ORCID Profile
0000-0002-6218-0428
Current Organisations
Worcester Polytechnic Institute
,
Arkin
,
Amsterdam UMC location AMC
,
Levvel
,
Children's Health Queensland Hospital and Health Service
,
University of Queensland
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Sociological Methodology and Research Methods | Sociology | Applied Sociology, Program Evaluation and Social Impact Assessment | Causes and Prevention of Crime
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge through Studies of Human Society | Families and Family Services | Crime Prevention |
Related Links
Publications
Heritability of self-reported phobic fear
Publisher: Springer Science and Business Media LLC
Date: 12-12-2008
Heritability of Anxious-Depressive and Withdrawn Behavior: Age-Related Changes During Adolescence
Publisher: Elsevier BV
Date: 03-2010
Meta-analysis of genome-wide association studies of anxiety disorders (vol 21, pg 1391, 2016)
Publisher: Springer Science and Business Media LLC
Date: 09-02-2016
DOI: 10.1038/MP.2016.11
The value of polygenic analyses in psychiatry
Publisher: Wiley
Date: 19-01-2018
DOI: 10.1002/WPS.20480
Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood: Genome-Wide Complex Trait Analysis
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JAAC.2015.06.004
Abstract: Genetic factors contribute to in idual differences in behavior problems. In children, genome-wide association studies (GWAS) have yielded the first suggestive results when aiming to identify genetic variants that explain heritability, but the proportion of genetic variance that can be attributed to common single nucleotide polymorphisms (SNPs) remains to be determined, as only a few studies have estimated SNP heritability, with erging results. Genomic-relationship-matrix restricted maximum likelihood (GREML) as implemented in the software Genome-Wide Complex Trait Analysis (GCTA) was used to estimate SNP heritability (SNP h(2)) for multiple phenotypes within 4 broad domains of children's behavioral problems (attention-deficit/hyperactivity symptoms, internalizing, externalizing, and pervasive developmental problems) and cognitive function. We combined phenotype and genotype data from 2 independent, population-based Dutch cohorts, yielding a total number of 1,495 to 3,175 of 3-, 7-, and 9-year-old children. Significant SNP heritability estimates were found for attention-deficit/hyperactivity symptoms (SNP h(2) = 0.37-0.71), externalizing problems (SNP h(2) = 0.44), and total problems (SNP h(2) = 0.18), rated by mother or teacher. Sensitivity analyses with exclusion of extreme cases and quantile normalization of the phenotype data decreased SNP h(2) as expected under genetic inheritance, but they remained statistically significant for most phenotypes. We provide evidence of the influence of common SNPs on child behavior problems in an ethnically homogenous s le. These results support the continuation of large GWAS collaborative efforts to unravel the genetic basis of complex child behaviors.
Risk factors for parental psychopathology: a study in families with children or adolescents with psychopathology
Publisher: Springer Science and Business Media LLC
Date: 11-04-2018
Research Review: Polygenic methods and their application to psychiatric traits.
Publisher: Wiley
Date: 08-2014
DOI: 10.1111/JCPP.12295
Abstract: Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. S le sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. Increasing the s le size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as s le sizes increase and as s le resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors.
Asset price dynamics with heterogeneous beliefs and local network interactions
Publisher: Elsevier BV
Date: 12-2013
The Val66Met polymorphism of the BDNF gene in anorexia nervosa: New data and a meta-analysis
Publisher: Informa UK Limited
Date: 21-09-2011
DOI: 10.3109/15622975.2011.605470
Abstract: The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and family-based studies testing this SNP in AN, and combined the results in a meta-analysis. The results of the case-control study were non-significant. For the meta-analysis, nine studies were identified (ncases = 2,767 ncontrols = 3,322, ntrios = 53) and included. Primarily, the analyses indicated an association with OR of 1.11 (P = 0.024) in the allelic contrast, and OR of 1.14 (P = 0.025) for the dominant effect of the Met allele. However, additional analyses revealed that the first published study (from those included in the meta-analysis) overly influenced the pooled effect size (possibly due to a phenomenon known as a winner's curse). When this case-control study was replaced by a trio study (ntrios = 293) performed on a largely overlapping s le, the effect size became smaller and non-significant, both for the allelic contrast (OR = 1.07, P = 0.156) and the dominant effect (OR = 1.07, P = 0.319). The quality of included studies was good and there was no significant heterogeneity across the effect sizes. Our analyses indicate that the BDNF Val66Met variant is not associated with AN at detectable levels.
Nonsymptomatic generalized epilepsy in children younger than six years: Excellent prognosis, but classification should be reconsidered after follow-up: The Dutch Study of Epilepsy in Childhood
Publisher: Wiley
Date: 07-2002
DOI: 10.1046/J.1528-1157.2002.72601.X
Abstract: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy. Of the cohort of the Dutch Study of Epilepsy in Childhood (n = 466), all children younger than 6 years with a diagnosis of idiopathic (IGE) or cryptogenic (CGE) generalized epilepsy either at intake (n = 108) and/or after 2 years of follow-up (n = 102) were included. The number of reclassifications after 2 years was determined, and the reasons for reclassification were analyzed. All children receiving a diagnosis of IGE or CGE at 2 years were followed up for 5 years to study their outcome in terms of terminal remission (TR). Data on their level of intellectual functioning were collected at the start of this analysis. The epilepsy syndrome was reclassified in 17 children. In 14 of them, the seizure type also was reclassified, and in three, the course of the epilepsy determined the new epilepsy type. Two other children had a reclassification of their seizure types without a change of the epilepsy type. Many children were categorized as having IGE not otherwise specified. In all probability, this is a heterogeneous group, containing patients with various epilepsy syndromes, with generalized tonic-clonic seizures as a common hallmark. Of the 102 children with IGE or CGE at 2 years of follow-up, 75% had a TR of >6 months after 2 years, and 85% a TR of >or=1 year after 5 years. In a fair proportion of children with nonsymptomatic generalized epilepsy in this age group, it is not possible to classify firmly the epilepsy and/or the seizures immediately after the intake. Instead, they are reclassified during the course of the disease. This and the apparent heterogeneity of the category IGE not otherwise specified point to inherent drawbacks of the current International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The prognosis of IGE at this young age is generally excellent.
