27}, journal = {European child and adolescent psychiatry : offical journal of the European Society for Child and Adolescent Psychiatry}, number = {8}, publisher = {Springer}, address = {New York}, issn = {1018-8827}, doi = {10.1007/s00787-018-1129-9}, pages = {1067 -- 1075}, year = {2018}, abstract = {Reports of current ADHD symptoms in adults with a childhood diagnosis of ADHD are often discrepant: While one subgroup reports a particularly high level of current ADHD symptoms, another reports—in contrast—a very low level. The reasons for this difference remain unclear. Although sex might play a moderating role, it has not yet been examined in this regard. In an epidemiological cohort study from birth to young adulthood, childhood ADHD diagnoses were assessed at the ages of 4.5, 8, and 11 years based on parent ratings. Sex-specific development of ADHD symptoms was analyzed from the age of 15 to 25 years via self-reported ADHD symptoms in participants with (n = 47) and without childhood ADHD (n = 289) using a random coefficient regression model. The congruence between parent reports and adolescents' self-ratings was examined, and the role of childhood ADHD diagnosis, childhood OCC/CD, and childhood internalizing disorder as possible sex-specific predictors of self-reported ADHD symptoms at age 25 years was investigated. With regard to self-reported ADHD symptoms, females with a childhood ADHD diagnosis reported significantly more ADHD symptoms compared to females without childhood ADHD and males with and without ADHD throughout adolescence and young adulthood. In contrast, males with childhood ADHD did not differ from control males either at age 15 or at age 25 years. Only in females did a childhood diagnosis of an externalizing disorder (ADHD and CD/ODD) predict self-reported ADHD symptoms by age 25 years. Our findings suggest that self-reports of young adults with a childhood diagnosis of ADHD are influenced by sex. Specifically, females with childhood ADHD report increased levels of ADHD symptoms upon reaching adulthood. To correctly evaluate symptoms and impairment in this subgroup, other, more objective, sources of information may be advisable, such as neurophysiological measures.}, language = {en} } @article{McLoughlinPalmerMakeigetal.2017, author = {McLoughlin, Grainne and Palmer, Jason and Makeig, Scott and Bigdely-Shamlo, Nima and Banaschewski, Tobias and Laucht, Manfred and Brandeis, D.}, title = {EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes}, series = {Brain Topography}, volume = {31}, journal = {Brain Topography}, number = {3}, publisher = {Springer}, address = {Dordrecht}, issn = {0896-0267}, doi = {10.1007/s10548-017-0601-z}, pages = {392 -- 406}, year = {2017}, abstract = {Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.}, language = {en} } @article{LauchtTreutleinSchmidetal.2009, author = {Laucht, Manfred and Treutlein, Jens and Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Impact of psychosocial adversity on alcohol intake in young adults : moderation by the LL genotype of the serotonin transporter polymorphism}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2009.02.010}, year = {2009}, abstract = {Background: Evidence from animal studies supports a role for serotonin transporter gene promoter polymorphism (5-HTTLPR) gene-environment interaction (G X E) in the development of excessive alcohol intake. Few studies in humans have been conducted on this topic, yielding inconsistent results. The present study aims to further explore G x E between 5-HTTLPR and exposure to psychosocial adversity on alcohol consumption in a high-risk community sample of young adults. Methods: Data were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study following the outcome of early risk factors from birth into young adulthood. At age 19 years, 309 participants (142 male participants, 167 female participants) were genotyped for the biallelic and triallelic 5-HTTLPR and were administered a 45-day alcohol timeline follow-back interview, providing measures of the total number of drinks and the number of binge drinking days. Psychosocial adversity was assessed at birth (family adversity) and at age 19 (negative life events). Results: In contrast to various previous reports, a significant G x E emerged, indicating that, when exposed to high psychosocial adversity, individuals with the LL genotype of 5-HTTLPR exhibited more hazardous drinking than those carrying the S allele or those without exposure to adversity. This effect, which was confined to male participants, held both for different classifications of 5-HTTLPR and different types of adversity. Conclusions: One explanation for the discrepant results might be heterogeneity in alcohol phenotypes. While the L allele relates more strongly to early-onset alcoholism, the S allele may be linked more closely to alcohol use associated with anxiety and depression.}, language = {en} } @article{LauchtTreutleinBlomeyeretal.2013, author = {Laucht, Manfred and Treutlein, Jens and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Banaschewski, Tobias}, title = {Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults findings from a longitudinal study}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {23}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {5}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2012.06.002}, pages = {358 -- 367}, year = {2013}, abstract = {Accumulating research suggests a moderating role for the corticotropin-releasing hormone receptor 1 gene (CRHR1) in the association between childhood adversity and adult depression. The present study aims to replicate recent findings using different genetic variants and measures of early adversity assessed both prospectively and retrospectively. Data were collected in the context of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. 300 participants (137 males, 163 females) were genotyped for four CRHR1 SNPs (rs7209436, rs110402, rs242924, and rs17689882) and completed the Beck Depression Inventory at ages 19, 22 and 23 years. Childhood adversity was assessed using the Childhood Trauma Questionnaire and by a standardized parent interview yielding an index of family adversity. Our results indicate that CRHR1 and childhood adversity interacted to predict depressive symptoms in young adults. Specifically, we found that the impact of childhood maltreatment on adult depressive symptoms was significantly higher in individuals (i) with two copies of the CRHR1 TAT haplotype, and (ii) homozygous for the G allele of rs17689882. The interaction was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report, but not to prospectively ascertain objective family adversity. The present study partially replicates recent findings of a CRHR1 by childhood adversity interaction with regard to adult depression highlighting the subjective characteristics of the environmental pathogen that is operative in this interaction.