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Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopa

Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. For this purpose, we first determined the genomic organization of ITGA6, and placed the gene on chromosome 2q by high resolution radiation hybrid mapping. Heteroduplex analysis of PCR products containing the individual exons of ITGA6, followed by direct nucleotide sequencing, revealed that the proband was homozygous for a G-to-T transversion in the +1 position of intron 12. This mutation, 1856+1G-->T, affects an invariant base of the 5' donor splice site predicting aberrant splicing involving exon 12. The mutation was verified in the proband's DNA by restriction enzyme digestion which also confirmed that the parents were heterozygous carriers of this mutation. Altered expression of alpha6 integrin, which forms a heterodimer with the beta4 subunit at the dermal-epidermal junction, would explain fragility and blistering as a result of minor trauma to the skin.

Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in > 160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Item does not contain fulltext, We examined whether externalizing problem behaviors (hyperactivity-impulsivity, aggressiveness, and inattention) predict illicit drug use independently, or whether their associations with drug use are mediated through cigarette smoking. We used a prospective longitudinal design within the FinnTwin12-17 study among Finnish adolescents with baseline at age 12 and follow-up surveys at ages 14 and 17. Path models were conducted with Mplus and included 1992 boys and 2123 girls. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17. The predictors were: externalizing behaviors (hyperactivity-impulsivity, aggressiveness, and inattention) assessed by teachers and parents (age 12) and self-reported cigarette smoking (age 14). The findings differed across behavior studied. The association of hyperactivity-impulsivity with drug use was mostly mediated through earlier cigarette smoking. Concerning aggressiveness and inattention, the results were different among girls than boys. Among girls no significant mediation occurred, whereas among boys more consistent evidence on mediation was seen. Consistently in all models, the direct association of early cigarette smoking on drug use was strong and highly significant. We conclude that the associations of externalizing problem behaviors with illicit drug use are partially mediated through cigarette smoking. Although interventions targeting externalizing problem behaviors may protect adolescents from early onset smoking and subsequently experimenting with drugs, interventions to prevent cigarette smoking initiation are also important in reducing risk of later drug use.

Background: Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins. Methods: We used longitudinal data from the FinnTwin12-17 study with baseline at age 11-12 and follow-up at ages 14 and 171/2, including 4138 individuals. The outcome was self-reported ever use of cannabis or other illicit drugs at age 171/2. The potential predictors were measures reported by the twins, their parents or teachers. As individual factors we tested smoking, alcohol use, behavioral and emotional problems; as peer factors: number of smoking friends and acquaintances with drug experience; as family factors: parental substance use, socio-economic status and pre-natal exposure to nicotine. We used logistic regression models, controlling for twinship, age and sex, to compute odds ratios (OR) for each potential predictor. To adjust for within-family confounds, we conducted conditional logistic regressions among 246 twin pairs discordant for drug use. Results: 13.5% of subjects had initiated use of cannabis or other illicit drugs by age of 171/2. When adjusted for within-family confounds, smoking, drinking, and aggressiveness, as well as smoking and drug use among peers predicted use of illicit drugs. In the final regression model, the significant predictors were female sex, early smoking onset, drinking to intoxi

Item does not contain fulltext, Background: Animal research suggests a programming effect of prenatal stress in the fetal period, resulting in disruptions in behavioural and neuromotor development. Physiological changes that mediate these effects include alterations in the hypothalamic-pituitary-adrenal axis and in testosterone levels. This human study focuses on changes related to these physiological systems after prenatal stress exposure. Methods: We examined the potential effect of prenatal stress associated with the Chernobyl disaster in an ongoing genetic epidemiological study in Finland. One birth cohort of twins (n = 121 twin pairs) was exposed in utero to maternal stress, and their saliva cortisol and testosterone levels at age 14 were compared with twins (n = 157 twin pairs) born one year later. Results: Cortisol levels in both sexes and testosterone levels among females were significantly elevated after prenatal exposure to maternal stress from the second trimester onwards, compared to reference groups of non-exposed adolescents. Exposure explains 3% of variance (p < 0.05) in cortisol levels and 18% of variance in testosterone levels (p < 0.001). No significant differences were found for exposure from either first or third trimester onwards. Conclusion: Our results suggest that prenatal exposure to maternal stress in the second trimester of pregnancy may have resulted in prenatal programming of physiological systems relating to cortisol and testosterone levels.

Item does not contain fulltext, Background: Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins. Methods: We used longitudinal data from the FinnTwin 12-17 study with baseline at age 11-12 and follow-up at ages 14 and 171/2, including 4138 individuals. The outcome was self-reported ever use of cannabis or other illicit drugs at age 171/2. The potential predictors were measures reported by the twins, their parents or teachers. As individual factors we tested smoking, alcohol use, behavioral and emotional problems; as peer factors: number of smoking friends and acquaintances with drug experience; as family factors: parental substance use, socio-economic status and pre-natal exposure to nicotine. We used logistic regression models, controlling for twinship, age and sex, to compute odds ratios (OR) for each potential predictor. To adjust for within-family confounds, we conducted conditional logistic regressions among 246 twin pairs discordant for drug use. Results: 13.5% of subjects had initiated use of cannabis or other illicit drugs by age of 171/2. When adjusted for within-family confounds, smoking, drinking, and aggressiveness, as well as smoking and drug use among peers predicted use of illicit drugs. In the final regression model, the significant predictors were female sex, early smoking onset, drinking to intoxication, having smoking peers and acquaintances with drug experience, father's weekly drinking to intoxication, and aggressive behavior among boys. Smoking initiation by age of 12 was the most powerful predictor among individuals (OR = 26, p < 0.001) and within discordant pairs (OR = 22, p < 0.001). Conclusions: Early onset smoking is a powerful predictor for subsequent use of illicit drugs among Finnish adolescents, but the causal nature of this relationship needs to be clarified.

Objective: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. Method: Exposed (n = 232) and non-exposed Finnish twins (n = 572) were compared. A semi-structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. Results: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32-fold risk (95% CI: 1.13-4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM-III-R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06-5.7), and a 2.01-fold risk (95% CI: 1.14-3.52) of having attention deficit hyperactivity disorder symptoms. Conclusion: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms.

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Item does not contain fulltext, Objective: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. Method: Exposed (n = 232) and non-exposed Finnish twins (n = 572) were compared. A semi-structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. Results: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32-fold risk (95% CI: 1.13-4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM-III-R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06-5.7), and a 2.01-fold risk (95% CI: 1.14-3.52) of having attention deficit hyperactivity disorder symptoms. Conclusion: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms.

Item does not contain fulltext, The aim of the present study was to test the structure of the work-family interface measure, which was intended to take into account both the positive and negative spillover between work and family demands in both directions. In addition, the links among the types of work-family spillover and the subjects' general and domain-specific well-being were examined. The sample (n= 202) consisted of Finnish employees, aged 42, who had a spouse/partner. Confirmatory factor analyses indicated that a four-factor model, including negative work-to-family spillover, negative family-to-work spillover, positive work-to-family spillover, and positive family-to-work spillover, was superior compared to the other factor models examined. Path analysis showed, as hypothesized, that the negative work-to-family spillover was most strongly related to low well-being at work (job exhaustion) and next strongly to low general well-being (psychological distress), whereas the negative family-to-work spillover was associated with low well-being in the domain of family (marital dissatisfaction). Positive work-to-family spillover was positively related both to well-being at work and general well-being. Inconsistent with our expectations, positive family-to-work spillover was not directly related to any of the well-being indicators examined.

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