Anxiety at age 15 predicts psychiatric diagnoses and suicidal ideation in late adolescence and young adulthood: results from two longitudinal studies
Publisher: Springer Science and Business Media LLC
Date: 14-11-2019
DOI: 10.1186/S12888-019-2349-3
Abstract: Anxiety disorders in adolescence have been associated with several psychiatric outcomes. We sought to describe the prospective relationship between various levels of adolescent anxiety and psychiatric diagnoses (anxiety-, bipolar sychotic-, depressive-, and alcohol and drug misuse disorders) and suicidal ideation in early adulthood while adjusting for childhood attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, we aimed to estimate the proportion attributable to the various anxiety levels for the outcomes. We used a nation-wide population-based Swedish twin study comprising 14,106 fifteen-year-old twins born in Sweden between 1994 and 2002 and a replication s le consisting of 9211 Dutch twins, born between 1985 and 1999. Adolescent anxiety was measured with parental and self-report. Psychiatric diagnoses and suicidal ideation were retrieved from the Swedish National Patient Register and via self-report. Adolescent anxiety, of various levels, predicted, in the Swedish National Patient Register, anxiety disorders: hazard ratio (HR) = 4.92 (CI 3.33–7.28) depressive disorders: HR = 4.79 (3.23–7.08), and any psychiatric outcome: HR = 3.40 (2.58–4.48), when adjusting for ADHD, ASD, and DCD. The results were replicated in the Dutch data. The proportion of psychiatric outcome attributable to adolescent anxiety over time (age 15–21) was 29% for any psychiatric outcome, 43–40% for anxiety disorders, and 39–38% for depressive disorders. Anxiety in adolescence constitutes an important risk factor in the development of psychiatric outcomes, revealing unique predictions for the different levels of anxiety, and beyond the risk conferred by childhood ADHD, ASD, and DCD. Developmental trajectories leading into psychiatric outcomes should further empirically investigated.
Genome‐wide association uncovers shared genetic effects among personality traits and mood states
Publisher: Wiley
Date: 24-05-2012
DOI: 10.1002/AJMG.B.32072
Life events, anxious depression and personality: A prospective and genetic study
Publisher: Cambridge University Press (CUP)
Date: 25-02-2008
DOI: 10.1017/S0033291708002985
Abstract: The association between life events and anxious depression might be due to causality or to gene–environment correlation. We examined unidirectional and reciprocal causality and a gene–environment correlation model, in which genes that influence the vulnerability for anxious depression also increase the risk of exposure to life events. The effect of genes that influence environmental exposure might be mediated through personality and we therefore also examined the association between life events and personality (neuroticism and extraversion). Information on life events, anxious depression, neuroticism and extraversion was collected in 5782 monozygotic (MZ) and dizygotic (DZ) twins who participated in a longitudinal survey study of the Netherlands Twin Register. To examine causality, data were analysed longitudinally. To examine gene–environment correlation, the co-twin control method was used. Anxious depression and, to a lesser extent, neuroticism scores increased after exposure to life events. Anxious depression and neuroticism also predicted the experience of life events. Prospectively, extraversion was not associated with life events. Anxious depression, neuroticism and extraversion scores did not differ between the non-exposed subjects of MZ and DZ twin pairs and unrelated subjects discordant for life events. Our findings suggest that reciprocal causation explains the relationship between life events and anxious depression and between life events and neuroticism. Extraversion is not related to life events. No evidence was found for gene–environment correlation, i.e. the genes that influence anxious depression, neuroticism or extraversion do not overlap with the genes that increase the risk of exposure to life events.
Heritability of Anxious-Depressive and Withdrawn Behavior
Publisher: Elsevier BV
Date: 03-2010
Genetic Variation at the TPH2 Gene Influences Impulsivity in Addition to Eating Disorders
Publisher: Springer Science and Business Media LLC
Date: 14-12-2012
DOI: 10.1007/S10519-012-9569-3
Abstract: Genes are involved in eating disorders (EDs) and self-induced vomiting (SV), a key symptom of different types of EDs. Perfectionism and impulsivity are potential risk factors for EDs. TPH2 (tryptophan hydroxylase 2) SNP rs1473473 was previously associated with anorexia nervosa and EDs characterized by SV. Could perfectionism or impulsivity be underlying the association between rs1473473 and EDs? Genetic association between TPH2 SNP rs1473473 and perfectionism or impulsivity was first evaluated in a random control group (N = 512). The associations obtained in this control group were subsequently tested in a group of patients with an ED (N = 267). The minor allele of rs1473473 (OR = 1.49) was more frequent in impulsive controls, but also in impulsive patients with an ED (OR = 1.83). The largest effect was found in the patients with an ED characterized by SV (OR = 2.51, p = 0.02). Genetic variation at the TPH2 gene appeared to affect impulsivity which, in turn, might predispose to the SV phenotype.
Anorexia nervosa and the Val158Met polymorphism of the COMT gene
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
Common variants at 6q22 and 17q21 are associated with intracranial volume
Publisher: Springer Science and Business Media LLC
Date: 15-04-2012
DOI: 10.1038/NG.2245
Maternal prenatal smoking and offspring emotional problems: No moderating effect of maternal or child 5-HTTLPR genotype
Publisher: Wiley
Date: 22-10-2012
DOI: 10.1002/AJMG.B.32110
A genome-wide association meta-analysis identifies new childhood obesity loci
Publisher: Springer Science and Business Media LLC
Date: 08-04-2012
DOI: 10.1038/NG.2247
Maternal environmental risk factors and the development of internalizing and externalizing problems in childhood: The complex role of genetic factors
Publisher: Wiley
Date: 24-08-2019
DOI: 10.1002/AJMG.B.32755
An association between Epac‐1 gene variants and anxiety and depression in two independent samples
Publisher: Wiley
Date: 21-12-2009
DOI: 10.1002/AJMG.B.30976
Short research article: COVID‐19 and its impact on child and youth mental health service demand in the community and emergency department
Publisher: Wiley
Date: 15-08-2022
DOI: 10.1111/CAMH.12593
Abstract: To explore changes in child and youth mental health service (CYMHS) demand in Brisbane, Australia, following the COVID pandemic. The number of monthly presentations and referrals to respectively the emergency department (ED) and community CYMHS were compared among 2018, 2019 and 2020. The study shows a marked increase in referrals to ED starting from July and in the community from May 2020. In the population referred to as community teams, the proportions of Indigenous children and those from lower socio‐economic areas decreased. The COVID‐19 pandemic has aggravated the supply and demand disparity in CYMHS, with the largest effect on the most vulnerable families.
Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder
Publisher: Cold Spring Harbor Laboratory
Date: 18-04-2018
DOI: 10.1101/304113
Abstract: The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics and genetically predicted expression levels in different tissues, using our online tool Drug Targetor (drugtargetor.com). We also investigated drug-target relationships and drug effects on gene expression that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 25 druggable genes were significantly associated with MDD after multiple testing correction, and 19 were suggestively significant. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new – and better – treatment options.
