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Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

Children who like to read and write tend to be better at it. This association is typically interpreted as enjoyment impacting engagement in literacy activities, which boosts literacy skills. We fitted direction-of-causation models to partial data of 3690 Finnish twins aged 12. Literacy skills were rated by the twins' teachers and literacy enjoyment by the twins themselves. A bivariate twin model showed substantial genetic influences on literacy skills (70%) and literacy enjoyment (35%). In both skills and enjoyment, shared-environmental influences explained about 20% in each. The best-fitting direction-of-causation model showed that skills impacted enjoyment, while the influence in the other direction was zero. The genetic influences on skills influenced enjoyment, likely via the skills[right arrow]enjoyment path. This indicates an active gene-environment correlation: children with an aptitude for good literacy skills are more likely to enjoy reading and seek out literacy activities. To a lesser extent, it was also the shared-environmental influences on children's skills that propagated to influence children's literacy enjoyment. Environmental influences that foster children's literacy skills (e.g., families and schools), also foster children's love for reading and writing. These findings underline the importance of nurturing children's literacy skills.

Abstract Background Evidence for substance use‐related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use‐related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods We conducted a population‐based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use‐related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use‐related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol‐related somatic disease, conviction for a substance‐related crime, and substance‐related death. Results Individuals with mild intellectual disability had a higher risk of any substance use‐related problem compared to the general population (HR, 1.81; 95% CI, 1.72–1.91), both in males (HR, 1.76; 95% CI, 1.65–1.89) and females (HR, 1.89; 95% CI, 1.74–2.05). The risks of substance use‐related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21–8.24). The associations were attenuated in the sibling comparison models. Conclusions Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use‐related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use‐related problems.

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.

Abstract Although rarely reported, bilateral loss of vision is a severe complication of childhood bacterial meningitis. We assessed its frequency in five prospective treatment trials performed in Europe, Latin America, and Angola in 1984–2017. Course of illness, follow-up findings, and child’s sight were recorded. Sight was examined at discharge, and conditions permitting, also at 1–3 months post-hospitalization and in Angola on hospital day 7. Experienced pediatricians diagnosed clinical blindness if the child did not make eye contact, did not blink or move the eyes, or remained unresponsive to bright light or movement of large objects before their eyes. Of 1515 patients, 351, 654, and 510 were from Finland, Latin America, and Angola, respectively. At discharge, blindness was observed in 0 (0%), 8 (1.2%), and 51 (10%) children, respectively. In Angola, 64 children appeared to be blind on day 7; 16 of these children died. Blindness found at discharge in Angola was not invariably irreversible; approximately 40% had restored the sight at follow-up visit. Clinical blindness rarely occurred in isolation and was usually associated with young age and poor general condition at hospital arrival. Various other serious sequelae were common among the survivors with clinical blindness.

Abstract Background Several risk factors for alcohol and other substance use disorders (SUDs) have been identified, but it is not well understood whether their associations with SUD are independent of each other. In particular, it is not well known, whether the associations between behavioral and affective factors and SUDs are independent of other risk factors. The incidence of SUDs peaks by young adulthood making epidemiological studies of SUDs in young adults informative. Methods In a comprehensive population-based survey of mental health in Finnish young adults (aged 21-35 years, n = 605), structured clinical interview (SCID-I) complemented by medical record data from all lifetime hospital and outpatient treatments were used to diagnose SUDs. We estimated the prevalences of lifetime DSM-IV SUDs, and investigated their associations with correlates from four domains representing: (1) behavioral and affective factors, (2) parental factors, (3) early initiation of substance use, and (4) educational factors. Independence of the association of behavioral and affective factors with SUD was investigated. Results Lifetime prevalences of abuse or dependence of any substance, alcohol, and any illicit substance were 14.2%, 13.1%, and 4.4%, respectively. Correlates from all four domains were associated with SUD. The associations between behavioral and affective factors (attention or behavior problems at school, aggression, anxiousness) and SUD were largely independent of other correlates, whereas only daily smoking and low education associated with SUD after adjustment for behavioral and affective factors. Conclusion Alcohol use disorders are common in Finnish young adults, whereas other SUDs are less common than in many other developed countries. Our cross-sectional analyses suggested that the association between behavioral and affective factors and SUD was only partly accounted for by other correlates, such as early initiation of substance use and parental alcohol problems. In contrast, associations between many other factors and SUD were non-significant when adjusted for behavioral and affective factors.

