abstract: Prior research has established associations between sleep duration and body mass index (BMI) scores and risk for obesity in middle childhood, but it is less clear whether other objectively- and subjectively-measured sleep indicators may be associated with BMI scores, weight status (e.g., obesity), and other estimates of weight and body fat such as waist circumference (WC) and percent body fat. Empirical studies have also demonstrated independent associations between broad self-regulation and sleep indicators and BMI scores, but no study to date has tested these factors in a model together and the extent to which associations between normative sleep problems, weight indicators, and effortful control (EC) may be explained by shared genetic or environmental influences. Data from a large longitudinal study of twins was used to test phenotypic associations between sleep problems at eight years and weight indicators at nine years, including whether EC at eight years moderates these associations. Additionally, multiple quantitative behavior genetic models were used to estimate unique and shared genetic and environmental covariances among normative sleep problems, weight indicators, and EC at eight years of age and whether additive genetic influence on weight in middle childhood differs by child weight status group. Phenotypic findings showed that greater sleep duration at eight years predicted greater decreases BMI at nine years of age for children with low levels of EC at eight years. Greater sleep midpoint variability at eight years predicted greater increases in percent body fat from eight to nine years of age for children with low EC at eight years. Behavior genetic findings showed greater environmental influences on parent-reported sleep duration and quality, as well as objective sleep midpoint variability. Similarly, associations between parent-reported sleep duration and sleep midpoint variability and other sleep indicators and EC were primarily accounted for by shared environmental factors. In contrast, there was high additive genetic influence on objective sleep quantity and quality, all weight indicators, and EC. Many of the associations between sleep indicators, sleep and weight indicators, and among weight indicators were entirely accounted for by shared additive genetic factors, suggesting that common, underlying sets of genes explain these relations. / Dissertation/Thesis / Doctoral Dissertation Psychology 2019

Aversion therapy has reemerged as a treatment for self-injurious behavior (SIB) but remains unpopular, as it is perceived to be unethical. The purpose of this mixed-methods sequential explanatory study was to investigate the effectiveness of positive therapy and aversion therapy in the treatment of twins with SIB as well as to understand the lived experiences of their caretakers regarding treatment ethics. The frameworks used included classical and operant conditioning as well as utilitarian ethics theory. Quantitative research questions focused on changes in SIB, aggressive and prosocial behaviors with treatment, while the qualitative research question focused on the perceptions of caretakers regarding treatment. The quantitative component used a case study design and archived data from 2 U.S.-based treatment centers. The qualitative component included essay-type questionnaires for family members and caretakers regarding perceptions of the different therapies. The quantitative data that was obtained measured different behaviors that were not comparable. The twin in aversion therapy demonstrated aggressive behaviors that decreased with treatment, while the twin in positive therapy demonstrated positive behaviors that showed little to no change. Caretaker and family reports were consistent with the quantitative data, and family members considered aversion therapy ethical because they perceived it to be effective in treating SIBs. They also perceived it as ethically preferable to the use of large amounts of medication. Findings suggest that aversion therapy may be effective and ethical. Implications for positive social include potential continued research on aversion therapy to enhance treatment outcomes for individuals with SIB, and possible changes in public perceptions of aversion therapies.

Although the rates of delinquent behavior have been decreasing since the 1990s, adolescent delinquent behavior continues to take a great toll on society as well as on perpetrators themselves. In this way, it is essential to understand the process of delinquency development. The current dissertation is comprised of three studies that analyzed the predictors and the development of delinquency using genetically-informed designs. The sample used for all studies comes from the Add Health dataset, a nationally-representative data on adolescents followed across 14 years. The first study modeled the longitudinal development of delinquency in three adolescent cohorts: early, middle, and late adolescence. The results showed significant heritability effects on delinquency, with varying estimates across cohorts. The longitudinal stability of delinquency was mostly driven by heritability, while changes were affected by nonshared environmental influences. The second study tested the GxE interaction between two dopaminergic polymorphisms (DRD4 7-repeat allele and DRD2 A1 allele) and parenting, operationalized by child abuse on the one negative extreme and maternal closeness on the other, in longitudinally predicting delinquent behaviors. Main effects of maternal closeness and childhood abuse on later delinquency were found. On the other hand, no significant interaction of DRD2 or DRD4 polymorphisms with either maternal closeness or childhood abuse were observed. The third study used a twin design to test whether neighborhood disadvantage has a genetic component and whether this might be explained by an individual’s IQ and self-control. The results showed substantial heritability of the neighborhoods the individuals moved into as adults. This was partly explained by IQ, as adolescents’ IQ predicted neighborhood disadvantage 14 years later.