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
Publisher: Springer Science and Business Media LLC
Date: 23-07-2014
DOI: 10.1038/NATURE13545
Serotonin Transporter Gene
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
Validity of LIDAS (LIfetime Depression Assessment Self-report): a self-report online assessment of lifetime major depressive disorder
Publisher: Cambridge University Press (CUP)
Date: 05-10-2016
DOI: 10.1017/S0033291716002312
Abstract: There is a paucity of valid, brief instruments for the assessment of lifetime major depressive disorder (MDD) that can be used in, for ex le, large-scale genomics, imaging or biomarker studies on depression. We developed the LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD diagnosis according to DSM criteria, and is largely based on the widely used Composite International Diagnostic Interview (CIDI). Here, we tested the feasibility and determined the sensitivity and specificity for measuring lifetime MDD with this new questionnaire, with a regular CIDI as reference. Sensitivity and specificity analyses of the online lifetime MDD questionnaire were performed in adults with ( n = 177) and without ( n = 87) lifetime MDD according to regular index CIDIs, selected from the Netherlands Study of Depression and Anxiety (NESDA) and Netherlands Twin Register (NTR). Feasibility was tested in an additional non-selective, population-based s le of NTR participants ( n = 245). Of the 753 invited persons, 509 (68%) completed the LIDAS, of which 419 (82%) did this online. User-friendliness of the instrument was rated high. Median completion time was 6.2 min. Sensitivity and specificity for lifetime MDD were 85% [95% confidence interval (CI) 80–91%] and 80% (95% CI 72–89%), respectively. This LIDAS instrument gave a lifetime MDD prevalence of 20.8% in the population-based s le. Measuring lifetime MDD with an online instrument was feasible. Sensitivity and specificity were adequate. The instrument gave a prevalence of lifetime MDD in line with reported population prevalences. LIDAS is a promising tool for rapid determination of lifetime MDD status in large s les, such as needed for genomics studies.
Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression
Publisher: Springer Science and Business Media LLC
Date: 12-11-2013
Social and Economic Costs of Attention-Deficit/Hyperactivity Disorder Across the Lifespan
Publisher: SAGE Publications
Date: 13-10-2020
Abstract: To determine the financial and non-financial costs of Attention-Deficit/Hyperactivity Disorder (ADHD) across the lifespan. The population costs of ADHD in Australia were estimated for the financial year 2018 to 2019 using a prevalence approach to cost estimation across all ages. Financial (healthcare, productivity, education and justice systems, and deadweight losses) and non-financial costs were measured (Disability Adjusted Life Years (DALYs)). The total social and economic cost of ADHD in 2018 to 2019 were US$12.76 billion (range US$8.40 billion to US$17.44 billion, with per person costs of US$15,664 per year). Productivity costs made up 81% of the total financial costs, followed by deadweight losses (11%), and health system costs (4%). Loss in terms of wellbeing was significant (US$5.31 billion). There is a need to raise public awareness of the considerable socioeconomic impact and burden of ADHD in order to drive investment and policy decisions that improve identification and treatment of ADHD.
Influence of Candidate Genes on Attention Problems in Children: A Longitudinal Study
Publisher: Springer Science and Business Media LLC
Date: 30-10-2010
Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JAAC.2021.11.035
Abstract: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for s le overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. The meta-analysis of overall internalizing symptoms (INT Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood s les will be key in paving the way to future GWAS success.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects
Publisher: Springer Science and Business Media LLC
Date: 03-2019
Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years
Publisher: Cambridge University Press (CUP)
Date: 04-09-2014
DOI: 10.1017/S003329171400213X
Abstract: The influence of genetic factors on major depressive disorder is lower than on other psychiatric disorders. Heritability estimates mainly derive from cross-sectional studies, and knowledge on the longitudinal aetiology of symptoms of anxiety and depression (SxAnxDep) across the lifespan is limited. We aimed to assess phenotypic, genetic and environmental stability in SxAnxDep between ages 3 and 63 years. We used a cohort-sequential design combining data from 49 524 twins followed from birth to age ⩾20 years, and from adolescence into adulthood. SxAnxDep were assessed repeatedly with a maximum of eight assessments over a 25-year period. Data were ordered in 30 age groups and analysed with longitudinal genetic models. Over age, there was a significant increase during adolescence in mean scores with sex differences (women men) emerging. Heritability was high in childhood and decreased to 30–40% during adulthood. This decrease in heritability was due to an increase in environmental variance. Phenotypic stability was moderate in children (correlations across ages ~0.5) and high in adolescents ( r = 0.6), young adults ( r = 0.7), and adults ( r = 0.8). Longitudinal stability was mostly attributable to genetic factors. During childhood and adolescence there was also significant genetic innovation, which was absent in adults. Environmental effects contributed to short-term stability. The substantial stability in SxAnxDep is mainly due to genetic effects. The importance of environmental effects increases with age and explains the relatively low heritability of depression in adults. The environmental effects are transient, but the contribution to stability increases with age.
Genetic and environmental stability in attention problems across the lifespan: Evidence from the netherlands twin register
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.JAAC.2012.10.009
Abstract: To review findings on attention-deficit/hyperactivity disorder and attention problems (AP) in children, adolescents, and adults, as established in the database of the Netherlands Twin Register and increase the understanding of stability in AP across the lifespan as a function of genetic and environmental influences. A longitudinal model was fitted on Netherlands Twin Register AP scores from 44,607 child ( 18-year-old) twins. Mean AP showed a downward trend with age. Age-to-age correlations ranged from 0.33 (50-≥60 years old) to 0.73 (10-12 years old). Stability in in idual differences in AP was due to genetic and environmental factors, and change was due primarily to environmental factors. Nonadditive genetic influences were present from childhood to adulthood. Total genetic variance decreased slightly throughout aging, whereas environmental variance increased substantially with the switch from maternal to self-ratings at 12 years of age. As a result, heritability coefficients decreased from 0.70 to 0.74 in childhood (maternal ratings) to 0.51 to 0.56 in adolescence (self-ratings), and 0.40 to 0.54 in adulthood (self-ratings). In childhood, male subjects scored higher than female subjects. After the rater switch at 12 years of age, female subjects tended to score higher than male subjects. Stability of AP is the result of genetic and environmental stability. The decrease in estimated heritability at 12 years of age is due to an increase in occasion-specific environmental variance and likely reflects a methodologic effect. Because environmental influences have lasting effects on AP, their early detection is crucial.
Multivariate analyses of molecular genetic associations between childhood psychopathology and adult mood disorders and related traits
Publisher: Wiley
Date: 15-11-2022
DOI: 10.1002/AJMG.B.32922
Abstract: Ubiquitous associations have been detected between different types of childhood psychopathology and polygenic risk scores based on adult psychiatric disorders and related adult outcomes, indicating that genetic factors partly explain the association between childhood psychopathology and adult outcomes. However, these analyses in general do not take into account the correlations between the adult trait and disorder polygenic risk scores. This study aimed to further clarify the influence of genetic factors on associations between childhood psychopathology and adult outcomes by accounting for these correlations. Using a multivariate multivariable regression, we analyzed associations of childhood attention‐deficit/hyperactivity disorder (ADHD), internalizing, and social problems, with polygenic scores (PGS) of adult disorders and traits including major depression, bipolar disorder, subjective well‐being, neuroticism, insomnia, educational attainment, and body mass index (BMI), derived for 20,539 children aged 8.5–10.5 years. After correcting for correlations between the adult phenotypes, major depression PGS were associated with all three childhood traits, that is, ADHD, internalizing, and social problems. In addition, BMI PGS were associated with ADHD symptoms and social problems, while neuroticism PGS were only associated with internalizing problems and educational attainment PGS were only associated with ADHD symptoms. PGS of bipolar disorder, subjective well‐being, and insomnia were not associated with any childhood traits. Our findings suggest that associations between childhood psychopathology and adult traits like insomnia and subjective well‐being may be primarily driven by genetic factors that influence adult major depression. Additionally, specific childhood phenotypes are genetically associated with educational attainment, BMI and neuroticism.
