In 1859, Ludvig Dahl, a Norwegian alienist, wrote a rarely referenced book entitled “Contribution to The Knowledge of Insanity.” In it, he describes a highly innovative psychiatric genetics research ...project with severable notable features. First, while the vast majority of 19th century psychiatric genetic studies were based on asylum hospital records, Dahl did field work to find cases of mental illness in certain defined areas within Norway, using census data, key‐informants, record reviews, and personal interviews especially of suspected affected individuals. Second, for the first time in the history of psychiatric genetics, and perhaps more broadly in medical genetics, Dahl studied and graphed extensive pedigrees covering up to seven generations demonstrating a high density of psychiatric illness. Third, he proposed and conducted the first controlled investigation of familial aggregation of insanity. A 126 member 5‐generation pedigree that he studied contained 8 individuals with confirmed insanity compared to 16 cases in the remaining 2,974 individuals in the Parish, a relative risk of nearly 12. Dahl also noted the co‐segregation within pedigrees of mental handicap, deaf‐mutism, and insanity. He evaluated familial‐environmental sources of familial aggregation and noted, among nonpsychotic family members in his pedigrees, personalities that might reflect a “disposition” to insanity.
Background and aims
Studies have indicated that maternal prenatal substance use may be associated with offspring attention deficit hyperactivity disorder (ADHD) via intrauterine effects. We measured ...associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms accounting for shared familial factors.
Design
First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner's substance use). The results were meta‐analysed across the cohorts. Secondly, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for smoking, alcohol and coffee consumption were regressed against ADHD symptoms. We triangulated the results across the two approaches to infer causality.
Setting
We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway.
Participants
Phenotype data available for children were: NALSPAC = 5455–7751; NGENR = 1537–3119; NMOBA = 28 053–42 206. Genotype data available for mothers was: NALSPAC = 7074; NMOBA = 14 583.
Measurements
A measure of offspring ADHD symptoms at age 7–8 years was derived by dichotomizing scores from questionnaires and parental self‐reported prenatal substance use was measured at the second pregnancy trimester.
Findings
The pooled estimate for maternal prenatal substance use showed an association with total ADHD symptoms odds ratio (OR)SMOKING = 1.11, 95% confidence interval (CI) = 1.00–1.23; ORALCOHOL = 1.27, 95% CI = 1.08–1.49; ORCAFFEINE = 1.05, 95% CI = 1.00–1.11, while not for fathers (ORSMOKING = 1.03, 95% CI = 0.95–1.13; ORALCOHOL = 0.83, 95% CI = 0.47–1.48; ORCAFFEINE = 1.02, 95% CI = 0.97–1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD symptoms in MoBa). The PRS analyses were inconclusive for an association in ALSPAC or MoBa.
Conclusions
There appears to be no causal intrauterine effect of maternal prenatal substance use on offspring attention deficit hyperactivity disorder symptoms.
Background
Prenatal exposure to maternal adverse life events has been associated with offspring ADHD, but the role of familial confounding is unclear. We aimed to clarify if adverse life events ...during pregnancy are related to ADHD symptoms in offspring, taking shared familial factors into account.
Method
Data were collected on 34,751 children (including 6,427 siblings) participating in the population‐based Norwegian Mother and Child Cohort Study. During pregnancy, mothers reported whether they had experienced specific life events. We assessed ADHD symptoms in five‐year‐old children with the Conners’ Parent Rating Scale–Revised: short form. We modeled the associations between life events and mean ADHD scores with ordinary linear regression in the full cohort, and with fixed‐effect linear regression in sibling comparisons to adjust for familial confounding.
Results
Children exposed to adverse life events had higher ADHD scores at age 5, with the strongest effect observed for financial problems (mean differences 0.10 95% CI: 0.09, 0.11 in adjusted model), and the weakest for having lost someone close (0.02 95% CI 0.01, 0.04 in adjusted model). Comparing exposure‐discordant siblings resulted in attenuated estimates that were no longer statistically significant (e.g. mean difference for financial problems −0.03 95% CI −0.07, 0.02). ADHD scores increased if the mother had experienced the event as painful or difficult, and with the number of events, whereas sibling‐comparison analyses resulted in estimates attenuated toward the null.
Conclusions
These results suggest that the association between adverse life events during pregnancy and offspring ADHD symptoms is largely explained by familial factors.
Do associations between maternal anxiety symptoms and offspring mental health remain after comparing differentially exposed siblings? Participants were 17,724 offspring siblings and 11,553 mothers ...from the Norwegian Mother and Child Cohort study. Mothers reported anxiety and depressive symptoms at 30 weeks’ gestation, and 0.5, 1.5, 3, and 5 years postpartum. Child internalizing and externalizing problems were assessed at ages 1.5, 3, and 5, and modeled using multilevel analyses with repeated measures nested within siblings, nested within mothers. Maternal pre‐ and postnatal anxiety were no longer associated with child internalizing or externalizing problems after adjusting for maternal depression and familial confounding. Maternal anxiety when the children were in preschool age, however, remained significantly associated with child internalizing but not externalizing problems.