}, language = {en} } @article{LauchtTreutleinBlomeyeretal.2012, author = {Laucht, Manfred and Treutlein, Jens and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmidt, Martin and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Reitschelb, Marcel and Banaschewski, Tobias}, title = {Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults: Findings from a longitudinal study}, year = {2012}, language = {en} } @article{LauchtTreutleinBlomeyeretal.2009, author = {Laucht, Manfred and Treutlein, Jens and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Becker, Katja and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Rietschel, Marcella and Banaschewski, Tobias}, title = {Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology : evidence from a high-risk community sample of young adults}, issn = {1461-1457}, doi = {10.1017/S1461145708009875}, year = {2009}, abstract = {Previous research examining gene-environment interaction (G x E) with regard to vulnerability to depression and anxiety has yielded conflicting results. The present study was designed to further investigate G x F between 5-HTTLPR and exposure to environmental adversity, using different phenotypic and genotypic characterizations as well as different types of adversity within a prospective study design. Data were available from an ongoing epidemiological cohort Study following the outcome of early risk factors from birth to adulthood. At age 19 yr, 309 participants (142 males, 167 females) were characterized on measures of depression and anxiety through interview and questionnaire (DSM-IV diagnosis, Beck Depression Inventory, Harm Avoidance). Environmental adversity was assessed at birth (family adversity), and at age 19 yr (stressful life events). Bi- and tri-allelic 5-HTTLPR genotypes were obtained from genomic DNA. Results indicated that depression and anxiety in 19-yr-olds were strongly associated with both family adversity and stressful life events. Individuals with the LL genotype of 5-HTTLPR who were exposed to high family adversity displayed significantly higher rates of depressive or anxiety disorders and had more depressive symptoms than those without either condition. This G x E replicates recent findings from an epidemiological cohort study of adolescents but is in contrast to many previous reports suggesting an interaction with the S allele. No evidence for G x E was obtained with regard to current stressful life events and trait anxiety. One possible source for the conflicting findings might be attributed to heterogeneity in depression phenotypes and environmental adversity.}, language = {en} } @inproceedings{LauchtBlomeyerElFaddaghetal.2011, author = {Laucht, Manfred and Blomeyer, Dorothea and El-Faddagh, Mahha and Esser, G{\"u}nter and Schmidt, Martin and Banaschewski, Tobias and Becker, Katja}, title = {Are regulatory problems in infancy precursors of ADHD in childhood? a moderating role for the dopamine D4 receptor gene}, series = {Infant mental health journal}, volume = {32}, booktitle = {Infant mental health journal}, number = {3}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0163-9641}, pages = {212 -- 212}, year = {2011}, language = {en} } @misc{LauchtBlomeyerBuchmannetal.2012, author = {Laucht, Manfred and Blomeyer, Dorothea and Buchmann, Arlette F. and Treutlein, Jens and Shmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis}, year = {2012}, language = {en} } @article{LauchtBlomeyerBuchmannetal.2012, author = {Laucht, Manfred and Blomeyer, Dorothea and Buchmann, Arlette F. and Treutlein, Jens and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis}, series = {The journal of child psychology and psychiatry}, volume = {53}, journal = {The journal of child psychology and psychiatry}, number = {4}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0021-9630}, doi = {10.1111/j.1469-7610.2011.02408.x}, pages = {351 -- 359}, year = {2012}, abstract = {Background: Recently, first evidence has been reported for a geneparenting interaction (G x E) with regard to adolescent alcohol use. The present investigation set out to extend this research using the catechol-O-methyltransferase (COMT) Val158Met polymorphism as a genetic susceptibility factor. Moreover, the current study examined whether a potential G x E would be consistent with one of two models of geneenvironment interplay (genetic vulnerability vs. differential susceptibility). Methods: Data were collected as part of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. Two hundred and eighty-five participants (130 males, 155 females) were genotyped for the COMT Val(158) Met polymorphism and were administered an alcohol interview, providing measures of current frequency and amount of drinking at ages 15 and 19 years. Information on three dimensions of perceived parenting behavior was obtained from the 15-year-olds. Results: Adolescents homozygous for the Met allele showed higher drinking activity at age 19 years when their parents had engaged in less supervision or were less involved, while their drinking activity was reduced under conditions of favorable parenting. No such relationship was found in individuals carrying the Val allele. Conclusions: The present findings correspond with the pattern of results predicted by the differential susceptibility hypothesis, suggesting that environmental variation would have a greater impact in individuals carrying a genetic susceptibility such that, in this group, exposure to negative environmental conditions would result in more adverse outcomes and the experience of favorable conditions would lead to more positive outcomes.}, language = {en} } @article{HolzZohselLauchtetal.2016, author = {Holz, Nathalie E. and Zohsel, Katrin and Laucht, Manfred and Banaschewski, Tobias and Hohmann, Sarah and Brandeis, Daniel}, title = {Gene x environment interactions in conduct disorder}, series = {Neuroscience \& biobehavioral reviews : official journal of the International Behavioral Neuroscience Society}, volume = {91}, journal = {Neuroscience \& biobehavioral reviews : official journal of the International Behavioral Neuroscience Society}, publisher = {Elsevier}, address = {Oxford}, issn = {0149-7634}, doi = {10.1016/j.neubiorev.2016.08.017}, pages = {239 -- 258}, year = {2016}, abstract = {Conduct disorder (CD) causes high financial and social costs, not only in affected families but across society, with only moderately effective treatments so far. There is consensus that CD is likely caused by the convergence of many different factors, including genetic and adverse environmental factors. There is ample evidence of gene-environment interactions in the etiology of CD on a behavioral level regarding genetically sensitive designs and candidate gene-driven approaches, most prominently and consistently represented by MAOA. However, conclusive indications of causal GxE patterns are largely lacking. Inconsistent findings, lack of replication and methodological limitations remain a major challenge. Likewise, research addressing the identification of affected brain pathways which reflect plausible biological mechanisms underlying GxE is still very sparse. Future research will have to take multilevel approaches into account, which combine genetic, environmental, epigenetic, personality, neural and hormone perspectives. A better understanding of relevant GxE patterns in the etiology of CD might enable researchers to design customized treatment options (e.g. biofeedback interventions) for specific subgroups of patients.