Sex Differences in Genetic Architecture of Complex Phenotypes?
Publisher: Public Library of Science (PLoS)
Date: 18-12-2012
Effects of Chorionicity and Zygosity on Triplet Birth Weight
Publisher: Cambridge University Press (CUP)
Date: 28-03-2012
Abstract: Birth weight in triplets is, on average, lower than in singletons and twins, and more children are classified as having very low or extremely low birth weight. Still, there is limited research on factors that affect triplet birth weight, and s les under study are often small. Chorionicity and zygosity influence triplet birth weight, but it is unknown whether the effect of zygosity can be entirely ascribed to the effect of chorionicity or whether zygosity has an additional effect on triplet birth weight. This question was investigated in 346 triplets (from 116 trios) registered with the Netherlands Twin Register for whom data on chorionicity were available. ‘Triplet’ refers to one child and the set of three triplets is referred to as ‘trio’. Trios and triplets were classified based on zygosity and chorionicity. With regression analysis, the effects of zygosity and chorionicity on triplet birth weight were examined, while controlling for gestational age, sex, and maternal smoking during pregnancy. In addition, within the dizygotic trios a within-family comparison was made between the birth weight of the triplets that were part of a monozygotic pair (with some pairs sharing a chorion), and the birth weight of the dizygotic triplet. Based on the classification on in idual level, monozygotic, monochorionic triplets had a lower mean birth weight than dizygotic, dichorionic triplets. Most remarkably, in dizygotic trios, monozygotic pairs only had a lower mean birth weight than their dizygotic sibling triplet when the pair shared a chorion. We conclude that having shared a chorion, rather than being monozygotic, increases the risk of a low birth weight.
Child Care, Socio-economic Status and Problem Behavior: A Study of Gene-Environment Interaction in Young Dutch Twins
Publisher: Springer Science and Business Media LLC
Date: 31-05-2014
DOI: 10.1007/S10519-014-9660-Z
Abstract: The influences of formal child care before age 4 on behavioral problems at 3, 5, and 7 years of age were assessed in 18,932 Dutch twins (3,878 attended formal child care). The effect of formal child care was studied on the average level of problem behavior and as moderator of genetic and non-genetic influences, while taking into account effects of sex and parental socio-economic status (SES). There was a small association between attending formal child care and higher externalizing problems, especially when SES was low. Heritability was lower for formal child care and in lower SES conditions. These effects were largest at age 7 and for externalizing problems. In 7 year-old boys and girls, the difference in heritability between the formal child care group of low SES and the home care group of high SES was 30% for externalizing and ~20% for internalizing problems. The decrease in heritability was explained by a larger influence of the environment, rather than by a decrease in genetic variance. These results support a bioecological model in which heritability is lower in circumstances associated with more problem behavior.
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
Erratum: Crying without a cause and being easily upset in two-year-olds: Heritability and predictive power of behavioral problems (Twin Research and Human Genetics (2011) 14 (393-400) doi:10.1375/twin.14.5.393)
Publisher: Cambridge University Press (CUP)
Date: 08-2013
DOI: 10.1017/THG.2012.52
Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?
Publisher: Springer Science and Business Media LLC
Date: 18-03-2023
DOI: 10.1038/S41398-023-02348-Y
Abstract: Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain in idual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this s le, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining in idual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale s les of genotyped families with information on childhood psychiatric outcomes.
Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 20-06-2017
DOI: 10.1038/TP.2017.115
Abstract: Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient s les worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD ( P =4.42 × 10 −7 ) and PKP4 ( P =8.67 × 10 −7 ) and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P FDR =0.019 FDR, false discovery rate). Prior studies have implicated DPYD , PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP ( r g =0.28 [ P =2.99 × 10 −3 ]), SCZ ( r g =0.34 [ P =4.37 × 10 −5 ]) and MDD ( r g =0.57 [ P =1.04 × 10 −3 ]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JAD.2012.08.044
Abstract: There is ongoing interest in the possible interaction of the serotonin-transporter-linked polymorphic region (5-HTTLPR) with environmental factors in determining Major Depressive Disorder (MDD). The current study contributes to this research area by comprehensively examining the interaction-effects and direct-effects of 5-HTTLPR and five environmental factors on MDD prevalence and course in a well-characterized longitudinal s le. The s le consisted of 1625 patients with a CIDI-confirmed diagnosis of MDD and 1698 screened controls from the Netherlands. Four MDD outcomes were studied as dependent variables: one main MDD prevalence-outcome (all MDD), two more severe MDD prevalence-outcomes (suicidal and chronic MDD), and one MDD course outcome (chronic versus non-chronic MDD). Because SNP rs25531 modifies the effect of 5-HTTLPR, haplotypes of 5-HTTLPR and rs25531 were measured. For the four MDD outcome measures, we examined the direct effects of 5-HTTLPR/rs25531-haplotypes, five environmental factors (lifetime and recent stressful life-events, sexual abuse, low educational attainment, and childhood trauma) and their interaction in logistic regression models. The environmental factors had large and consistent effects on all four MDD outcomes, including course of MDD. The 5-HTTLPR/rs25531-haplotype had a suggestive effect on course of MDD, but not on presence of MDD. Gene-by-environment interaction was significant (<0.05) for one of the 20 tests performed, which is not more than expected by chance. Environmental factors were not assessed before the onset of MDD. Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.
Childhood and adolescent anxiety and depression: Beyond heritability
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.JAAC.2010.05.013
Abstract: To review the methodology of behavior genetics studies addressing research questions that go beyond simple heritability estimation and illustrate these using representative research on childhood and adolescent anxiety and depression. The classic twin design and its extensions may be used to examine age and gender differences in the genetic determinants of complex traits and disorders, the role of genetic factors in explaining comorbidity, the interaction of genes and the environment, and the effect of social interaction among family members. An overview of the methods typically employed to address such questions is illustrated by a review of 34 recent studies on childhood anxiety and depression. The review provides relatively consistent evidence for small to negligible sex differences in the genetic etiology of childhood anxiety and depression, a substantial role of genetic factors in accounting for the temporal stability of these disorders, a partly genetic basis of the comorbidity between anxiety and depression, a possible role of the interaction between genotype and the environment in affecting liability to these disorders, a role of genotype-environment correlation, and a minor, if any, etiological role of sibling interaction. The results clearly demonstrate a role for genetic factors in the etiology and temporal stability of in idual differences in childhood anxiety and depression. Clinical implications of the findings are discussed.