Background
Delays and loss of early‐emerging social‐communication skills are often discussed as unique to autism. However, most studies of regression have relied on retrospective recall and clinical ...samples. Here, we examine attainment and loss of social‐communication skills in the population‐based Norwegian Mother, Father and Child Cohort Study (MoBa).
Methods
Mothers rated their child's attainment of 10 early‐emerging social‐communication skills at ages 18 and 36 months (N = 40,613, 50.9% male). Prospectively reported loss was defined as skill presence at 18 months but absence at 36 months. At 36 months, mothers also recalled whether the child had lost social‐communication skills. The Norwegian Patient Registry was used to capture diagnoses of Autism Spectrum Disorder (autism) and other neurodevelopmental disabilities (NDDs).
Results
Delay in at least one skill was observed in 14% of the sample and loss in 5.4%. Recalled loss of social‐communication skills was rare (0.86%) and showed low convergence with prospectively reported loss. Delay and especially loss were associated with elevated odds of an autism diagnosis (n = 383) versus no autism diagnosis (n = 40,230; ≥3 skills delayed: OR = 7.094.15,12.11; ≥3 skills lost: OR = 30.6617.30,54.33). They were also associated with an increased likelihood of autism compared to some other NDDs. Delay (relative risk RR = 4.162.08, 8.33) and loss (RR = 10.003.70, 25.00) associated with increased likelihood of autism versus ADHD, and loss (RR = 4.351.28,14.29), but not delay (RR = 2.000.78,5.26), associated with increased likelihood of autism compared to language disability. Conversely, delay conferred decreased likelihood of autism versus intellectual disability (RR = 0.110.06,0.21), and loss was not reliably associated with likelihood of autism versus intellectual disability (RR = 1.890.44,8.33).
Conclusions
This population‐based study suggests that loss of early social communication skills is more common than studies using retrospective reports have indicated and is observed across several NDD diagnoses (not just autism). Nevertheless, most children with NDD diagnoses showed no reported delay or loss in these prospectively measured skills.
Background and Aims
Individual differences in DSM‐IV personality disorders (PDs) are associated with increased prevalence of substance use disorders. Our aims were to determine which combination of ...PDs trait scores best predict cannabis use (CU) and cannabis use disorder (CUD), and to estimate the size and significance of genetic and environmental risks in PD traits shared with CU and CUD.
Design
Linear mixed‐effects models were used to identify PD traits for inclusion in twin analyses to explore the genetic and environmental associations between the traits and cannabis use.
Setting
Cross‐sectional data were obtained from Norwegian adult twins in a face‐to‐face interview in 1999–2004 as part of a population‐based study of mental health.
Participants
Subjects were 1419 twins (μage = 28.2 years, range = 19–36) from the Norwegian Institute of Public Health Twin Panel with complete PD and cannabis data.
Measurements
PD traits were assessed using DSM‐IV criteria. Life‐time CU and CUD were based on DSM‐IV abuse and dependence criteria, including withdrawal and craving.
Findings
After adjusting for age and sex, antisocial β = 0.23, 95% confidence interval (CI) = 0.19–0.28 and borderline PDs (β = 0.20, 95% CI = 0.14–0.26) were associated strongly with CU. Antisocial (β = 0.26, 95% CI = 0.21–0.31) and borderline PDs (β = 0.12, 95% CI = 0.06–0.18) were also linked strongly to CUD. Genetic risks in antisocial and borderline PD traits explained 32–60% of the total variance in CU and CUD. Dependent and avoidant PDs explained 11 and 16% of the total variance in CU and CUD, respectively.
Conclusions
Individual differences in the liability to cannabis use and cannabis use disorder appear to be linked to genetic risks correlated with antisocial and borderline personality disorder traits.