}, language = {en} } @article{HolzBuchmannBoeckerSchlieretal.2015, author = {Holz, Nathalie E. and Buchmann, Arlette F. and Boecker-Schlier, Regina and Blomeyer, Dorothea and Baumeister, Sarah and Wolf, Isabella and Rietschel, Marcella and Witt, Stephanie H. and Plichta, Michael M. and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume}, series = {Brain structure \& function}, volume = {220}, journal = {Brain structure \& function}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {1863-2653}, doi = {10.1007/s00429-014-0729-5}, pages = {1355 -- 1368}, year = {2015}, abstract = {Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.}, language = {en} } @article{HolzBoeckerSchlierJennenSteinmetzetal.2018, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Jennen-Steinmetz, Christine and Hohm, Erika and Buchmann, Arlette F. and Blomeyer, Dorothea and Baumeister, Sarah and Plichta, Michael M. and Esser, G{\"u}nter and Schmidt, Martin and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Early maternal care may counteract familial liability for psychopathology in the reward circuitry}, series = {Social Cognitive and Affective Neuroscience}, volume = {13}, journal = {Social Cognitive and Affective Neuroscience}, number = {11}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsy087}, pages = {1191 -- 1201}, year = {2018}, abstract = {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.}, language = {en} } @article{HolzBoeckerSchlierHohmetal.2015, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Hohm, Erika and Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Baumeister, Sarah and Hohmann, Sarah and Wolf, Isabella and Plichta, Michael M. and Esser, G{\"u}nter and Schmidt, Martin and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {The Long-Term Impact of Early Life Poverty on Orbitofrontal Cortex Volume in Adulthood: Results from a Prospective Study Over 25 Years}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {40}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {4}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2014.277}, pages = {996 -- 1004}, year = {2015}, abstract = {Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0 = non-exposed (N = 134), I = exposed (N = 33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.}, language = {en} } @article{HolzBoeckerSchlierBuchmannetal.2017, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Baumeister, Sarah and Plichta, Michael M. and Cattrell, Anna and Schumann, Gunter and Esser, G{\"u}nter and Schmidt, Martin and Buitelaar, Jan and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder}, series = {Frontiers in human neuroscience}, volume = {12}, journal = {Frontiers in human neuroscience}, number = {2}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsw120}, pages = {261 -- 272}, year = {2017}, abstract = {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.}, language = {en} } @article{HolzBoeckerSchlierBaumeisteretal.2014, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Baumeister, Sarah and Hohm, Erika and Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Hohmann, Sarah and Wolf, Isabella and Plichta, Michael M. and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Effect of prenatal exposure to tobacco smoke on inhibitory control neuroimaging results from a 25-Year prospective study}, series = {JAMA psychiatry}, volume = {71}, journal = {JAMA psychiatry}, number = {7}, publisher = {American Veterinary Medical Association}, address = {Chicago}, issn = {2168-622X}, doi = {10.1001/jamapsychiatry.2014.786}, pages = {786 -- 796}, year = {2014}, abstract = {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.}, language = {en} } @article{HolzBoeckerSchlierBuchmannetal.2016, author = {Holz, Nathalie and Boecker-Schlier, Regina and Buchmann, Arlette F. and Blomeyer, Dorothea and Baumeister, Sarah and Hohmann, Sarah and Jennen-Steinmetz, Christine and Wolf, Isabella and Rietschel, Marcella and Witt, Stephanie H. and Plichta, Michael M. and Meyer-Lindenberg, Andreas and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression}, series = {Cerebral cortex}, volume = {26}, journal = {Cerebral cortex}, publisher = {Oxford Univ. Press}, address = {Cary}, issn = {1047-3211}, doi = {10.1093/cercor/bhu249}, pages = {904 -- 914}, year = {2016}, abstract = {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.}, language = {en} } @article{HoltmannBuchmannEsseretal.2011, author = {Holtmann, Martin and Buchmann, Arlette F. and Esser, G{\"u}nter and Schmidt, Martin H. and Banaschewski, Tobias and Laucht, Manfred}, title = {The child behavior checklist-dysregulation profile predicts substance use, suicidality, and functional impairment : a longitudinal analysis}, year = {2011}, abstract = {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.}, language = {en} } @article{HoltmannBuchmannEsseretal.2011, author = {Holtmann, Martin and Buchmann, Arlette F. and Esser, G{\"u}nter and Schmidt, Martin H. and Banaschewski, Tobias and Laucht, Manfred}, title = {The child behavior checklist-dysregulation profile predicts substance use, suicidality, and functional impairment a longitudinal analysis}, series = {The journal of child psychology and psychiatry}, volume = {52}, journal = {The journal of child psychology and psychiatry}, number = {2}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0021-9630}, doi = {10.1111/j.1469-7610.2010.02309.x}, pages = {139 -- 147}, year = {2011}, abstract = {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.}, language = {en} } @article{HohmannZohselBuchmannetal.2016, author = {Hohmann, Sarah and Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Holz, Nathalie and Boecker-Schlier, Regina and Jennen-Steinmetz, Christine and Rietschel, Marcella and Witt, Stephanie H. and Schmidt, Martin H. and Esser, G{\"u}nter and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Hohm, Erika and Laucht, Manfred}, title = {Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood}, series = {Journal of neural transmission}, volume = {123}, journal = {Journal of neural transmission}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-016-1582-x}, pages = {885 -- 894}, year = {2016}, abstract = {Findings on the etiology of aggressive behavior have provided evidence for an effect both of genetic factors, such as variation in the monoamine oxidase A (MAOA) gene, and adverse environmental factors. Recent studies have supported the existence of gene × environment interactions, with early experiences playing a key role. In the present study, the effects of prenatal nicotine exposure, MAOA genotype and their interaction on aggressive behavior during young adulthood were examined. In a sample of 272 young adults (129 males, 143 females) from an epidemiological cohort study, smoking during pregnancy was measured with a