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 - TY - JOUR A1 - Buchmann, Arlette F. A1 - Hohm, Erika A1 - Witt, Stephanie H. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents JF - Journal of neural transmission N2 - 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. KW - CNR1 KW - Impulsivity KW - Early psychosocial adversity KW - Adolescence Y1 - 2015 U6 - https://doi.org/10.1007/s00702-014-1266-3 SN - 0300-9564 SN - 1435-1463 VL - 122 IS - 3 SP - 455 EP - 463 PB - Springer CY - Wien ER - TY - JOUR A1 - Holz, Nathalie E. A1 - Buchmann, Arlette F. A1 - Boecker-Schlier, Regina A1 - Blomeyer, Dorothea A1 - Baumeister, Sarah A1 - Wolf, Isabella A1 - Rietschel, Marcella A1 - Witt, Stephanie H. A1 - Plichta, Michael M. A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume JF - Brain structure & function N2 - 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. KW - FKBP5 KW - Childhood adversity KW - Amygdala KW - fMRI KW - Connectivity KW - Voxel-based morphometry Y1 - 2015 U6 - https://doi.org/10.1007/s00429-014-0729-5 SN - 1863-2653 SN - 1863-2661 VL - 220 IS - 3 SP - 1355 EP - 1368 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Heinrich, Angela A1 - Buchmann, Arlette F. A1 - Zohsel, Katrin A1 - Dukal, Helene A1 - Frank, Josef A1 - Treutlein, Jens A1 - Nieratschker, Vanessa A1 - Witt, Stephanie H. A1 - Brandeis, Daniel A1 - Schmidt, Martin H. A1 - Esser, Günter A1 - Banaschewski, Tobias A1 - Laucht, Manfred A1 - Rietschel, Marcella T1 - Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence JF - Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man N2 - Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk. The externalizing disorders group had significantly lower NR3C1 methylation levels than the lifetime depressive disorder group (p = 0.009) and healthy controls (p = 0.001) This report of lower methylation levels in NR3C1 in externalizing disorders may indicate a mechanism through which the differential development of externalizing disorders as opposed to depressive disorders might occur. KW - Epigenetic KW - Glucocorticoid receptor KW - Methylation KW - Externalizing disorders KW - Adolescents Y1 - 2015 U6 - https://doi.org/10.1007/s10519-015-9721-y SN - 0001-8244 SN - 1573-3297 VL - 45 IS - 5 SP - 529 EP - 536 PB - Springer CY - New York ER -