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 - 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 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Jennen-Steinmetz, Christine A1 - Hohm, Erika A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Baumeister, Sarah A1 - Plichta, Michael M. A1 - Esser, Günter A1 - Schmidt, Martin A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Early maternal care may counteract familial liability for psychopathology in the reward circuitry JF - Social Cognitive and Affective Neuroscience N2 - Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants’ previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development. KW - maternal care KW - ADHD KW - ventral striatum KW - fMRI KW - resilience KW - aggression Y1 - 2018 U6 - https://doi.org/10.1093/scan/nsy087 SN - 1749-5016 SN - 1749-5024 VL - 13 IS - 11 SP - 1191 EP - 1201 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Holz, Nathalie E. A1 - Boecker-Schlier, Regina A1 - Buchmann, Arlette F. A1 - Blomeyer, Dorothea A1 - Jennen-Steinmetz, Christine A1 - Baumeister, Sarah A1 - Plichta, Michael M. A1 - Cattrell, Anna A1 - Schumann, Gunter A1 - Esser, Günter A1 - Schmidt, Martin A1 - Buitelaar, Jan A1 - Meyer-Lindenberg, Andreas A1 - Banaschewski, Tobias A1 - Brandeis, Daniel A1 - Laucht, Manfred T1 - Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder JF - Frontiers in human neuroscience N2 - 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. KW - childhood adversity KW - conduct disorder KW - amygdala KW - ventral striatum KW - fMRI Y1 - 2016 U6 - https://doi.org/10.1093/scan/nsw120 SN - 1749-5016 SN - 1749-5024 VL - 12 IS - 2 SP - 261 EP - 272 PB - Oxford Univ. Press CY - Oxford 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 -