A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain.

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD. © 2007 Elsevier Inc. All rights reserved

The Stability of Problem Behavior Across the Preschool Years: An Empirical Approach in the General Population

This study examined the stability of internalizing and externalizing problems from age 1.5 to 6 years, while taking into account developmental changes in the presentation of problems. The study comprised a population-based cohort of 7,206 children (50.4 % boys). At ages 1.5, 3, and 6 years, mothers reported on problem behavior using the Child Behavior Checklist/1.5-5 (CBCL/1.5-5). At each age we performed latent profile analysis on the CBCL/1.5-5 scales. Latent transition analysis (LTA) was applied to study the stability of problem behavior. Profiles of problem behavior varied across ages. At each age, 82–87 % of the children did not have problems whereas approximately 2 % showed a profile of co-occurring internalizing and externalizing problems. This profile was more severe (with higher scores) at 6 years than at earlier ages. A predominantly internalizing profile only emerged at 6 years, while a profile with externalizing problems and emotional reactivity was present at each age. LTA showed that, based on profiles at 1.5 and 3 years, it was difficult to predict the type of profile at 6 years. Children with a profile of co-occurring internalizing and externalizing problems early in life were most likely to show problem behavior at 6 years. This study shows that the presentation of problem behavior changes across the preschool period and that heterotypic continuity of problems is very common among preschoolers. Children with co-occurring internalizing and externalizing problems were most likely to show persisting problems. The use of evidence-based treatment for these young children may prevent psychiatric problems across the life course

Violin varnishes: microstructure and nanomechanical analysis

The aim of the current work is twofold: to demonstrate the application of in situ non-invasive imaging by portable atomic force microscopy (AFM) on the surfaces of a violin and to integrate compositional and mechanical analysis at the nano scale level on model samples of varnished wood. These samples were prepared according to traditional recipes by an Italian lutemaker family well practised in the art. Samples of oil and spirit-based varnishes on maple wood, naturally and accelerated light aged, were studied. AFM was used to measure the nanomechanical properties of the model samples and established that the spirit-based varnish was stiffer than the oil-based. Synchrotron radiation micro- Fourier Transform Infra-red analysis of the layer structure revealed that stiffer spirit-based varnish showed less penetration into the wood than the oil-based. Further PeakForce Quantitative Nanomechanical Mapping (QNM) demonstrated a difference in adhesion values between the oil- and spirit-based sample

Heritability of attention problems in children II: longitudinal results from a study of twins age 3 to 12.

this paper we present data of large samples of twin families, with an equal number of girls and boys. The well-known gender difference with boys displaying more OA and AP was observed at each age. Even at the age of 3, boys display more OA problems than girls. Clinical studies have indicated that severe problem behavior can be identified in very young children (see for review, Campbell, 1995; Keenan & Wakschlag, 2000; Shaw, Owens, Giovannelli, & Winslow, 2001) and that the onset of ADHD is during the pre-school period (Barkley, Fisher, Edelbrock, & Smallish, 1990; Table 6 Top part includes percentages of total variances (diagonal) and covariances (off-diagonal) explained by additive genetic, genetic dominance, and unique environmental components based on best fitting models. Percentages for boys and girls are reported below and above diagonal, respectively. Lower part includes correlations calculated for additive genetic, genetic dominance, and unique environmental sources of variance between different ages. Correlations for boys and girls are reported below and above diagonal, respectively Relative proportions of variance and covariance BoysnGirls A% D% E% OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 50n41 73 79 75 22n33 17 13 14 28n26 10 8 11 AP 7 59 33n57 50 53 31 39n16 31 28 10 28n27 19 19 AP 10 86 31 41n48 47 6 51 31n25 32 8 18 28n27 21 AP 12 71 24 31 40n54 16 55 45 30n18 13 21 24 30n28 Correlations between different ages BoysnGirls ADE OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 1.00 .60 .66 .57 1.00 .30 .16 .20 1.00 .15 .12 .14 AP 7 .57 1.00 .62 .57 .41 1.00 .99 1.00 .15 1.00 .46 .41 AP 10 .68 .56 1.00 .61 .08 .94 1.00 1.00 .11 .42 1.00 .50 AP 12 .49 .42 .53 1.00 .20 .98 .99 1.00 .14 .45 .58 1.00 ..

Genetic and Environmental Contributions to Self-Reported Thoughts of Self-Harm and Suicide

Thoughts of self-harm and suicidal behavior are thought to be influenced by both genetics and environment. Molecular genetic studies are beginning to address the question of which genes may be involved and whether different genes may be expressed in men and women. We examined thoughts of self-harm and suicidal behavior in a large general population twin sample including male and female same- and opposite-sex twins. In this study, data on self-reported thoughts of self-harm and suicide were obtained from self-report questionnaires (Beck Depression Inventory and Youth or Adult Self Report forms) in 6,265 twin pairs (11,008 individuals) aged 11-90 (62% female) from the Netherlands Twin Registry. Liability threshold models were compared including sex and age (linear and quadratic) effects. Models were compared using measures of parsimony to calculate the simplest model to the data. A model with additive genetic and unique environmental contributions fitted the data for both males and females. There were no qualitative sex differences, but the relative contributions differed between men and women. Heritability was higher in women (0.74, 95% CI 0.65-0.81) than men (0.45, 95% CI 0.28-0.61). The remaining variance was accounted for by environmental influence unique to an individual. These results suggest contributions from additive genetic factors to self-reported thoughts of self-harm and suicide and support the continued study of both molecular genetic and individual-specific environmental risk factors. © 2011 Wiley Periodicals, Inc