Sleep and depression are interlinked throughout the lifespan, but very few studies have examined the directionality of the sleep–depression link in children. The aim of the current study was to ...prospectively examine the bidirectional association between sleep problems and internalizing problems and depressive symptoms in toddlers and children aged 1.5 and 8 years. Data stem from the large ongoing population‐based longitudinal study, the Norwegian Mother, Father and Child Cohort Study, recruited from October 1999 to July 2009. A total of 35,075 children were included. Information on sleep duration, nocturnal awakenings and internalizing problems (Child Behaviour Checklist) was provided by the mothers at 1.5 years, whereas data on sleep duration and depressive symptoms (Short Mood and Feelings Questionnaire) were provided by the mothers when the children were 8 years old. Odds ratios (ORs) were calculated using logistic regression analyses. After accounting for previous internalizing problems, short sleep duration (≤10 hr) and frequent (≥3) nightly awakenings at 1.5 years predicted the development of depressive symptoms at 8 years of age (adjusted OR = 1.28; 95% confidence interval CI 1.08–1.51, and adjusted OR = 1.27, 95% CI 1.08–1.50, respectively). Also, internalizing problems at 1.5 years predicted onset of later short sleep duration (adjusted OR = 1.83, 95% CI 1.32–2.54) after accounting for early sleep problems. This prospective study demonstrated a bidirectional association between sleep and internalizing/depressive symptoms from toddlerhood to middle childhood. Intervention studies are needed to examine whether targeting either of these problems at this early age may prevent onset of the other.
Background
Mood and anxiety disorders account for a large share of the global burden of disability. Some studies suggest that early signs may emerge already in childhood. However, there is a lack of ...well‐powered, prospective studies investigating how and when childhood mental traits and trajectories relate to adolescent mood and anxiety disorders.
Methods
We here examine cross‐sectional and longitudinal association between maternally reported temperamental traits, emotional and behavioral problems in childhood (0.5–8 years) and clinical diagnosis of mood or anxiety (“emotional”) disorders in adolescence (10–18 years), using the prospective Norwegian Mother, Father and Child Cohort Study (MoBa) of 110,367 children.
Results
Logistic regression analyses showed consistent and increasing associations between childhood negative emotionality, behavioral and emotional problems and adolescent diagnosis of emotional disorders, present from 6 months of age (negative emotionality). Latent profile analysis incorporating latent growth models identified five developmental profiles of emotional and behavioral problems. A profile of early increasing behavioral and emotional problems with combined symptoms at 8 years (1.3% of sample) was the profile most strongly associated with emotional disorders in adolescence (OR vs. reference: 5.00, 95% CI: 3.70–6.30).
Conclusions
We found a consistent and increasing association between negative emotionality, behavioral and emotional problems in early to middle childhood and mood and anxiety disorders in adolescence. A developmental profile coherent with early and increasing disruptive mood dysregulation across childhood was the profile strongest associated with adolescent emotional disorders. Our results highlight the importance of early emotional dysregulation and childhood as a formative period in the development of adolescent mood and anxiety disorders, supporting potential for prevention and early intervention initiatives.
Background
Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism) and schizophrenia are highly heritable neurodevelopmental disorders, affecting the lives of many ...individuals. It is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls.
Methods
Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a subsample of 15 205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother‐reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18 months, 3, 5 and 8 years. Linear regression models in a multigroup framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, using sex as a grouping variable.
Results
Before the age of 2, the ADHD PRS was robustly associated with hyperactivity and inattention, with increasing strength up to 8 years, and with language difficulties at age 5 and 8. The autism PRS was robustly associated with language difficulties at 18 months, motor difficulties at 36 months, and hyperactivity and inattention at 8 years. We did not identify robust associations for the schizophrenia PRS. In general, the PRS associations were similar in boys and girls. The association between ADHD PRS and hyperactivity at 18 months was, however, stronger in boys.
Conclusions
Polygenic risk for autism and ADHD in the general population manifests early in childhood and broadly across behavioral measures of neurodevelopmental traits.
Psychotic-like experiences (PLE) have been associated with the subsequent emergence of psychotic disorders as well as several other domains of psychopathology. In this twin study, we estimated the ...genetic and environmental correlations between PLE and 10 personality disorders (PD).
Diagnoses of 10 PDs according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and PLE from the Composite International Diagnostic Interview (CIDI) were retrieved for 2793 young adult twins from the Norwegian Twin Registry. Risk for having a PD and PLEs was modeled using item response theory. Biometric twin models were fitted to estimate the genetic and environmental correlations between PDs and PLEs. Co-twin control analysis was performed to estimate additional within-family risk for PLEs when having a PD.
Phenotypic overlap between PDs and PLEs ranged from 14% to 44% in males and from 11% to 39% in females, with the highest overlap for borderline PD in both sexes. In general, we found higher genetic correlations (r = 0.14-0.72) than environmental correlations (r = 0.06-0.28) between PDs and PLEs. The highest genetic correlations between PLE and PDs were found for borderline (r = 0.72), paranoid (r = 0.56), schizotypal (r = 0.56) and antisocial PD (r = 0.49).
We found that the co-occurrence between PDs and PLE is the best explained by shared genetic determinants, with minor contributions from environmental factors. Interestingly, borderline PD was highly genetically correlated with PLE, warranting molecular genetic studies of this association.
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