Children with severe physical disabilities often do not have the capabilities for oral communication. Therefore, the vocabulary needs of nonspeaking children has been a subject of research in the area of augmentative communication for a number of years. The idea of allowing children with disabilities the opportunity for expression and communication is one not easily ignored. Obtaining vocabulary items, however, that are useful to nonspeaking disabled children that also meet normal language acquisition standards has been a concern. This study specifically addresses this concern by looking into the vocabulary issues of twins. The purpose of this research project is to verify that differences exist in the expressive vocabulary needs that are determined for a nonspeaking, cerebral-palsied twin and a speaking, able-bodied twin by a caregiver despite similar verbal environments.

Introduction—Bullying involvement is associated with many long-term adverse outcomes. Bullied children are at risk for internalizing disorders including anxiety, depression and suicidal behavior in childhood and adulthood. Bullies are also at risk for psychiatric disorders, specifically externalizing disorders. Bully victims—children who are both bullied and bullies—have a particularly poor prognosis, with a higher risk for internalizing and externalizing disorders. The purpose of this study is to study the epidemiology, risk of psychiatric disorders, and genetic and environmental influences of being bullied, a bully, and a bully victim—in the sample and individually in males and females. Methods—Twins (N=2,844, aged 8-17) from the Virginia Twin Study of Adolescent Behavioral Development and the Young Adult Follow-Up were used to study bullying involvement. Child and mother responses from three waves of data collection were used to determine bullying involvement status and to diagnose internalizing and externalizing disorders. The epidemiology of bullying involvement was examined. The odds ratios (OR) of being involved in bullying and having a psychiatric disorder were calculated. The twin methodology was used to estimate the genetic and environmental influences of bullying involvement. Results—In the sample, 14.56% were bullied, 17.33% were bullies, and 10.69% were bully victims. Males are more often involved in bullying, but females are more severely affected by their involvement. Bullied children are at a higher risk for internalizing disorders, especially young adult depression (OR 1.29). Bullies are at a higher risk for externalizing disorders, and depression (OR 1.72). Bully victims are at a higher risk for nearly every disorder tested. Bullying involvement is heritable, and being bullied has a dominance genetic component. The heritability of being bullied, a bully, and a bully victim is 48.12%, 54.81%, and 62.62% respectively. Conclusion—Individuals involved in bullying are at risk for serious and long-lasting psychiatric disorders. Interventions need to be developed that target each category of bullying involvement, and the specific disorders that these children are at risk for, while keeping in mind that their involvement is heritable.

Introduction. Callous-unemotional (CU) traits predict socially debilitating outcomes including Antisocial Personality Disorder and violent crime in adulthood. Despite significant research, the etiology of CU traits is not well understood. This dissertation incorporates genetic, physiological, neuroanatomical, and self-report measures to investigate the etiology of CU traits. Specifically, this project focuses on measures previously found to associate with impaired fear-processing observed in individuals high on CU. Brain morphometry for paralimbic regions of interest (ROIs) and electromyographic facial eyeblink reflex to startle and fear-potentiated startle probes were investigated as potential endophenotypes for CU traits. Methods. Two genetically informative (ages 9-20) twin samples (N=1696 individuals; 848 twin pairs) were used to estimate the changing heritable and environmental influences on CU over the age range of 9-20 using age-moderated biometric structural equation modeling (SEM). To determine potential endophenotypes, shared genetic variance with CU was examined for baseline and fear-potentiated startle reflex and morphometric measures of brain ROIs. Results. The heritability of CU increases over the ages of 9-20, from approximately 34% at age 9 to 47% at age 20. Therefore, environmental mechanisms for CU are most influential at younger ages. Although there were no significant associations after correction for multiple testing, there was some evidence to suggest potential positive associations between CU traits and baseline and fear-potentiated startle in younger (9-14) females. There was also evidence suggesting potential negative associations between CU traits and right anterior cingulate cortex thickness as well as right posterior cingulate cortex thickness in females only. There was no genetic covariance between CU and any of the examined physiological or neuroanatomical phenotypes. Discussion. These results suggest that middle childhood may be the most salient time for environmental interventions associated with preventing or ameliorating CU traits. Furthermore, these results suggest that the cingulate cortex may play a role in the development of CU traits, possibly in females specifically. The cingulate cortex may influence CU traits through its roles in emotional processing, learning, and memory. Larger samples will likely be needed to determine the genetic relationship between CU traits and the structural development of the cingulate cortex.