standardized parent interview at the offspring's age of 3 months. Aggressive behavior was assessed between the ages of 19 and 25 years using the Young Adult Self-Report. DNA was genotyped for the MAOA 5\&\#8242; untranslated region variable number of tandem repeats polymorphism (VNTR). Results revealed a significant interaction between MAOA and smoking during pregnancy, indicating higher levels of aggressive behavior in young adults carrying the MAOA low-expressing genotype who had experienced prenatal nicotine exposure (n = 8, p = .025). In contrast, in carriers of the MAOA high-expressing genotype, maternal smoking during pregnancy had no effect on aggressive behavior during young adulthood (n = 20, p = .145). This study extends earlier findings demonstrating an interaction between MAOA genotype and prenatal nicotine exposure on aggressive behavior into young adulthood. The results point to the long-term adverse effects of smoking during pregnancy on the offspring's mental health, possibly underlining the importance of smoking cessation during pregnancy. According to the nature of the study (particularly sample size and power), analyses are exploratory and results need to be interpreted cautiously.}, language = {en} } @article{HohmannHohmTreutleinetal.2015, author = {Hohmann, Sarah and Hohm, Erika and Treutlein, Jens and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Association of norepinephrine transporter (NET, SLC6A2) genotype with ADHD-related phenotypes: Findings of a longitudinal study from birth to adolescence}, series = {Psychiatry research : the official publication of the International Society for Neuroimaging in Psychiatry}, volume = {226}, journal = {Psychiatry research : the official publication of the International Society for Neuroimaging in Psychiatry}, number = {2-3}, publisher = {Elsevier}, address = {Clare}, issn = {0165-1781}, doi = {10.1016/j.psychres.2014.12.029}, pages = {425 -- 433}, year = {2015}, abstract = {Variation in the gene encoding for the norepinephrine transporter (NET, SLC6A2) has repeatedly been linked with ADHD, although there is some inconsistency regarding the association with specific genes. The variants for which most consistent association has been found are the NET variants rs3785157 and rs28386840. Here, we tested for their association with ADHD diagnosis and ADHD-related phenotypes during development in a longitudinal German community sample. Children were followed from age 4 to age 15, using diagnostic interviews to assess ADHD. Between the ages of 8 and 15 years, the Child Behavior Checklist (CBCL) was administered to the primary caregivers. The continuous performance task (CPT) was performed at age 15. Controlling for possible confounders, we found that homozygous carriers of the major A allele of the functional promoter variant rs28386840 displayed a higher rate of ADHD lifetime diagnosis. Moreover, homozygous carriers of the minor T allele of rs3785157 were more likely to develop ADHD and showed higher scores on the CBCL externalizing behavior scales. Additionally, we found that individuals heterozygous for rs3785157 made fewer omission errors in the CPT than homozygotes. This is the first longitudinal study to report associations between specific NET variants and ADHD-related phenotypes during the course of development. (C) 2015 Elsevier Ireland Ltd. All rights reserved.}, language = {en} } @article{HohmannBeckerFellingeretal.2009, author = {Hohmann, Sarah and Becker, Katja and Fellinger, Johannes and Banaschewski, Tobias and Schmidt, Martin H. and Esser, G{\"u}nter and Laucht, Manfred}, title = {Evidence for epistasis between the 5-HTTLPR and the dopamine D4 receptor polymorphisms in externalizing behavior among 15-year-olds}, issn = {0300-9564}, doi = {10.1007/s00702-009-0290-1}, year = {2009}, abstract = {The present study aimed to clarify the functional role of genes in the dopamine and serotonin systems by examining whether polymorphisms in these genes are related to adolescent externalizing behavior either alone or in interaction with each other. Participants were selected from an ongoing prospective study of the outcome of early risk factors. At age 15 years, 298 adolescents (144 males, 154 females) completed the Youth Self Report, 296 primary caregivers the Child Behavior Checklist and 253 teachers the Teacher Report Form. DNA was genotyped for the DRD4 exon III VNTR and the 5-HTTLPR polymorphisms. Results revealed that individuals with the DRD4 7r allele reported significantly more externalizing behavior than carriers of other variants. In addition, a significant interaction emerged, indicating that adolescents carrying two copies of the 5-HTTLPR short allele and the DRD4 7r variant scored highest on aggressive and/or delinquent behavior compared to other genotypes. This result suggests an effect of 5-HTTLPR on externalizing behavior in the presence of DRD4 7r but no effect in its absence.}, language = {en} } @article{HohmannBuchmannWittetal.2012, author = {Hohmann, S. and Buchmann, Arlette F. and Witt, S. H. and Rietschel, M. and Jennen-Steinmetz, Christine and Schmidt, M. H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Increasing association between a neuropeptide Y promoter polymorphism and body mass index during the course of development}, series = {Pediatric obesity}, volume = {7}, journal = {Pediatric obesity}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {2047-6310}, doi = {10.1111/j.2047-6310.2012.00069.x}, pages = {453 -- 460}, year = {2012}, abstract = {Objective: To investigate the association of the neuropeptide Y (NPY) promoter polymorphism rs16147 with body mass index (BMI) during the course of development from infancy to adulthood. Design: Longitudinal, prospective study of a German community sample. Subjects: n = 306 young adults (139 males, 167 females). Measurements: Participants' body weight and height were assessed at the ages of 3 months and 2, 4.5, 8, 11, 15 and 19 years. NPY rs16147 was genotyped. Results: Controlling for a number of possible confounders, homozygote carriers of the rs16147 C allele exhibited significantly lower BMI scores when compared with individuals carrying the T allele. In addition, a significant genotype by age interaction emerged, indicating that the genotype effect increased during the course of development. Conclusions: This is the first longitudinal study to report an association between rs16147 and BMI during childhood and adolescence. The finding that this effect increased during the course of development may either be due to age-dependent alterations in gene expression or to maturation processes within the weight regulation circuits of the central nervous system.