TY - JOUR A1 - Holz, Nathalie E. A1 - Zohsel, Katrin A1 - Laucht, Manfred A1 - Banaschewski, Tobias A1 - Hohmann, Sarah A1 - Brandeis, Daniel T1 - Gene x environment interactions in conduct disorder BT - Implications for future treatments JF - Neuroscience & biobehavioral reviews : official journal of the International Behavioral Neuroscience Society N2 - 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. KW - Gene-environment interaction KW - Conduct disorder KW - Aggression KW - Externalizing behavior KW - fMRI Y1 - 2016 U6 - https://doi.org/10.1016/j.neubiorev.2016.08.017 SN - 0149-7634 SN - 1873-7528 VL - 91 SP - 239 EP - 258 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Millenet, Sabina A1 - Laucht, Manfred A1 - Hohm, Erika A1 - Jennen-Steinmetz, Christine A1 - Hohmann, Sarah A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Zohsel, Katrin T1 - Sex-specific trajectories of ADHD symptoms from adolescence to young adulthood JF - European child and adolescent psychiatry : offical journal of the European Society for Child and Adolescent Psychiatry N2 - 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. KW - ADHD KW - Sex KW - Self-report KW - Longitudinal study Y1 - 2018 U6 - https://doi.org/10.1007/s00787-018-1129-9 SN - 1018-8827 SN - 1435-165X VL - 27 IS - 8 SP - 1067 EP - 1075 PB - Springer CY - New York ER - TY - JOUR A1 - Hohmann, Sarah A1 - Becker, Katja A1 - Fellinger, Johannes A1 - Banaschewski, Tobias A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Laucht, Manfred T1 - Evidence for epistasis between the 5-HTTLPR and the dopamine D4 receptor polymorphisms in externalizing behavior among 15-year-olds N2 - 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. Y1 - 2009 UR - http://www.springerlink.com/content/101493 U6 - https://doi.org/10.1007/s00702-009-0290-1 SN - 0300-9564 ER - TY - JOUR A1 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Baumeister, Sarah A1 - Hohm, Erika A1 - Zohsel, Katrin A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Hohmann, Sarah A1 - Wolf, Isabella A1 - Plichta, Michael M. A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Effect of prenatal exposure to tobacco smoke on inhibitory control neuroimaging results from a 25-Year prospective study JF - JAMA psychiatry N2 - IMPORTANCE: There is accumulating evidence relating maternal smoking during pregnancy to attention-deficit/hyperactivity disorder (ADHD) without elucidating specific mechanisms. Research investigating the neurobiological underpinnings of this disorder has implicated deficits during response inhibition. Attempts to uncover the effect of prenatal exposure to nicotine on inhibitory control may thus be of high clinical importance. MAIN OUTCOMES AND MEASURES: Functional magnetic resonance imaging response, morphometric data, lifetime ADHD symptoms, and novelty seeking. RESULTS: Participants prenatally exposed to nicotine exhibited a weaker response in the anterior cingulate cortex (t(168) = 4.46; peak Montreal Neurological Institute [MNI] coordinates x = -2, y = 20, z = 30; familywise error [FWE]-corrected P = .003), the right inferior frontal gyrus (t(168) = 3.65; peak MNI coordinates x = 44, y = 38, z = 12; FWE-corrected P = .04), the left inferior frontal gyrus (t(168) = 4.09; peak MNI coordinates x = -38, y = 36, z = 8; FWE-corrected P = .009), and the supramarginal gyrus (t(168) = 5.03; peak MNI coordinates x = 64, y = -28, z = 22; FWE-corrected P = .02) during the processing of the NoGo compared to neutral stimuli, while presenting a decreased volume in the right inferior frontal gyrus. These findings were obtained irrespective of the adjustment of confounders, ADHD symptoms, and novelty seeking. There was an inverse relationship between inferior frontal gyrus activity and ADHD symptoms and between anterior cingulate cortex activity and novelty seeking. CONCLUSIONS AND RELEVANCE: These findings point to a functional involvement of prenatal exposure to tobacco smoke in neural alterations similar to ADHD, which underlines the importance of smoking prevention treatments. Y1 - 2014 U6 - https://doi.org/10.1001/jamapsychiatry.2014.786 SN - 2168-622X SN - 2168-6238 VL - 71 IS - 7 SP - 786 EP - 796 PB - American Veterinary Medical Association CY - Chicago ER - TY - JOUR A1 - Adamo, Nicoletta A1 - Baumeister, Sarah A1 - Hohmann, Sarah A1 - Wolf, Isabella A1 - Holz, Nathalie A1 - Boecker-Schlier, Regina A1 - Laucht, Manfred A1 - Banaschewski, Tobias A1 - Brandeis, Daniel T1 - Frequency-specific coupling between trial-to-trial fluctuations of neural responses and response-time variability JF - Journal of neural transmission N2 - 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. KW - Intra-individual