Non-stoichiometric barium titanate (BaTiO3) powder of TiO2-excess compositions has been investigated using both reducing sintering and acceptor-doping. Crystalline phases were analysed by XRD. Attention has been paid to the analysis of the corresponding sintered microstructure by adopting scanning and transmission electron microcopy. Reducing sintering was in the low oxygen partial pressure, so as to dominate the oxygen-deficient. According to the defect chemistry, the purpose of acceptor-doping was the same as reducing sintering. We look out for phenomena which may be indicative that oxygen vacancies generated by acceptor-doping and reducing sintering have resulted in the metastable retention of high temperature hexagonal-BaTiO3 to an ambient temperature. In the Mg-doped study investigated the possibility that Mg2+ substitutes on Ti4+ site rather than the Ba2+ site, as expected from the radii. According to the unknown phase was indexed a supercell of MgTiO3, that showed evidence of Mg2+ dissolves in BaTiO3 and occupies the Ba2+ site. To reduce in a hydrogen atmosphere was a high dark conductivity. The Ti3+ content was determined via colorimetry. Because of the defect chemistry led to oxygen-deficient h-BaTiO3, i.e.BaTi1-xTixO3-x/2. The observed volume expansion behavior under Ar-H2 atmosphere demonstrates the possibility of having various microstructures via control of oxygen partial pressure. The transformation matrix described the relation between the two reciprocal lattices of the twinning. Investigation of reciprocal lattices was shown that ordering oxygen deficient on the BaO3 layer in the twin boundary. There was evidence of XRD patterns and surface energy that explained more and more twins in the microstructure via control of the low oxygen partial pressure. According to this theory, lamellae twins were generated by oxygen-deficient. The hexagonal phase might be also expressed as the cubic BaTiO3 containing twin boundary at BaO3 planes every three layers. That demonstrates the possibility of hexagonal phase retention in BaTiO3 was oxygen vacancies.

Monozygotic (MZ) twins are currently used in epigenetic studies as one homogenous group. However, there are two MZ twin types: dichorionic (DC) and monochorionic (MC). We hypothesize that DCMZ twins are more similar epigenetically, compared to MCMZ twins, due to earlier zygote splitting, a higher degree of birth outcome similarity, or both. We recruited 220 newborn twins and obtained genome-wide DNA methylation profiles for 48 twins. Intraclass correlation coefficients (ICC) and linear mixed models were used to investigate the relationships between DNA methylation levels and chorionicity. DCMZ twins tended to have longer gestational age, larger birth weight, and smaller birth length discordance. DCMZ twins had more similar DNA methylation profiles than MCMZ twins (ICC=0.21 vs. 0.13), after adjusting for birth outcomes. Additionally, we identified 5,170 CpG sites with different DNA methylation levels between DCMZ and MCMZ twins. This study highlights the importance of incorporating chorionicity information in epigenetic twin studies.