}, language = {en} } @article{HohmZohselSchmidtetal.2017, author = {Hohm, Erika and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Beeintr{\"a}chtigter Start ins Leben}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000234}, pages = {210 -- 220}, year = {2017}, abstract = {Postpartale Depressionen sind h{\"a}ufige und schwerwiegende psychische Erkrankungen mit ung{\"u}nstigem Einfluss auf die kindliche Entwicklung. Als Haupttransmissionsweg gilt die fr{\"u}he Mutter-Kind-Interaktion. {\"U}ber die langfristigen Auswirkungen auf die Kinder im Erwachsenenalter und die Rolle der Interaktion liegen kaum Ergebnisse vor. Im Rahmen der Mannheimer Risikokinderstudie wurden postpartale Depressionen bis zwei Jahre nach der Geburt erfasst. Die kindliche Entwicklung wurde fortlaufend und die Mutter-Kind-Interaktion im Alter von 3 Monaten standardisiert erhoben. 28 Kinder postpartal depressiver und 107 Kinder gesunder M{\"u}tter konnten mit 25 Jahren untersucht werden. Beeintr{\"a}chtigungen der kognitiven und psychischen Entwicklung bei Kindern postpartal depressiver M{\"u}tter waren bis ins Erwachsenenalter nachweisbar. Responsives bzw. sensitives m{\"u}tterliches Verhalten wirkte der negativen Entwicklung entgegen. Dies betont die Bedeutung einer hohen Qualit{\"a}t der Mutter-Kind-Interaktion f{\"u}r die Entwicklung von Risikokindern.}, language = {de} } @misc{HohmZohselSchmidtetal.2017, author = {Hohm, Erika and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Beeintr{\"a}chtigter Start ins Leben}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {692}, issn = {1866-8364}, doi = {10.25932/publishup-43340}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-433406}, pages = {37}, year = {2017}, abstract = {Postpartale Depressionen sind h{\"a}ufige und schwerwiegende psychische Erkrankungen mit ung{\"u}nstigem Einfluss auf die kindliche Entwicklung. Als Haupttransmissionsweg gilt die fr{\"u}he Mutter-Kind-Interaktion. {\"U}ber die langfristigen Auswirkungen auf die Kinder im Erwachsenenalter und die Rolle der Interaktion liegen kaum Ergebnisse vor. Im Rahmen der Mannheimer Risikokinderstudie wurden postpartale Depressionen bis zwei Jahre nach der Geburt erfasst. Die kindliche Entwicklung wurde fortlaufend und die Mutter-Kind-Interaktion im Alter von 3 Monaten standardisiert erhoben. 28 Kinder postpartal depressiver und 107 Kinder gesunder M{\"u}tter konnten mit 25 Jahren untersucht werden. Beeintr{\"a}chtigungen der kognitiven und psychischen Entwicklung bei Kindern postpartal depressiver M{\"u}tter waren bis ins Erwachsenenalter nachweisbar. Responsives bzw. sensitives m{\"u}tterliches Verhalten wirkte der negativen Entwicklung entgegen. Dies betont die Bedeutung einer hohen Qualit{\"a}t der Mutter-Kind-Interaktion f{\"u}r die Entwicklung von Risikokindern.}, language = {de} } @article{HohmLauchtZohseletal.2017, author = {Hohm, Erika and Laucht, Manfred and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias}, title = {Resilienz und Ressourcen im Verlauf der Entwicklung}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000236}, pages = {230 -- 239}, year = {2017}, abstract = {Anhand von Daten der Mannheimer Risikokinderstudie, die sich mit der langfristigen Entwicklung von Kindern mit unterschiedlichen Risikobelastungen besch{\"a}ftigt, wird gezeigt, wie Schutzfaktoren aufseiten des Kindes und seines famili{\"a}ren Umfelds im Verlauf der Entwicklung wirksam werden und zur Entstehung von Resilienz beitragen k{\"o}nnen. Eine besondere Rolle kommt dabei positiven fr{\"u}hen Eltern-Kind-Beziehungen zu (sowohl Mutter- als auch Vater-Kind-Interaktionen). Daneben spielen auch Interaktionserfahrungen im Alter von zwei Jahren des Kindes eine bedeutsame Rolle; diese sch{\"u}tzen Risikokinder davor, eine ung{\"u}nstige Entwicklung zu nehmen und tragen dazu bei, dass sich Kinder, die in psychosozialen Hochrisikofamilien aufwachsen, trotz ung{\"u}nstiger „Startbedingungen" positiv entwickeln. Neben Merkmalen der sozialen Umwelt nehmen auch sprachliche, sozial-emotionale und internale Kompetenzen des Kindes im Entwicklungsverlauf eine wichtige Rolle ein. Diese Kompetenzen erm{\"o}glichen es Risikokindern auch unter widrigen Lebensumst{\"a}nden (psychosoziale Hochrisikofamilien, Aufwachsen in Armutsverh{\"a}ltnissen) erfolgreich zu bestehen. Dar{\"u}ber hinaus zeigt die Arbeit, dass Resilienz ein Pers{\"o}nlichkeitsmerkmal ist, das ab dem fr{\"u}hen Erwachsenenalter eine hohe Stabilit{\"a}t besitzt. Mit diesen Befunden verweist die Arbeit auf die große Bedeutung der Resilienz bei der Vorhersage der langfristigen Entwicklung von Risikokindern.}, language = {de} } @article{HeinrichBuchmannZohseletal.2015, author = {Heinrich, Angela and Buchmann, Arlette F. and Zohsel, Katrin and Dukal, Helene and Frank, Josef and Treutlein, Jens and Nieratschker, Vanessa and Witt, Stephanie H. and Brandeis, Daniel and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred and Rietschel, Marcella}, title = {Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence}, series = {Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man}, volume = {45}, journal = {Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man}, number = {5}, publisher = {Springer}, address = {New York}, issn = {0001-8244}, doi = {10.1007/s10519-015-9721-y}, pages = {529 -- 536}, year = {2015}, abstract = {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.}, language = {en} } @article{BuchmannZohselBlomeyeretal.2014, author = {Buchmann, Arlette F. and Zohsel, Katrin and Blomeyer, Dorothea and Hohm, Erika and Hohmann, Sarah and Jennen-Steinmetz, Christine and Treutlein, Jens and Becker, Katja and Banaschewski, Tobias and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Poustka, Luise and Zimmermann, Ulrich S. and Laucht, Manfred}, title = {Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults}, series = {Psychopharmacology}, volume = {231}, journal = {Psychopharmacology}, number = {16}, publisher = {Springer}, address = {New York}, issn = {0033-3158}, doi = {10.1007/s00213-014-3484-7}, pages = {3089 -- 3097}, year = {2014}, abstract = {Considerable evidence suggests that genetic factors combine with environmental influences to impact on the development of aggressive behavior. A genetic variant that has repeatedly been reported to render individuals more sensitive to the presence of adverse experiences, including stress exposure during fetal life, is the seven-repeat allele of the dopamine D4 receptor (DRD4) gene. The present investigation concentrated on the interplay of prenatal maternal stress and DRD4 genotype in predicting self-reported aggression in young adults. As disruption of the hypothalamic-pituitary-adrenal system has been discussed as a pathophysiological pathway to aggression, cortisol stress reactivity was additionally examined. As part of an epidemiological cohort study, prenatal maternal stress was assessed by maternal interview 3 months after childbirth. Between the ages of 19 and 23 years, 298 offspring (140 males, 158 females) completed the Young Adult Self-Report to measure aggressive behavior and were genotyped for the DRD4 gene. At 19 years, 219 participants additionally underwent the Trier Social Stress Test to determine cortisol reactivity. Extending earlier findings with respect to childhood antisocial behavior, the results revealed that, under conditions of higher prenatal maternal stress, carriers of the DRD4 seven-repeat allele displayed more aggression in adulthood (p = 0.032). Moreover, the same conditions which seemed to promote aggression were found to predict attenuated cortisol secretion (p = 0.028). This is the first study to indicate a long-term impact of prenatal stress exposure on the cortisol stress response depending on DRD4 genotype.