@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{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{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{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{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{PitzerJennenSteinmetzEsseretal.2011, author = {Pitzer, Martina and Jennen-Steinmetz, Christine and Esser, G{\"u}nter and Schmidt, Martin H. and Laucht, Manfred}, title = {Prediction of preadolescent depressive symptoms from child temperament, maternal distress, and gender results of a prospective, longitudinal study}, series = {Journal of developmental and behavioral pediatrics}, volume = {32}, journal = {Journal of developmental and behavioral pediatrics}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0196-206X}, doi = {10.1097/DBP.0b013e3181f4a474}, pages = {18 -- 26}, year = {2011}, abstract = {Objective: The delineation of developmental pathways to juvenile depressive symptoms is of major clinical interest because these are known to be predictive for adult mood disorders and for a range of other mental health problems. This study investigates the impact of child temperament and early maternal distress, both of which are known to influence children's emotional development, on preadolescent depression. Methods: In a prospective, longitudinal at-risk sample (163 boys, 178 girls), we assessed temperament at the age of 3 months and at 2 years, 4.5 years, and 8 years, respectively, and chronic maternal distress during infancy. Hierarchical linear regression analysis was used to investigate the prediction of depressive symptoms at the age of 11 years measured by the Child Depression Inventory. In addition, we controlled for psychosocial and obstetric perinatal risks and gender. Results: Psychosocial risks and self-control temperament made significant independent contributions to preadolescent depression, whereas fearful, difficult temperament and obstetric risks were unrelated to depressive outcome. Interestingly, a clear gender difference emerged with a significant prediction from maternal distress only in girls. Conclusions: Our data extend previous findings of a concurrent association between regulative temperament and juvenile depression to a predictive view. Furthermore, the results point toward gender-specific pathways to preadolescent depression and support earlier findings indicating that subclinical maternal distress may exert as detrimental effects on child development as clinical depression.}, language = {en} } @article{HolzBoeckerSchlierJennenSteinmetzetal.2016, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Jennen-Steinmetz, Christine 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 = {Positive coping styles and perigenual ACC volume: two related mechanisms for conferring resilience?}, series = {Frontiers in human neuroscience}, volume = {11}, journal = {Frontiers in human neuroscience}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsw005}, pages = {813 -- 820}, year = {2016}, abstract = {Stress exposure has been linked to increased rates of depression and anxiety in adults, particularly in females, and has been associated with maladaptive changes in the anterior cingulate cortex (ACC), which is an important brain structure involved in internalizing disorders. Coping styles are important mediators of the stress reaction by establishing homeostasis, and may thus confer resilience to stress-related psychopathology. Anatomical scans were acquired in 181 healthy participants at age 25 years. Positive coping styles were determined using a self-report questionnaire (German Stress Coping Questionnaire, SVF78) at age 22 years. Adult anxiety and depression symptoms were assessed at ages 22, 23 and 25 years with the Young Adult Self-Report. Information on previous internalizing diagnoses was obtained by diagnostic interview (2-19 years). Positive coping styles were associated with increased ACC volume. ACC volume and positive coping styles predicted anxiety and depression in a sex-dependent manner with increased positive coping and ACC volume being related to lower levels of psychopathology in females, but not in males. These results remained significant when controlled for previous internalizing diagnoses. These findings indicate that positive coping styles and ACC volume are two linked mechanisms, which may serve as protective factors against internalizing disorders.}, 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.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{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} }