Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children

Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (Ncases = 612; Ncontrols = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.</p

The Casimir effect: from quantum to critical fluctuations

The Casimir effect in quantum electrodynamics (QED) is perhaps the best-known example of fluctuation-induced long-ranged force acting on objects (conducting plates) immersed in a fluctuating medium (quantum electromagnetic field in vacuum). A similar effect emerges in statistical physics, where the force acting, e.g., on colloidal particles immersed in a binary liquid mixture is affected by the classical thermal fluctuations occurring in the surrounding medium. The resulting Casimir-like force acquires universal features upon approaching a critical point of the medium and becomes long-ranged at criticality. In turn, this universality allows one to investigate theoretically the temperature dependence of the force via representative models and to stringently test the corresponding predictions in experiments. In contrast to QED, the Casimir force resulting from critical fluctuations can be easily tuned with respect to strength and sign by surface treatments and temperature control. We present some recent advances in the theoretical study of the universal properties of the critical Casimir force arising in thin films. The corresponding predictions compare very well with the experimental results obtained for wetting layers of various fluids. We discuss how the Casimir force between a colloidal particle and a planar wall immersed in a binary liquid mixture has been measured with femto-Newton accuracy, comparing these experimental results with the corresponding theoretical predictions.Comment: Talk delivered at the International Workshop "60 Years of Casimir Effect", Brasilia, 23-27 June 2008 (17 pages, 7 figures

Functional network topology of the right insula affects emotion dysregulation in hyperactive-impulsive attention-deficit/hyperactivity disorder

Contains fulltext : 236832.pdf (Publisher’s version ) (Open Access

Emotion dysregulation and integration of emotion-related brain networks affect intraindividual change in ADHD severity throughout late adolescence

Contains fulltext : 244227.pdf (Publisher’s version ) (Open Access

Chronic Stress and Adolescents' Mental Health:Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study

Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history. With Linear Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2 % boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the absence of a parental psychiatric history increased the risk of externalizing but not internalizing problems following chronic stress. Conversely, low basal cortisol combined with a substantial parental psychiatric history increased the risk of internalizing but not externalizing problems following chronic stress. Thus, parental psychiatric history moderated stress- cortisol interactions in predicting psychopathology, but in a different direction than hypothesized. We conclude that the premise that basal cortisol indicates context sensitivity may be too crude. Context sensitivity may not be a general trait but may depend on the nature of the context (e.g., type or duration of stress exposure) and on the outcome of interest (e.g., internalizing vs. externalizing problems). Although consistent across informants, our findings need replication

Executive function in children with Tourette syndrome and attention-deficit/hyperactivity disorder:Cross-disorder or unique impairments?

Contains fulltext : 217340.pdf (Publisher’s version ) (Closed access

ADHD symptoms across adolescence:the role of the family and school climate and the DRD4 and 5-HTTLPR genotype

We examined bidirectional relations between attention-deficit/hyperactivity disorder (ADHD) symptoms and family and school climate, and the possible role of DRD4 and/or 5-HTTLPR genotypes herein. Three-wave longitudinal data of 1860 adolescents (mean ages 11, 13.5, and 16 years) from the general population and clinic-referred cohort of TRacking Adolescents' Individual Lives Survey were used. Using a multigroup Random Intercept Cross-Lagged Panel Model, we tested between-person (i.e., stable trait levels) and within-person (i.e., causal processes) associations across ADHD symptoms, family and school climate, and the extent to which these depended on genotype. Findings indicated no influence of genotype. Results did show significant between-person differences (ADHD symptoms with family climate r = .38; and school climate r = .23, p values <.001), indicating that higher stable levels of ADHD symptoms were associated with a less favorable family and school climate. Regarding within-person causal processes, ADHD symptoms predicted a less favorable family climate in early adolescence (beta = .16, p <.01), while ADHD symptoms predicted a more favorable family climate in the later phase of adolescence (beta = - .11, p <.01), a finding which we explain by normative developmental changes during adolescence. Overall, this study showed that negative associations between ADHD symptoms and both family and school climate are largely explained by stable between-person differences. We recommend applying the Random Intercept Cross-Lagged Path Model to developmental data to tease stable associations and change processes apart

Parental rejection in early adolescence predicts a persistent ADHD symptom trajectory across adolescence

Despite a general decrease of attention-deficit/hyperactivity disorder (ADHD) symptoms during adolescence, these may persist in some individuals but not in others. Prior cross-sectional studies have shown that parenting style and their interaction with candidate genes are associated with ADHD symptoms. However, there is a lack of longitudinal research examining the independent and interactive effects of parenting and plasticity genes in predicting the course of attention-deficit/hyperactivity disorder (ADHD) symptoms across adolescence. Here, we investigated how children perceived their parents' parenting style (i.e., rejection, overprotection, and emotional warmth) at the age of 11, and their interaction with DRD4,MAOA, and 5-HTTLPR genotypes on parent-reported ADHD symptoms at three time points (mean ages 11.1, 13.4, and 16.2 years) in 1730 adolescents from the TRacking Adolescents' Individual Lives Survey (TRAILS). Growth Mixture Modeling in Mplus identified four ADHD symptom trajectories: low, moderate stable, high decreasing, and high persistent. Perceived parental rejection predicted class membership in the high persistent trajectory compared to the other classes (p < 0.001, odds ratios between 2.14 and 3.74). Gene-environment interactions were not significantly related to class membership. Our results indicate a role of perceived parental rejection in the persistence of ADHD symptoms. Perceived parental rejection should, therefore, be taken into consideration during prevention and treatment of ADHD in young adolescents

Polygenic risk scores for antisocial behavior in relation to amygdala morphology across an attention deficit hyperactivity disorder case-control sample with and without disruptive behavior

Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior association. We hypothesized that polygenic (risk) scores for antisocial and aggressive behaviors (ASB-PRS) would be related to amygdala morphology. Using the Broad Antisocial Behavior Consortium genome-wide association study (GWAS; mostly population based cohorts), we calculated ASB-PRS in the NeuroIMAGE I ADHD case-control sample with varying levels of DBD symptomatology (n=679 from 379 families, aged 7 - 29). We first investigated associations of several ASB-PRS p value thresholds with the presence of DBD symptoms and self-reported antisocial behavior (ASB) to determine the threshold for further analyses. This PRS was then related to amygdala volume and shape using regression and vertex-wise analyses. Our results showed associations of ASB-PRS with the presence of DBD symptoms, self-reported ASB, and left basolateral amygdala shape, independent of ADHD symptom severity and ADHD-PRS, with a relative outward displacement of the vertices. No associations of ASB-PRS, DBD symptoms or self-reported ASB with amygdala volume were found. Our results indicate that genetic risk for antisocial and aggressive behaviors is related to amygdala shape alterations, and point to genetic sharing across different DBD and ASB and aggression-related phenotypes as a spectrum of genetically related quantitative traits. Additionally, our findings support the utility of vertex-based shape analyses in genetic studies of ASB, aggression, and DBDs