}, language = {en} } @article{BuchmannSchmidBlomeyeretal.2010, author = {Buchmann, Arlette F. and Schmid, Brigitte and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Mann, Karl F. and Laucht, Manfred}, title = {Drinking against unpleasant emotions : possible outcome of early onset of alcohol use?}, issn = {0145-6008}, doi = {10.1111/j.1530-0277.2010.01180.x}, year = {2010}, abstract = {Background: Recent animal and human studies indicate that the exposure to alcohol during early adolescence increases the risk for heavy alcohol use in response to stress. The purpose of this study was to examine whether this effect may be the consequence of a higher susceptibility to develop "drinking to cope" motives among early initiators. Methods: Data from 320 participants were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study. Structured interviews at age 15 and 19 were used to assess age at first alcohol experience and drunkenness. The young adults completed questionnaires to obtain information about the occurrence of stressful life events during the past 4 years and current drinking habits. In addition, alcohol use under conditions of negative states was assessed with the Inventory of Drinking Situations. Results: The probability of young adults' alcohol use in situations characterized by unpleasant emotions was significantly increased the earlier they had initiated the use of alcohol, even when controlling for current drinking habits and stressful life events. Similar results were obtained for the age at first drunkenness. Conclusions: The findings strengthen the hypothesis that alcohol experiences during early adolescence facilitate drinking to regulate negative affect as an adverse coping strategy which may represent the starting point of a vicious circle comprising drinking to relieve stress and increased stress as a consequence of drinking.}, language = {en} } @article{BuchmannSchmidBlomeyeretal.2009, author = {Buchmann, Arlette F. and Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Treutlein, Jens and Zimmermann, Ulrich S. and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Rietschel, Marcella and Schumann, Gunter and Laucht, Manfred}, title = {Impact of age at first drink on vulnerability to alcohol-related problems : testing the marker hypothesis in a prospective study of young adults}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2009.02.006}, year = {2009}, abstract = {There is ample evidence that the early initiation of alcohol use is a risk factor for the development of later alcohol-related problems. The purpose of the current study was to examine whether this association can be explained by indicators of a common underlying susceptibility or whether age at drinking onset may be considered as an independent predictor of later drinking behavior, suggesting a potential causal relationship. Participants were drawn from a prospective cohort study of the long-term outcomes of early risk factors followed up from birth onwards. Structured interviews were administered to 304 participants to assess age at first drink and current drinking behavior. Data on risk factors, including early family adversity, parental alcohol use, childhood psychopathology and stressful life events, were repeatedly collected during childhood using standardized parent interviews. In addition, information on genotype was considered. Results confirmed previous work demonstrating that hazardous alcohol consumption is related to early-adolescent drinking onset. A younger age of first drink was significantly predicted by 5-HTTLPR genotype and the degree of preceding externalizing symptoms, and both factors were related to increased consumption or harmful alcohol use at age 19. However, even after controlling for these potential explanatory factors, earlier age at drinking onset remained a strong predictor of heavy alcohol consumption in young adulthood. The present longitudinal study adds to the current literature indicating that the early onset - adult hazardous drinking association cannot solely be attributed to shared genetic and psychopathologic risk factors as examined in this study.}, language = {en} } @article{BuchmannKopfWestphaletal.2010, author = {Buchmann, Arlette F. and Kopf, Daniel and Westphal, Sabine and Lederbogen, Florian and Banaschewski, Tobias and Esser, G{\"u}nter and Schmidt, Martin H. and Zimmermann, Ulrich S. and Laucht, Manfred and Deuschle, Michael}, title = {Impact of early parental child-rearing behavior on young adults' cardiometabolic risk profile : a prospective study}, issn = {0033-3174}, doi = {10.1097/Psy.0b013e3181c88343}, year = {2010}, abstract = {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.}, language = {en} } @article{BuchmannHolzBoeckerSchlieretal.2014, author = {Buchmann, Arlette F. and Holz, Nathalie and Boecker-Schlier, Regina and Blomeyer, Dorothea and Rietschel, Marcella and Witt, Stephanie H. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Zimmermann, Ulrich S. and Laucht, Manfred}, title = {Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {24}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {6}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2013.12.001}, pages = {837 -- 845}, year = {2014}, abstract = {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.}, language = {en} } @article{BuchmannHohmWittetal.2015, author = {Buchmann, Arlette F. and Hohm, Erika and Witt, Stephanie H. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents}, series = {Journal of neural transmission}, volume = {122}, journal = {Journal of neural transmission}, number = {3}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-014-1266-3}, pages = {455 -- 463}, year = {2015}, abstract = {Enhanced endocannabinoid signaling has been implicated in typically adolescent behavioral features such as increased risk-taking, impulsivity and novelty seeking. Research investigating the impact of genetic variants in the cannabinoid receptor 1 gene (CNR1) and of early rearing conditions has demonstrated that both factors contribute to the prediction of impulsivity-related phenotypes. The present study aimed to test the hypothesis of an interaction of the two most studied CNR1 polymorphisms rs806379 and rs1049353 with early psychosocial adversity in terms of affecting impulsivity in 15-year-olds from an epidemiological cohort sample followed since birth. In 323 adolescents (170 girls, 153 boys), problems of impulse control and novelty seeking were assessed using parent-report and self-report, respectively. Exposure to early psychosocial adversity was determined in a parent interview conducted at the age of 3 months. The results indicated that impulsivity increased following exposure to early psychosocial adversity, with this increase being dependent on CNR1 genotype. In contrast, while individuals exposed to early adversity scored higher on novelty seeking, no significant impact of genotype or the interaction thereof was detected. This is the first evidence to suggest that the interaction of CNR1 gene variants with the experience of early life adversity may play a role in determining adolescent impulsive behavior. However, given that the reported findings are obtained in a high-risk community sample, results are restricted in terms of interpretation and generalization. Future research is needed to replicate these findings and to identify the mediating mechanisms underlying this effect.