Evidence for Gender-Dependent Genotype by Environment Interaction in Adult Depression
Publisher: Springer Science and Business Media LLC
Date: 14-10-2016
Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients
Publisher: American Psychiatric Association Publishing
Date: 12-2010
Correction: Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank
Publisher: Springer Science and Business Media LLC
Date: 18-05-2020
A genome-wide association study of total child psychiatric problems scores
Publisher: Cold Spring Harbor Laboratory
Date: 05-06-2020
DOI: 10.1101/2020.06.04.20121061
Abstract: Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium. The SNP heritability of total psychiatric problems was 5.4% (SE=0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2 , a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total psychiatric problem score were shared with known genetic variants for common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (r G 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (r G 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation of with intelligence, educational attainment, wellbeing, smoking, and body fat (r G 0.29).The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between psychiatric disorders and related traits.
The Serotonin Transporter Gene Length Polymorphism (5-HTTLPR) and Life Events: No Evidence for an Interaction Effect on Neuroticism and Anxious Depressive Symptoms
Publisher: Cambridge University Press (CUP)
Date: 12-2010
Abstract: The finding of a significant gene by environment interaction effect on depression of the serotonin transporter length polymorphism (5-HTTLPR) and the Number of experienced Life Events (NLE) was not replicated in two large meta-analyses (Munafo et al., 2009 Risch et al., 2009). These meta-analyses have been criticized on the grounds that large studies that get most weight in meta-analyses have the poorest measurement quality of life events and, as a consequence, do not find an effect. Another issue is the time frame across which the NLE are measured. Proximal life events appear to be better predictors of depression than more distal events. We present the results of analyses of the 5-HTTLPR × NLE effect on anxious depression and neuroticism scores in a s le of 1,155 twins and their parents and siblings from 438 families. The interaction effect was tested separately for NLE experienced across the life span and NLE experienced in the past year. There was a significant main effect of NLE on anxious depression and neuroticism, especially when these were experienced in the past year. No interaction with 5-HTTLPR was found for NLE either experienced across the life span or across the past year. Our results support the two recent meta-analyses. Given recent insights from genome wide association studies, it seems more useful to focus on the joint effect of several genes, that are, for ex le, part of the same biological pathway, in interaction with the environment, than on one candidate gene.
A powerful phenotype for gene-finding studies derived from trajectory analyses of symptoms of anxiety and depression between age seven and 18
Publisher: Wiley
Date: 03-09-2016
DOI: 10.1002/AJMG.B.32375
Genome-Wide Linkage Analysis of Multiple Measures of Neuroticism of 2 Large Cohorts From Australia and the Netherlands
Publisher: American Medical Association (AMA)
Date: 02-06-2008
Using electronic health record data to predict future self‐harm or suicidal ideation in young people treated by child and youth mental health services
Publisher: Wiley
Date: 14-08-2023
DOI: 10.1111/SLTB.12988
Abstract: Identifying young people who are at risk of self‐harm or suicidal ideation (SHoSI) is a priority for mental health clinicians. We explore the utility of routinely collected data in developing a tool to aid early identification of those at risk. We used electronic health records of 4610 young people aged 5–19 years who were treated by Child and Youth Mental Health Services (CYMHS) in greater Brisbane, Australia. Two Lasso models were trained to predict the risk of future SHoSI in young people currently rated SHoSI and those who were not. For currently non‐SHoSI children, an Area Under the Receiver Operating Characteristics (AUC) of 0.78 was achieved. Those with the highest risk were 4.97 (CI 4.35–5.66) times more likely to be categorized as SHoSI in the future. For current SHoSI children, the AUC was 0.62. A prediction model with fair overall predictive power for currently non‐SHoSI children was generated. Predicting persistence for SHoSI was more difficult. The electronic health records alone were not sufficient to discriminate at acceptable levels and may require adding unstructured data such as clinical notes. To optimally predict SHoSI models need to be tested and validated separately for those young people with varying degrees of risk.
Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals
Publisher: American Medical Association (AMA)
Date: 07-2020
Do Parental Psychiatric Symptoms Predict Outcome in Children With Psychiatric Disorders? A Naturalistic Clinical Study
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JAAC.2018.05.017
Abstract: Parental psychiatric symptoms can negatively affect the outcome of children's psychopathology. Studies thus far have mainly shown a negative effect of maternal depression. This study examined the associations between a broad range of psychiatric symptoms in mothers and fathers and the child's outcome. Internalizing and externalizing psychiatric symptoms were assessed in 742 mothers, 440 fathers, and their 811 children at the first evaluation in 3 child and adolescent psychiatric outpatient clinics and at follow-up (on average 1.7 years later). Predictions of child's symptoms scores were tested at follow-up by parental symptom scores at baseline, parental scores at follow-up, and offspring scores at baseline. Children whose mother or father scored above the (sub)clinical threshold for psychiatric symptoms at baseline had higher symptom scores at baseline and at follow-up. Offspring follow-up scores were most strongly predicted by offspring baseline scores, in addition to parental psychiatric symptoms at follow-up. Offspring symptom scores at follow-up generally were not predicted by parental scores at baseline. Maternal and paternal associations were of similar magnitude. Higher symptom scores at follow-up in children of parents with psychopathology were mainly explained by higher symptom scores at baseline. Continuing parent-offspring associations could be a result of reciprocal effects, ie, parental symptoms influencing offspring symptoms and offspring symptoms influencing parental symptoms. Nevertheless, the results show that these children are at risk for persisting symptoms, possibly indicating the need to treat maternal and paternal psychopathology.
Systematic Review: Anxiety in Children and Adolescents With Chronic Medical Conditions
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.JAAC.2019.10.010
Abstract: Youth with chronic medical conditions (CMCs) have been reported to be at increased risk for developing anxiety disorders. Importantly, suffering from anxiety may also have an impact on their disease-related outcomes. This study set out to systematically review the literature on anxiety and seven CMCs (asthma, congenital heart disease, diabetes, epilepsy, inflammatory bowel disease, juvenile idiopathic arthritis, and sickle cell disease) among youth. A systematic review was performed according to the PRISMA statement. Searches were conducted across PubMed, PsycNET, Embase, and reference lists of the included studies (1990-2018). Three independent reviewers screened titles and abstracts and conducted full-text assessment. Studies were included if they reported the prevalence of anxiety or the association of anxiety on disease-related outcomes in children and/or adolescents with the focal CMCs. A total of 53 studies met the predetermined inclusion criteria. Across the CMCs, the prevalence of anxiety disorder was increased in youths with CMCs compared to the general population. Evidence for a relationship between anxiety and adverse disease-related outcomes was limited. For asthma, inflammatory bowel disease, and sickle cell disease, there was some evidence indicating that anxiety was associated with adverse outcomes supported by two longitudinal studies, one in asthma and one in inflammatory bowel disease. For diabetes, results were inconsistent with some studies indicating that anxiety was associated with worse and others with better treatment adherence. The prevalence of anxiety disorders in youth with CMCs is higher than that in the general population. Anxiety may also be associated with adverse disease-related outcomes for youths, but it is not possible to draw definitive conclusions. Longitudinal studies making use of parent/youth composite anxiety measures and a combination of parent/youth reported and objective measures of disease-related outcomes are needed. Given the burden of disease of anxiety disorders, regardless of the impact on the disease outcomes, screening for and treatment of anxiety is recommended in youths with CMCs.