Genome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability. There is growing evidence that PRS may prove useful for early identification of those at increased risk for certain diseases. The current potential of PRS for alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high-risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of (1) alcohol dependence/alcohol problems, (2) alcohol consumption, and (3) risky behaviors with AUD and other substance use disorder (SUD) criteria. These PRSs explain ~2.5-3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. Calculations of area under the curve (AUC) show PRS provide only a slight improvement over a model with age, sex, and ancestral principal components as covariates. While individuals in the top 20, 10, and 5% of the PRS distribution had greater odds of having an AUD compared to the lower end of the continuum in both COGA and FT12, the point estimates at each threshold were statistically indistinguishable. Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis and opioid) SUD criteria. PRSs are associated with risk for SUD in independent samples. However, usefulness for identifying those at increased risk in their current form is modest, at best. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

The lower risk gambling guidelines (LRGG) represent an evidence-based collaborative effort to provide clear advice to people on the limits of safe gambling consumption. The guidelines are as follows: 1) Gamble no more than 1% of household income per month; and 2) Gamble no more than 4 days per month; and 3) Avoid regularly gambling at more than 2 types of games. In an online survey study (N = 778), we evaluated the feasibility and acceptability of the LRGG among different subpopulations in Finland. We found that the guidelines were generally evaluated positively as understandable, sensible, clear, and "just right" in terms of their content. There were some notable differences between subpopulations: Individuals who were at risk of gambling problems evaluated the LRGG more negatively than others, while professionals working in the field of gambling prevention were the most optimistic about the guidelines. Thus, increased level of potentially harmful gambling engagement was linked with a somewhat more pessimistic attitude towards the guidelines. On the other hand, those who had not gambled in the past year viewed the guidelines as too permissive compared with those who had gambled, or those working in gambling prevention. Overall, our results show clear differences of opinion between the various subpopulations, which appear to be associated with the individuals' level and nature of gambling experience. We conclude that the LRGG can likely be adopted into wider use in Finland. [ABSTRACT FROM AUTHOR]

Background: There is currently insufficient understanding of the health and behavior of children whose parents engage in criminal behavior. We examined associations between parental criminal convictions and wide range of offspring health, behavioral, and social outcomes by age 18 in a large, national sample, aiming to get a comprehensive picture of the risks among children of offending parents. Methods: We studied 1,013,385 individuals born in Sweden between 1987 and 1995, and their parents. Using data from several longitudinal nationwide registers, we investigated parental convictions and 85 offspring outcomes until the end of 2013, grouped into birth‐related conditions, psychiatric and somatic disorders, accidents and injuries, mortality, school achievement, violent victimization, and criminality. Cox proportional hazards regression and logistic regression models were used to examine the associations. The role of genetic factors in intergenerational associations was studied in children‐of‐siblings analyses. We also examined the co‐occurrence of multiple outcomes using Poisson regression. Results: A total of 223,319 (22.0%) individuals had one parent convicted and 31,241 (3.1%) had both parents convicted during the first 18 years of their life. The strongest associations were found between parental convictions and offspring behavioral problems, substance use disorders, poor school achievement, violent victimization, and criminality, with an approximately 2 to 2.5‐fold increased risk in children with one convicted parent and 3‐ to 4‐fold increased risk in children with two convicted parents. The risks were particularly elevated among children of incarcerated parents with a history of violent convictions. The associations appeared to be at least partly explained by genetic influences. Parental convictions were also associated with an increased likelihood of experiencing multiple outcomes. Conclusions: Our findings help to calibrate the risks of a wide range of adverse outcomes associated with parental convictions and may be used to guide prevention efforts and identify key areas for future research. [ABSTRACT FROM AUTHOR]

Introduction Population research indicates that smoking behaviors in Finland have varied over time by sex and birth cohort. Smoking behaviors are influenced by genes and the environment; like the behaviors themselves, these underlying influences are not necessarily stable over time and may be modifiable by national drug policy. Aims and Methods We utilized longitudinal mixed-effects models and causal–common–contingent twin models to evaluate sex and cohort effects on tobacco consumption and the underlying genetic and environmental variance components in a birth cohort sample of same-sex twins born in Finland between 1880 and 1957, assessed in 1975, 1981, 1990, and 2011. Results We identified significant main effects of age, sex, and cohort on quantity of cigarette consumption, as well as significant age × cohort and sex × cohort interactions. We also identified sex and cohort effects on the liability to initiate regular smoking and the magnitude of variation underlying quantity of cigarette consumption. That said, heritability and environmental contributions to both traits were not different between the four sex × cohort groups. Conclusions Our results indicate sex and cohort effects on the prevalence of smoking and its underlying variation. Our results on changing prevalence mirror existing population-level research in Finnish samples, but we did not identify differences in heritability found in other studies of cohort effects in tobacco use, potentially due to power issues. These results highlight the importance of considering age, cohort, and timing of policy changes when evaluating changes in substance consumption across time. Implications This study identifies sex and cohort effects influencing tobacco consumption in a sample of Finnish adult twins born between 1880 and 1957. Our results are in line with other population-level research in Finland and research on cohort effects influencing alcohol use in the same sample. Our results highlight the intertwining effects of age, cohort, sex, and substance policies on substance use. [ABSTRACT FROM AUTHOR]

