Robust data-driven identification of risk factors and their interactions : A simulation and a study of parental and demographic risk factors for schizophrenia

Objectives Few interactions between risk factors for schizophrenia have been replicated, but fitting all such interactions is difficult due to high-dimensionality. Our aims are to examine significant main and interaction effects for schizophrenia and the performance of our approach using simulated data. Methods We apply the machine learning technique elastic net to a high-dimensional logistic regression model to produce a sparse set of predictors, and then assess the significance of odds ratios (OR) with Bonferroni-corrected p-values and confidence intervals (CI). We introduce a simulation model that resembles a Finnish nested case-control study of schizophrenia which uses national registers to identify cases (n = 1,468) and controls (n = 2,975). The predictors include nine sociodemographic factors and all interactions (31 predictors). Results In the simulation, interactions with OR = 3 and prevalence = 4% were identified with = 80% power. None of the studied interactions were significantly associated with schizophrenia, but main effects of parental psychosis (OR = 5.2, CI 2.9-9.7; p = 35 (1.3, 1.004-1.6; p = .04) were significant. Conclusions We have provided an analytic pipeline for data-driven identification of main and interaction effects in case-control data. We identified highly replicated main effects for schizophrenia, but no interactions.Peer reviewe

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case–control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82–1.18, p = 0.84) or as a categorical variable (25(OH)D 50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78–1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders

Parental psychological problems were associated with higher screen time and the use of mature-rated media in children

Publisher Copyright: © 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Aim: Parents’ psychological problems may affect children's screen time, but research has been scarce. We examined the association between parental psychological problems and children's screen media behaviours in a nationally representative sample. Methods: The participants were from the Adolescent Brain Cognitive Development study, recruited by probability sampling from the USA population. Children reported their use of TV, videos, video games, social media and mature-rated media. The parents (85% mothers) reported psychological problems using the Adult Self-Report questionnaire. Results: In 10,650 children (5112 girls, 5538 boys) aged 9.9 ± 0.6 years, the presence of parental psychological problems was associated with children spending more daily time on screen media and with meeting the recommendation of ≤2 daily hours less often than children whose parents did not have psychological problems. Parental psychological problems were associated with children's TV watching, video watching and gaming but not with using social media. Parental internalising problems were associated with children watching mature-rated movies (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.00, 1.30) and playing mature-rated games (OR = 1.27, 95% CI = 1.11, 1.45). Conclusion: Presence of parental psychological problems is associated with higher screen time and use of mature-rated media in children. This cross-sectional study was not able to examine causal associations.Peer reviewe

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case–control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82–1.18, p = 0.84) or as a categorical variable (25(OH)D 50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78–1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders

Prenatal Maternal Smoking and Tourette Syndrome: A Nationwide Register Study

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Prenatal Cotinine Levels and ADHD Among Offspring

OBJECTIVES: An association between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) has been shown across several studies based on self-reports. No previous studies have investigated the association of nicotine exposure measured by cotinine levels during pregnancy and offspring ADHD. METHODS: In this population-based study, 1079 patients born between 1998 and 1999 and diagnosed with ADHD according to the International Classification of Diseases and 1079 matched controls were identified from Finnish nationwide registers. Maternal cotinine levels were measured by using quantitative immunoassays from maternal serum specimens collected during the first and second trimesters of pregnancy and archived in the national biobank. RESULTS: There was a significant association between increasing log-transformed maternal cotinine levels and offspring ADHD. The odds ratio was 1.09 (95% confidence interval [CI] 1.06-1.12) when adjusting for maternal socioeconomic status, maternal age, maternal psychopathology, paternal age, paternal psychopathology, and child's birth weight for gestational age. In the categorical analyses with cotinine levels in 3 groups, heavy nicotine exposure (cotinine level >50 ng/mL) was associated with offspring ADHD, with an odds ratio of 2.21 (95% CI 1.63-2.99) in the adjusted analyses. Analyses by deciles of cotinine levels revealed that the adjusted odds for offspring ADHD in the highest decile was 3.34 (95% CI 2.02-5.52). CONCLUSIONS: The study reveals an association with and a dose-response relationship between nicotine exposure during pregnancy and offspring ADHD. Future studies incorporating maternal smoking and environmental, genetic, and epigenetic factors are warranted.Peer reviewe

Register-based study of the incidence, comorbidities and demographics of obsessive-compulsive disorder in specialist healthcare

BackgroundIncidence of obsessive-compulsive disorder (OCD) has been suspected to increase but nationwide epidemiological studies are limited. This study aims to examine sex-specific incidence time trends and characterize psychiatric and neurodevelopmental comorbidities and sociodemographic risk factors of OCD in specialist healthcare in Finland.MethodsA nationwide register-based study using data from four Finnish registers identified 3372 OCD cases and 13,372 matched controls (1:4). Cumulative incidence in subjects born between 1987 and 2001 was estimated at ages of 10, 15, 20 and 23 years. Conditional logistic regression was used to examine the sociodemographic factors.ResultsThe cumulative incidence of OCD was 0.4% by age 23. Incidence by age 15 among three cohorts increased from 12.4 to 23.7 /10000 live born males and 8.5 to 28.0 /10000 live born females. 73% of the sample had a comorbid condition. Males were significantly more comorbid with psychotic and developmental disorders; females were more comorbid with depressive and anxiety disorders (p ConclusionsThese findings suggest that incidence of treated OCD in specialist healthcare has increased. The reason may be increased awareness and rate of referrals but a true increase cannot be ruled out. Further research on risk factors of OCD is warranted.</div

Maternal Vitamin D Levels and the Risk of Offspring Attention-Deficit/Hyperactivity Disorder

Objective: Recent evidence has highlighted the importance of vitamin D in the development of the central nervous system. Some studies have shown an association between maternal vitamin D deficiency during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) symptoms based on parent or teacher ratings. There are no previous studies on early pregnancy 25-hydroxyvitamin D [25(OH)D] levels and the risk of diagnosed offspring ADHD. Our aim was to examine maternal 25(OH)D levels in early pregnancy and offspring ADHD. Method: In this nationwide population-based case-control study, 1,067 ADHD cases (born between 1998 and 1999 and diagnosed according to the International Classification of Diseases) and 1,067 matched controls were identified from Finnish registers. Maternal 25(OH)D levels were measured using quantitative immunoassay from maternal sera, collected during the first trimester and archived in the national biobank. Conditional logistic regression was used to examine the association between maternal 25(OH)D and offspring ADHD. Results: There was a significant association between decreasing log-transformed maternal 25(OH)D levels and offspring ADHD both in the unadjusted analyses (odds ratio 1.65; 95% CI 1.33-2.05; p <.001) and in the analyses adjusting for maternal socioeconomic status and age (odds ratio 1.45; 95% CI 1.15-1.81; p = .002). Analyses by quintiles of maternal 25(OH)D levels in the lowest versus highest quintile revealed an adjusted odds ratio for offspring ADHD of 1.53 (95% CI 1.11-2.12; p = .010). Conclusion: This study demonstrated an association between low maternal 25(OH)D during pregnancy and an elevated risk for offspring ADHD. If replicated in independent samples, this finding may have significant public health implications.Peer reviewe