response-time variability KW - Event-related potential KW - Cognitive control KW - Attention deficit Y1 - 2015 U6 - https://doi.org/10.1007/s00702-015-1382-8 SN - 0300-9564 SN - 1435-1463 VL - 122 IS - 8 SP - 1197 EP - 1202 PB - Springer CY - Wien ER - TY - JOUR A1 - Poustka, Luise A1 - Zohsel, Katrin A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Schmid, Brigitte A1 - Trautmann-Villalba, Patricia A1 - Hohmann, Sarah A1 - Becker, Katja A1 - Esser, Günter A1 - Schmidt, Martin H. A1 - Brandeis, Daniel A1 - Banaschewski, Tobias A1 - Laucht, Manfred T1 - Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis JF - Journal of psychiatric research N2 - 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. KW - Dysregulation KW - Childhood KW - Infant regulatory problems KW - Parenting quality KW - DRD4 KW - Gene-environment interaction Y1 - 2015 U6 - https://doi.org/10.1016/j.psychires.2015.08.018 SN - 0022-3956 SN - 1879-1379 VL - 70 SP - 83 EP - 90 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Buchmann, Arlette F. A1 - Zohsel, Katrin A1 - Blomeyer, Dorothea A1 - Hohm, Erika A1 - Hohmann, Sarah A1 - Jennen-Steinmetz, Christine A1 - Treutlein, Jens A1 - Becker, Katja A1 - Banaschewski, Tobias A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Brandeis, Daniel A1 - Poustka, Luise A1 - Zimmermann, Ulrich S. A1 - Laucht, Manfred T1 - Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults JF - Psychopharmacology N2 - 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. KW - Prenatal stress KW - Aggression KW - Cortisol KW - DRD4 KW - Gene-environment interaction Y1 - 2014 U6 - https://doi.org/10.1007/s00213-014-3484-7 SN - 0033-3158 SN - 1432-2072 VL - 231 IS - 16 SP - 3089 EP - 3097 PB - Springer CY - New York ER - TY - JOUR A1 - Holz, Nathalie A1 - Boecker-Schlier, Regina A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Baumeister, Sarah A1 - Hohmann, Sarah A1 - Jennen-Steinmetz, Christine A1 - Wolf, Isabella A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Plichta, Michael M. A1 - Meyer-Lindenberg, Andreas A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression JF - Cerebral cortex N2 - Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOAx CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders. KW - aggression KW - amygdala KW - fMRI KW - life stress KW - MAOA Y1 - 2016 U6 - https://doi.org/10.1093/cercor/bhu249 SN - 1047-3211 SN - 1460-2199 VL - 26 SP - 904 EP - 914 PB - Oxford Univ. Press CY - Cary ER - TY - JOUR A1 - Hohmann, Sarah A1 - Zohsel, Katrin A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Holz, Nathalie A1 - Boecker-Schlier, Regina A1 - Jennen-Steinmetz, Christine A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Hohm, Erika A1 - Laucht, Manfred T1 - Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood JF - Journal of neural transmission N2 - 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′ 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. KW - MAOA KW - Smoking during pregnancy KW - Interaction KW - Aggression KW - Longitudinal KW - Young adulthood Y1 - 2016 U6 - https://doi.org/10.1007/s00702-016-1582-x SN - 0300-9564 SN - 1435-1463 VL - 123 SP - 885 EP - 894 PB - Springer CY - Wien ER - TY - JOUR A1 - Hohmann, Sarah A1 - Hohm, Erika A1 - Treutlein, Jens A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Association of norepinephrine transporter (NET, SLC6A2) genotype with ADHD-related phenotypes: Findings of a longitudinal study from birth to adolescence JF - Psychiatry research : the official publication of the International Society for Neuroimaging in Psychiatry N2 - 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. KW - Attention-deficit/hyperactivity disorder KW - Norepinephrine transporter KW - Genetic association KW - Polymorphism KW - Molecular heterosis KW - Continuous performance task Y1 - 2015 U6 - https://doi.org/10.1016/j.psychres.2014.12.029 SN - 0165-1781 VL - 226 IS - 2-3 SP - 425 EP - 433 PB - Elsevier CY - Clare ER - TY - JOUR A1 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Hohm, Erika A1 - Zohsel, Katrin A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Baumeister, Sarah A1 - Hohmann, Sarah A1 - Wolf, Isabella A1 - Plichta, Michael M. A1 - Esser, Günter A1 - Schmidt, Martin A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - The Long-Term Impact of Early Life Poverty on Orbitofrontal Cortex Volume in Adulthood: Results from a Prospective Study Over 25 Years JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology N2 - 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. Y1 - 2015 U6 - https://doi.org/10.1038/npp.2014.277 SN - 0893-133X SN - 1740-634X VL - 40 IS - 4 SP - 996 EP - 1004 PB - Nature Publ. Group CY - London ER -