Computerized game-based assessment (GBA) system for screening reading difficulties may provide substantial time and cost benefits over traditional paper-and-pencil assessment while providing means also to individually adapt learning content in educational games. To study the reliability and validity of a GBA system to identify struggling readers performing below a standard deviation from mean in paper-and-pencil test either in raw scores and grade-normative scores, a large-scale study with first to fourth grade students (N = 723) was conducted, where GBA was administrated as a group test by tablet devices. Overall, the results indicated that the GBA can be successfully used to identify students with reading difficulties with acceptable reliability. Although the reliability of the results were at a very good level overall, the identification was even better in the reading fluency than in reading accuracy and in terms of raw scores than in grade-normative scores. These findings are the first to demonstrate the promise of GBA in assessing reading skills reliably and in a cost-efficient manner in classrooms. Furthermore, the developed GBA is directly applicable to an educational game for successfully supporting reading development of learners with varying levels of reading skill.

Introduction Depression is twice as common in women as in men, especially in the young age group. Multiple factors may contribute to this gender difference. Growing attention is being focused on the role of sex hormones, including those of hormonal contraception (HC). Some recent studies have indicated a higher risk of depression among women using HC, although the results are inconclusive. Objectives The aim of this study is to examine the associations between the use of hormonal contraception and the risk of depression in childbearing age women. Methods The original cohorts for the study included all women aged 15-49 years with at least one redeemed prescriptions for HC in Finland in 2017 (n=294,356), and a 1:1 age-matched cohort of non-users. After exclusion of prevalent cases (n=35,102), all incident cases of depression (as recorded in the Care Register of Health Care and Register of Primary Health Care Visits) in 2018-2019 were identified (n=23,480), and a 4:1 age-matched control group (n=93,920) was selected from the above cohorts. Current use of HC in the 180 days before the event was compared in cases and controls, and associations with risk of depression were tested via conditional multivariate logistic regression models. Results During the follow-up, 23,480 incident cases of depression were identified. Current use (in the 180 days before the event) of HC (OR 0.82, 95% CI 0.79-0.85), in particular of estradiol- or ethinylestradiol-containing combined HC was associated with a lower risk of depression (OR 0.83, 95% CI 0.76–0.89; OR 0.74, 95% CI 0.71–0.78, respectively) compared to non-use of HC. The results remained significant (OR 0.87, 95% CI 0.81-0.95; and OR 0.77, 95% CI 0.73-0.81, respectively) after controlling for covariates (marital and socioeconomic status, education level, chronic diseases). Use of progestin-only contraception was not associated with altered risk of depression. Conclusions Use of HC in childbearing age women is not associated with increased risk of depression. Rather, the use of estradiol- or ethinylestradiol-containing HC is associated with a lower risk of depression. Disclosure of InterestNone Declared

Background. Giant cell arteritis (GCA) is an autoimmune vasculitis affecting medium- and large-sized arteries. Vascular inflammation may lead to narrowing of the arterial lumen, and acute occlusion may result in vision loss and stroke. The classical symptoms include headache, fever, and jaw claudication. However, there is an increasing recognition of atypical presentations. Case Presentation. We report a case of a 70-year-old woman presenting with fluctuating manic symptoms and confusion, in addition to headache and musculoskeletal pain. After diagnosis of GCA, treatment with corticosteroids gradually improved the somatic symptoms. Conclusion. Corticosteroids led to a temporary exacerbation of manic symptoms, which improved after 3 to 4 weeks of continuous treatment, indicating that the symptoms were most likely associated with GCA. The patient manifested with clinical features and a clinical course that has, to our knowledge, not been described or published before. Therefore, GCA may be an underdiagnosed disease in psychiatric populations and should be considered in case of atypical, new-onset psychiatric disorders in the elderly.