Plasma lipid, lipoprotein and apolipoprotein levels are considered as important and well-established intermediate quantitative phenotypes of Cardiovascular Disease (CVD) risk. Both the mean values and the phenotypic variance vary over the human lifespan. However, it is not known whether there is a genetic basis for this age variability. For example, might different genes act, or different gene interactions occur, as a person ages? If so, how might this be influenced by both environment and phenotype? An understanding of traits at different ages will not only provide insight into the genetic components involved in CHD development, but may also identify additional genetic factors that predispose an individual or population to premature (and later-onset) CHD. By identifying genetic factors that account for variation in important intermediate traits (i.e. lipid levels), we hope to gain a better understanding of disease mechanisms and thus a better chance of developing clinical strategies for preventing or possibly treating abnormal lipid levels and, by association, CHD. The aim of this thesis was to better identify and explain the genetic basis of CHD by focusing on the use of lipid traits as intermediate quantitative phenotypes of CHD. First, phenotypic analyses using structural equation modeling were performed to estimate the relative importance of genetic and environmental factors, and also to investigate whether these traits are influenced by the same gene(s) across time or whether they are age-specific genetic effects. Then, genome-wide linkage analysis was performed to localize cardiovascular susceptibility loci. Finally, a small genome-wide association scan (GWAS) was performed on a subset of the data to identify the relevant variants, in particular those showing associations across time. Phenotypes and marker data were collected in two Australian samples: an adolescent and adult twin pair samples. The adult sample consisted of 1453 twin pairs (968 monozygotic and 485 dizygotic), measured for lipid traits. 415 adult twins provided blood on two to five occasions. The adolescent dataset consisted of 965 twin families (397 monozygotic and 568 dizygotic) measured longitudinally at ages twelve, fourteen and sixteen, and their siblings tested once for the same lipid variables. Results from both the adult and adolescent cohorts indicated that there is more than one genetic factor influencing total cholesterol, HDL, LDL and triglycerides over time (i.e. from different measurement occasions). Common environmental factors did not contribute to variances (except for HDL in adolescents). There were no sex differences in the heritabilities of these intermediate phenotypes. Non-shared environmental factors did not have significant long-term effects. Overall, these two cohorts confirmed that genetic variation contributes substantially to variation in these traits, and suggested there are changes in the genes affecting plasma lipid concentration at different periods of life. Thus, there are age-dependent gene effects influencing HDL, LDL, total cholesterol, or triglycerides at different ages. In the adult genome data, there were 485 adult dizygotic twin pairs typed on average 595 markers, at an average inter-marker distance of 5.0 cM. The genome-wide linkage analysis revealed evidence for linkage in the 7p13 region for triglycerides. Possible candidate genes included NPC1L1 and GSBS. Other regions of “suggestive” linkage identified were chromosome 4p13 (at 62 cM) and Xq26.2-28 (81 cM). Adolescent twins and their siblings from 760 families were typed for linkage using 16,781 markers spaced across the genome at an average distance of 6.25 cM. The adolescent data revealed evidence for linkage to region 6p24.3 for triglycerides (–log10p = 6.81; equivalent LOD = 6.13; p = 0.00000016) and to region 2q31.1 for HDL (–log10p = 3.22, equivalent LOD = 2.27; p = 0.00061). No obvious candidate gene is known in this 6p region. Possible candidate genes in the 2q region include LRP2 and ABCB11. A significant region of linkage was also found on 2q35 for LDL (–log10p = 5.59; equivalent LOD score = 4.53). Other interesting regions of linkage included chromosomes 1q32.1, 4p15.1, 5q13.2, 11p14.3 and 18q11.2. Thus, regions were identified by linkage analyses that are likely to harbour genetic risk factors for cardiovascular disease in the analysed Australian population: chromosomes 7p13 (in adults), 6p24 (adolescents), 2q31.1 and 2q35 (in adolescents). Other regions included 1q32.1, 4p15.1, 5q13.2, 11p14.3 and 18q11.2 in adolescents and chromosome 4p13 and Xq26.2–28 in adults. Genome-wide association results for adolescents showed significant evidence of association between total cholesterol at age 14 (p = 8.24x10-7) and rs10503840 on 8p21.1. Such association has not previously been reported. Evidence of differential association across time was also found between HDL and variant rs10492859, located in the intron of the CDH13 gene, consistent with earlier studies on larger datasets. Significant association (p = 2.25x10-6) was also found between rs10507266 on 12q24.21 in an intron of THRAP2, a gene involved in early development of heart and brain, with triglycerides at age 12. Evidence of association was also found between HDL across time and variant rs10492859 on 16q23. Several other “suggestive” potential loci associated with lipid traits at one time point as well as across time were also found. In conclusion, the work described in this thesis establishes the importance of age-specific genetic effects on plasma lipids and lipoproteins, and identifies several regions of highly significant genetic linkage with these phenotypes in either adolescence or adulthood. It is clear that, as well as cross-sectional studies to identify genes affecting CVD risk factors, longitudinal genetic linkage and association studies are needed to assess relative contributions to risk across the lifespan.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.