The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies
Publisher: Cambridge University Press (CUP)
Date: 05-2005
DOI: 10.1017/S003329170400412X
Abstract: Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies. Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso. Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other. Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.
A genome-wide association meta-analysis of preschool internalizing problems
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.JAAC.2013.12.028
Abstract: Preschool internalizing problems (INT) are highly heritable and moderately genetically stable from childhood into adulthood. Gene-finding studies are scarce. In this study, the influence of genome-wide measured single nucleotide polymorphisms (SNPs) was investigated in 3 cohorts (total N = 4,596 children) in which INT was assessed with the same instrument, the Child Behavior Checklist (CBCL). First, genome-wide association (GWA) results were used for density estimation and genome-wide complex trait analysis (GCTA) to calculate the variance explained by all SNPs. Next, a fixed-effect inverse variance meta-analysis of the 3 GWA analyses was carried out. Finally, the overlap in results with prior GWA studies of childhood and adulthood psychiatric disorders and treatment responses was tested by examining whether SNPs associated with these traits jointly showed a significant signal for INT. Genome-wide SNPs explained 13% to 43% of the total variance. This indicates that the genetic architecture of INT mirrors the polygenic model underlying adult psychiatric traits. The meta-analysis did not yield a genome-wide significant signal but was suggestive for the PCSK2 gene located on chromosome 20p12.1. SNPs associated with other psychiatric disorders appeared to be enriched for signals with INT (λ = 1.26, p < .03). Our study provides evidence that INT is influenced by many common genetic variants, each with a very small effect, and that, even as early as age 3, genetic variants influencing INT overlap with variants that play a role in childhood and adulthood psychiatric disorders.
Birth weight in a large series of triplets
Publisher: Springer Science and Business Media LLC
Date: 04-2011
Author Index
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2008
Illicit drug use by mothers and their daughters in Australia: A comparison of two generations
Publisher: Elsevier BV
Date: 07-2020
The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data
Publisher: Springer Science and Business Media LLC
Date: 18-10-2011
DOI: 10.1038/TP.2011.45
Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
Publisher: Springer Science and Business Media LLC
Date: 16-03-2200
DOI: 10.1038/S41380-020-0689-5
Abstract: Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi
Identification of common genetic risk variants for autism spectrum disorder
Publisher: Springer Science and Business Media LLC
Date: 25-02-2019
Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting
Publisher: Wiley
Date: 22-11-2010
A twin-family study of the association between employment, burnout and anxious depression
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.JAD.2005.11.004
Abstract: Earlier studies have shown that employment and burnout are related to anxiety and depression. This twin-family study investigates to what extent these associations are caused by shared etiological factors. In a s le of 4,309 Dutch twins and 1,008 siblings, bivariate genetic analyses of employment and anxious depression and of burnout and anxious depression were carried out using structural equation modelling. Employment and anxious depression were both influenced by genetic and in idual-specific environmental factors. The association between employment and anxious depression was small, but significant, estimated at -0.08. Power was too low to decide whether the covariance was explained by genetic or environmental factors. In burnout, familial clustering was due to genetic factors in men, but to genetic and common environmental factors in women. In both sexes, there was a strong correlation of around 0.40 with anxious depression, which was explained by shared genetic and shared in idual-specific environmental factors. The group of unemployed subjects in our s le not only contained subjects who were searching for a job, but also subjects who were out of the labour force. Associations between employment and anxious depression as well as between burnout and anxious depression are due to overlapping genetic and in idual-specific environmental factors. Work related circumstances, e.g. financial strain or work-family conflict, might be of importance in burnout and anxious depression. These results support the notion that a genetic vulnerability for depression also increases the risk for exposure to high-risk environments, such as unemployment.
The Young Netherlands Twin Register (YNTR): Longitudinal Twin and Family Studies in Over 70,000 Children
Publisher: Cambridge University Press (CUP)
Date: 28-11-2012
DOI: 10.1017/THG.2012.118
Abstract: The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological s les have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.
Analysis of Behavioral and Emotional Problems in Children Highlights the Role of Genotype × Environment Interaction
Publisher: Wiley
Date: 28-10-2015
DOI: 10.1111/CDEV.12451
Abstract: This study tested for Genotype × Environment (G × E) interaction on behavioral and emotional problems in children using new methods that do not require identification of candidate genes or environments, can distinguish between interaction with shared and unique environment, and are insensitive to scale effects. Parental ratings of problem behavior from 14,755 twin pairs (5.3 years, SD = 0.22) indicated G × E interaction on emotional liability, social isolation, aggression, attention problems, dependency, anxiety, and physical coordination. Environmental influences increased in children who were genetically more predisposed to problem behavior, with ~20% of the variance due to G × E interaction (8% for anxiety to 37% for attention problems). Ignoring G × E interaction does not greatly bias heritability estimates, but it does offer a comprehensive model of the etiology for childhood problems.
A genetically informed prediction model for suicidal and aggressive behaviour in teens.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2022
DOI: 10.1038/S41398-022-02245-W
Abstract: Suicidal and aggressive behaviours cause significant personal and societal burden. As risk factors associated with these behaviours frequently overlap, combined approaches in predicting the behaviours may be useful in identifying those at risk for either. The current study aimed to create a model that predicted if in iduals will exhibit suicidal behaviour, aggressive behaviour, both, or neither in late adolescence. A s le of 5,974 twins from the Child and Adolescent Twin Study in Sweden (CATSS) was broken down into a training (80%), tune (10%) and test (10%) set. The Netherlands Twin Register (NTR N = 2702) was used for external validation. Our longitudinal data featured genetic, environmental, and psychosocial predictors derived from parental and self-report data. A stacked ensemble model was created which contained a gradient boosted machine, random forest, elastic net, and neural network. Model performance was transferable between CATSS and NTR (macro area under the receiver operating characteristic curve (AUC) [95% CI] AUC
Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/BMJOPEN-2020-046830
Abstract: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).