}, language = {en} } @article{BuchmannHellwegRietscheletal.2013, author = {Buchmann, Arlette F. and Hellweg, Rainer and Rietschel, Marcella and Treutlein, Jens and Witt, Stephanie H. and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred and Deuschle, Michael}, title = {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}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {23}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {8}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2012.09.003}, pages = {902 -- 909}, year = {2013}, abstract = {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.}, language = {en} } @article{BuchmannBlomeyerJennenSteinmetzetal.2013, author = {Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Early smoking onset may promise initial pleasurable sensations and later addiction}, series = {Addiction biology}, volume = {18}, journal = {Addiction biology}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1369-1600}, doi = {10.1111/j.1369-1600.2011.00377.x}, pages = {947 -- 954}, year = {2013}, abstract = {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.}, language = {en} } @misc{BoeckerSchlierHolzBuchmannetal.2014, author = {Boecker-Schlier, Regina and Holz, Nathalie E. and Buchmann, Arlette F. and Blomeyer, Dorothea and Plichta, Michael M. and Wolf, Isabella and Baumeister, Sarah and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years}, series = {PLoS one}, volume = {9}, journal = {PLoS one}, number = {10}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0112155}, pages = {1}, year = {2014}, language = {en} } @article{BoeckerSchlierHolzBuchmannetal.2014, author = {Boecker-Schlier, Regina and Holz, Nathalie E. and Buchmann, Arlette F. and Blomeyer, Dorothea and Plichta, Michael M. and Wolf, Isabella and Baumeister, Sarah and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years}, series = {PLoS one}, volume = {9}, journal = {PLoS one}, number = {8}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0104185}, pages = {13}, year = {2014}, abstract = {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.}, language = {en} } @article{BlomeyerFriemelBuchmannetal.2013, author = {Blomeyer, Dorothea and Friemel, Chris M. and Buchmann, Arlette F. and Banaschewski, Tobias and Laucht, Manfred and Schneider, Miriam}, title = {Impact of pubertal stage at first drink on adult drinking behavior}, series = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, volume = {37}, journal = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, number = {10}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0145-6008}, doi = {10.1111/acer.12154}, pages = {1804 -- 1811}, year = {2013}, abstract = {BackgroundEarly alcohol use is one of the strongest predictors of later alcohol use disorders, with early use usually taking place during puberty. Many researchers have suggested drinking during puberty as a potential biological basis of the age at first drink (AFD) effect. However, the influence of the pubertal phase at alcohol use initiation on subsequent drinking in later life has not been examined so far. MethodsPubertal stage at first drink (PSFD) was determined in N=283 young adults (131 males, 152 females) from an epidemiological cohort study. At ages 19, 22, and 23years, drinking behavior (number of drinking days, amount of alcohol consumed, hazardous drinking) was assessed using interview and questionnaire methods. Additionally, an animal study examined the effects of pubertal or adult ethanol (EtOH) exposure on voluntary EtOH consumption in later life in 20 male Wistar rats. ResultsPSFD predicted drinking behavior in humans in early adulthood, indicating that individuals who had their first drink during puberty displayed elevated drinking levels compared to those with postpubertal drinking onset. These findings were corroborated by the animal study, in which rats that received free access to alcohol during the pubertal period were found to consume more alcohol as adults, compared to the control animals that first came into contact with alcohol during adulthood. ConclusionsThe results point to a significant role of stage of pubertal development at first contact with alcohol for the development of later drinking habits. Possible biological mechanisms and implications for prevention are discussed.}, language = {en} } @article{BlomeyerBuchmannSchmidetal.2011, author = {Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Banaschewski, Tobias and Laucht, Manfred}, title = {Age at first drink moderates the impact of current stressful life events on drinking behavior in young adults}, series = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, volume = {35}, journal = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, number = {6}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0145-6008}, doi = {10.1111/j.1530-0277.2011.01447.x}, pages = {1142 -- 1148}, year = {2011}, abstract = {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.}, language = {en} } @article{BlomeyerBuchmannLascorzetal.2013, author = {Blomeyer, Dorothea and Buchmann, Arlette F. and Lascorz, Jesus and Zimmermann, Ulrich S. and Esser, G{\"u}nter and Desrivieres, Sylvane and Schmidt, Martin H. and Banaschewski, Tobias and Schumann, Gunter and Laucht, Manfred}, title = {Association of PER2 genotype and stressful life events with alcohol drinking in young adults}, series = {PLoS one}, volume = {8}, journal = {PLoS one}, number = {3}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0059136}, pages = {7}, year = {2013}, abstract = {Background: Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking. Methods: Data were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview. Results: Individuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72\% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress. Conclusions: These findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.}, language = {en} } @article{BenderRellumFreitagetal.2012, author = {Bender, Stephan and Rellum, Thomas and Freitag, Christine and Resch, Franz and Rietschel, Marcella and Treutlein, Jens and Jennen-Steinmetz, Christine and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Dopamine inactivation efficacy related to functional DAT1 and COMT variants influences motor response evaluation}, series = {PLoS one}, volume = {7}, journal = {PLoS one}, number = {5}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0037814}, pages = {13}, year = {2012}, abstract = {Background: Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. Methods: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val(158) Met and two DAT1 polymorphisms (variable number tandem repeats in the 3'-untranslated region and in intron 8). Results: The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500-1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. Conclusions: Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming.}, language = {en} } @article{BenderRellumFreitagetal.2012, author = {Bender, Stephan and Rellum, Thomas and Freitag, Christine and Resch, Franz and Rietschel, Marcella and Treutlein, Jens and Jennen-Steinmetz, Christine and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Time-Resolved influences of functional DAT1 and COMT variants on visual perception and post-processing}, series = {PLoS one}, volume = {7}, journal = {PLoS one}, number = {7}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0041552}, pages = {12}, year = {2012}, abstract = {Background: Dopamine plays an important role in orienting and the regulation of selective attention to relevant stimulus characteristics. Thus, we examined the influences of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of visual processing in a contingent negative variation (CNV) task. Methods: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as preceding visual evoked potential components were assessed. Results: Significant additive main effects of DAT1 and COMT on the occipito-temporal early CNV were observed. In addition, there was a trend towards an interaction between the two polymorphisms. Source analysis showed early CNV generators in the ventral visual stream and in frontal regions. There was a strong negative correlation between occipito-temporal visual post-processing and the frontal early CNV component. The early CNV time interval 500-1000 ms after the visual cue was specifically affected while the preceding visual perception stages were not influenced. Conclusions: Late visual potentials allow the genomic imaging of dopamine inactivation effects on visual post-processing. The same specific time-interval has been found to be affected by DAT1 and COMT during motor post-processing but not motor preparation. We propose the hypothesis that similar dopaminergic mechanisms modulate working memory encoding in both the visual and motor and perhaps other systems.}, language = {en} } @article{BenderBanaschewskiRoessneretal.2015, author = {Bender, Stephan and Banaschewski, Tobias and R{\"o}ßner, Veit and Klein, Christoph and Rietschel, Marcella and Feige, Bernd and Brandeis, Daniel and Laucht, Manfred}, title = {Variability of single trial brain activation predicts fluctuations in reaction time}, series = {Biological psychology}, volume = {106}, journal = {Biological psychology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0301-0511}, doi = {10.1016/j.biopsycho.2015.01.013}, pages = {50 -- 60}, year = {2015}, abstract = {Brain activation stability is crucial to understanding attention lapses. EEG methods could provide excellent markers to assess neuronal response variability with respect to temporal (intertrial coherence) and spatial variability (topographic consistency) as well as variations in activation intensity (low frequency variability of single trial global field power). We calculated intertrial coherence, topographic consistency and low frequency amplitude variability during target P300 in a continuous performance test in 263 15-year-olds from a cohort with psychosocial and biological risk factors. Topographic consistency and low frequency amplitude variability predicted reaction time fluctuations (RTSD) in a linear model. Higher RTSD was only associated with higher psychosocial adversity in the presence of the homozygous 6R-10R dopamine transporter haplotype. We propose that topographic variability of single trial P300 reflects noise as well as variability in evoked cortical activation patterns. Dopaminergic neuromodulation interacted with environmental and biological risk factors to predict behavioural reaction time variability. (C) 2015 Elsevier B.V. All rights reserved.}, language = {en} } @article{BeckerBlomeyerElFaddaghetal.2010, author = {Becker, Katja and Blomeyer, Dorothea and El-Faddagh, Mahha and Esser, G{\"u}nter and Schmidt, Martin H. and Banaschewski, Tobias and Laucht, Manfred}, title = {From regulatory problems in infancy to attention-deficit/hyperactivity disorder in childhood : a moderating role for the dopamine D4 receptor gene?}, issn = {0022-3476}, doi = {10.1016/j.jpeds.2009.12.005}, year = {2010}, abstract = {To examine whether the dopamine receptor D4 gene (DRD4) exon III VNTR moderates the risk of infants with regulatory disorders for developing attention-deficit/hyperactivity disorder (ADHD) later in childhood. In a prospective longitudinal study of children at risk for later psychopathology, 300 participants were assessed for regulatory problems in infancy, DRD4 genotype, and ADHD symptoms and diagnoses from childhood to adolescence. To examine a potential moderating effect on ADHD measures, linear and logistic regressions were computed. Models were fit for the main effects of the DRD4 genotype (presence or absence of the 7r allele) and regulatory problems (presence or absence), with the addition of the interaction term. All models were controlled for sex, family adversity, and obstetric risk status. In children without the DRD4-7r allele, a history of regulatory problems in infancy was unrelated to later ADHD. But in children with regulatory problems in infancy, the additional presence of the DRD4-7r allele increased the risk for ADHD in childhood. The DRD4 genotype seems to moderate the association between regulatory problems in infancy and later ADHD. A replication study is needed before further conclusions can be drawn, however.}, language = {en} } @article{AdamoBaumeisterHohmannetal.2015, author = {Adamo, Nicoletta and Baumeister, Sarah and Hohmann, Sarah and Wolf, Isabella and Holz, Nathalie and Boecker-Schlier, Regina and Laucht, Manfred and Banaschewski, Tobias and Brandeis, Daniel}, title = {Frequency-specific coupling between trial-to-trial fluctuations of neural responses and response-time variability}, series = {Journal of neural transmission}, volume = {122}, journal = {Journal of neural transmission}, number = {8}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-015-1382-8}, pages = {1197 -- 1202}, year = {2015}, abstract = {We assessed intra-individual variability of response times (RT) and single-trial P3 amplitudes following targets in healthy adults during a Flanker/NO-GO task. RT variability and variability of the neural responses coupled at the faster frequencies examined (0.07-0.17 Hz) at Pz, the target-P3 maxima, despite non-significant associations for overall variability (standard deviation, SD). Frequency-specific patterns of variability in the single-trial P3 may help to understand the neurophysiology of RT variability and its explanatory models of attention allocation deficits beyond intra-individual variability summary indices such as SD.}, language = {en} }