The nature and management of metastatic melanoma after progression on braf inhibitors: Effects of extended BRAF inhibition
Publisher: Wiley
Date: 07-2014
DOI: 10.1002/CNCR.28851
Abstract: The v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor (BRAFi) drugs dabrafenib and vemurafenib have high response rates in BRAF-mutant, metastatic melanoma however, 50% of patients progress by 7 months. In this study, the authors examined the nature and management of disease progression (PD) on BRAFi treatment, including characteristics and outcomes of patients who received continued BRAFi treatment beyond disease progression (TBP). Clinicopathologic data at baseline and at the time of PD were collected for all patients with BRAF-mutant metastatic melanoma who received BRAFi monotherapy within clinical trials between July 2009 and September 2012. Management and survival after PD were examined, including continued BRAFi TBP (> 28 days beyond Response Evaluation Criteria in Solid Tumor [RECIST]-defined PD). Ninety-five of 114 BRAFi-treated patients had PD. Fifty-three of those 95 patients (56%) progressed in extracranial sites alone, 18% (17 of 95 patients) progressed in intracranial and extracranial sites simultaneously, and 16% (15 of 95 patients) progressed in intracranial sites alone. Twenty-nine of the 95 patients (31%) who had PD progressed in a single site or organ, 48% (46 of 95 patients) progressed in existing metastases only, and 18% (17 of 95 patients) had new metastases alone. At the time of PD, 35 of 95 patients (37%) received no subsequent systemic treatment, 20% (19 of 95 patients) changed systemic treatments, and 39% (37 of 95 patients) continued BRAFi TBP for a median of 97 days. BRAFi TBP and known prognostic factors (Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, RECIST sum of the greatest dimensions of target lesions) were associated with overall survival (OS) from the time of PD however, in multivariable analysis, BRAFi TBP improved OS (hazard ratio, 0.50 95% confidence interval, 0.27-0.93 P = .029). Most BRAFi-treated patients progressed in existing extracranial sites, and 31% progressed in isolated sites. Compared with cessation, continued BRAFi TBP is associated with prolonged OS even after adjusting for potential prognostic factors at PD.
Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype
Publisher: Springer Science and Business Media LLC
Date: 14-08-2007
Characteristics and treatment outcomes of children and adolescents accessing treatment in Child and Youth Mental Health Services
Publisher: Wiley
Date: 03-02-2022
DOI: 10.1111/EIP.13275
Abstract: To provide insight into the characteristics and treatment outcomes of children and adolescents accessing outpatient Child and Youth Mental Health Services (CYMHS), and to explore whether outcomes differ by age, sex, and ancestry background. This information can guide how to optimize the treatment delivered at these services. An observational retrospective study was performed based on data from 3098 children and adolescents between age 5 and 18 who received treatment at Brisbane, Australia, community CYMHS between 2013–2018. Patient characteristics, service use, and clinician and parent rated Routine Outcome Measures (ROM) were extracted from electronic health records. Anxiety and mood disorders were the most common mental disorders (37% and 19%). In 1315 children and adolescents (42%), two or more disorders were diagnosed, and the far majority (88%) had experienced at least one psychosocial stressor. The ROM scores improved between start and end of treatment with Cohen's d effect sizes of around 0.9. However, ~50% of the children still scored in the clinical range at the end of treatment. Outcomes did not differ over gender and Indigenous status. Children and adolescents accessing CYMHS have severe and complex mental disorders as reflected by high rates of comorbidity, exposure to adverse circumstances and high symptom scores at the start of treatment. Despite the clinically relevant and substantial improvement, end ROM scores indicated the presence of residual symptoms. As this increases the risk for relapse, services should explore ways to improve treatment to further reduce mental health symptoms.
Familial clustering in burnout: a twin-family study
Publisher: Cambridge University Press (CUP)
Date: 2005
DOI: 10.1017/S0033291704002983
Abstract: Research on risk factors for burnout has mainly focused on circumstances at work and on personal characteristics. The aim of this study was to investigate whether burnout clusters within families and, if so, whether this is due to genetic influences or to environmental factors shared by family members. Finally, we tried to identify specific risk factors for burnout. In 2707 twins, 736 of their siblings and 575 of their spouses from a population-based twin-family s le, burnout was measured using a self-report questionnaire. Correlations in burnout scores were obtained for monozygotic and dizygotic twin pairs and sibling pairs conditional on the pairs' sex. Correlations for twins and their spouses were derived conditional on the length of the relationship. In the final model, correlations of the monozygotic and dizygotic twin pairs and sibling pairs were significantly different from zero, but not significantly different from each other. The correlation was estimated at 0.22. The correlation between spouses was also significant. This was mainly due to the group with a relationship longer than 5 years in which the correlation was 0.24. Burnout scores were higher in subjects whose parents had a high level of education. There is familial clustering for burnout due to environmental factors shared by family members, explaining 22 % of the variance. Genetic factors do not seem to be of importance. The significant correlation between spouses supports the conclusion that common environment plays a role in burnout. A high parental education is one of the familial risk factors.
Assessment and characterization of phenotypic heterogeneity of anxiety disorders across five large cohorts
Publisher: Wiley
Date: 15-07-2016
DOI: 10.1002/MPR.1519
The association between trauma exposure, polygenic risk and individual depression symptoms
Publisher: Elsevier BV
Date: 03-2023
Heritability of Behavioral Problems in 7-Year Olds Based on Shared and Unique Aspects of Parental Views
Publisher: Springer Science and Business Media LLC
Date: 28-10-2017
Maternal and paternal effects on offspring internalizing problems: Results from genetic and family‐based analyses
Publisher: Wiley
Date: 05-2020
DOI: 10.1002/AJMG.B.32784
Symptom-level modelling unravels the shared genetic architecture of anxiety and depression
Publisher: Springer Science and Business Media LLC
Date: 15-04-2021
Nick Martin and the Genetics of Depression: Sample Size, Sample Size, Sample Size
Publisher: Cambridge University Press (CUP)
Date: 04-2020
DOI: 10.1017/THG.2020.13
Abstract: Nick Martin is a pioneer in recognizing the need for large s le size to study the complex, heterogeneous and polygenic disorders of common mental disorders. In the predigital era, questionnaires were mailed to thousands of twin pairs around Australia. Always quick to adopt new technology, Nick’s studies progressed to phone interviews and then online. Moreover, Nick was early to recognize the value of collecting DNA s les. As genotyping technologies improved over the years, these twin and family cohorts were used for linkage, candidate gene and genome-wide association studies. These cohorts have underpinned many analyses to disentangle the complex web of genetic and lifestyle factors associated with mental health. With characteristic foresight, Nick is chief investigator of our Australian Genetics of Depression Study, which has recruited 16,000 people with self-reported depression (plus DNA s les) over a time frame of a few months — analyses are currently ongoing. The mantra of s le size, s le size, s le size has guided Nick’s research over the last 30 years and continues to do so.
Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
DOI: 10.1038/S41380-019-0558-2
Abstract: Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 in iduals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
Further confirmation of the association between anxiety and CTNND2 : replication in humans
Publisher: Wiley
Date: 21-11-2013
DOI: 10.1111/GBB.12095
Abstract: The rat genome sequencing and mapping consortium found evidence for an association between the catenin-δ2 gene (CTNND2) and anxious behaviour. We replicated these results in humans by carrying out a genetic association test in patients with panic disorder, social phobia, generalized anxiety disorder and/or agoraphobia (N = 1714) and controls (N = 4125). We further explored the association between CTNND2 and other psychiatric disorders based on publicly available genome-wide association results. A gene-based test showed that single nucleotide polymorphisms (SNPs) in CTNND2 have a significantly increased signal (P < 1e(-5) ) and decreased P-values. Single nucleotide polymorphism rs1012176 showed the strongest association with any anxiety disorder (odds ratio: 0.8128, SE = 0.063, P = 0.00099), but this effect was not significant after correction for multiple testing. In available genome-wide association results from the Psychiatric Genomics Consortium we found that SNPs in CTNND2 collectively showed an increased signal for schizophrenia (P < 1e(-5) ) and major depressive disorder (P < 1e(-5) ), but not for bipolar disorder. These signals remained significant after correction for potential confounders. The association between CTNND2 and anxiety was not strong enough to be picked up in the current generation of human genome-wide analyses, indicating the usefulness of and need for animal genetic studies to identify candidate genes for further study in human s les.
Parents of children with psychopathology: psychiatric problems and the association with their child's problems
Publisher: Springer Science and Business Media LLC
Date: 13-01-2016
Genetic effects influencing risk for major depressive disorder in China and Europe
Publisher: Springer Science and Business Media LLC
Date: 28-03-2017
DOI: 10.1038/TP.2016.292
Abstract: Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33 female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497 log 10 Bayes Factor=8.08) but failed to replicate in an independent European s le ( P =0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
The Amsterdam Sexual Abuse Case (ASAC)-study in day care centers: Longitudinal effects of sexual abuse on infants and very young children and their parents, and the consequences of the persistence of abusive images on the internet
Publisher: Springer Science and Business Media LLC
Date: 08-11-2014
Editorial: Childhood Stress and Psychopathology: It's Not Too Early to Look at Biological Aging
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JAAC.2019.09.020
Abstract: There has been growing interest in the associations among biological aging, stress, and psychopathology. Biological aging reflects an in idual's functional and biological condition, and one of the indicators is telomere length.
A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Publisher: Springer Science and Business Media LLC
Date: 08-05-2020
DOI: 10.1038/S41467-020-16022-0
Abstract: Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery ( N = 10,674) and replication ( N = 11,214) imaging s le from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure ( β : 0.125 to 0.868, p FDR 0.043). Several behavioural traits are also associated with depression-PRS ( β : 0.014 to 0.180, p FDR : 0.049 to 1.28 × 10 −14 ) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Publisher: Elsevier BV
Date: 12-2019
Estimating Non-Response Bias in Family Studies: Application to Mental Health and Lifestyle
Publisher: Springer Science and Business Media LLC
Date: 07-2003
DOI: 10.1023/B:EJEP.0000036814.56108.66
Abstract: Non-response to mailed surveys reduces the effective s le size and may introduce bias. Non-response has been studied by (1) comparison to available data in population based registers, (2) directly contacting non-respondents by telephone or single-item reply cards, and (3) longitudinal repetition of the survey. The goal of this paper was to propose an additional method to study non-response bias: when the variable of interest has a familial component, data from respondents can be used as proxy for the data from their non-responding family members. This approach was used with data on smoking, alcohol consumption, physical activity, coffee- and tea-use, education, body mass index, religion, burnout, life events, personality and mental health in large number of siblings and DZ twins registered with the Netherlands Twin Register. In addition, for smoking behavior, we also used the second strategy by sending a reply card. Results show that scores of members from less cooperative families or incomplete twin pairs tended to be more unfavorable than the scores from highly cooperative families or complete twin pairs. For ex le, family members from less cooperative families cycled less often and scored higher on anxious depression and neuroticism. For smoking, both the results of the reply card and the results of the additional method suggested a higher percentage smokers among the non-respondents but this was only significant with reply card method. In general, differences between highly/less cooperative families and complete/incomplete DZ twins were small. Results suggest that, even for studies with moderate response rates, data collected on health, personality and lifestyle are relatively unbiased.
The impact of COVID ‐19 on children and adolescents attending Child and Youth Mental Health Services in Queensland, Australia
Publisher: Wiley
Date: 12-04-2023
DOI: 10.1111/EIP.13421
Abstract: This explorative study aims to provide insight into impacts of the COVID‐19 pandemic and associated restrictions, on mental health of children and adolescents treated at Child and Youth Mental Health Services, and their parents. The COVID‐19 Mental Health Survey was disseminated to parents of children and adolescents under treatment at community Child and Youth Mental Health Services (Brisbane, Australia) between July–November 2020 throughout different stages of COVID‐19 related restrictions. Parents of 110 children participated. Most reported child's symptoms were sadness (46%), anxiety (60%), lack of focus (61%), lack of joy in their usual activities (38%) and reduction in sleep (42%). Parental emotions were significantly correlated with their child's emotions. Parent's lack of enjoyment of usual activities had the overall strongest average correlation (0.27) but this was no longer significant once other variables were controlled for. Children who attended school remotely for some of the days had a significantly ( p .05) higher risk of having more reported symptoms. Interestingly, in later stages of the lockdown with further easing of restrictions, symptoms also tended to be more severe. Cross‐sectional data on children and adolescents in Queensland, Australia with pre‐existing mental health issues suggests mental health continued to deteriorate through the pandemic even as restrictions eased. Changes in schooling seem to be an especially important risk factor.
Editors’ Note and Special Communication: Research Priorities in Child and Adolescent Mental Health Emerging From the COVID-19 Pandemic
Publisher: Elsevier BV
Date: 05-2021
Spousal resemblance for smoking: Underlying mechanisms and effects of cohort and age
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.DRUGALCDEP.2015.05.018
Abstract: In this study we ask why spouses resemble each other in smoking behaviour and assess if such resemblance depends on period of data collection or age. Spousal similarity may reflect different, not mutually exclusive, processes. These include phenotypic assortment (choice of spouse is based on phenotype) or social homogamy at the time spouses first meet, and marital interaction during the relationship. Ever and current smoking were assessed between 1991 and 2013 in surveys of the Netherlands Twin Register for 14,230 twins and 1,949 of their spouses (mean age 31.4 [SD=14.0]), and 11,536 parents of twins (53.4 [SD=8.6]). Phenotypic assortment and social homogamy were examined cross-sectionally by calculating the probability of agreement between twins and their spouses, twins and their co-twin's spouse and spouses of both twins as a function of zygosity. Marital interaction was tested by investigating the association between relationship duration and spousal resemblance. Between 1991 and 2013 smoking declined in all age groups for both genders. Spousal resemblance for ever and current smoking was higher when data were more recent. For ever smoking, a higher age of men was associated with lower spousal resemblance. Phenotypic assortment was supported for both smoking measures, but social homogamy could not be excluded. No effect of marital interaction was found. Differences in smoking prevalence across time and age influence spousal similarity. In iduals more often choose a spouse with similar smoking behaviour (phenotypic assortment) causing higher genotypic similarity between them. Given the heritability of smoking this increases genetic risk of smoking in offspring.
Genetic risk profiles for depression and anxiety in adult and elderly cohorts
Publisher: Springer Science and Business Media LLC
Date: 22-06-2010
DOI: 10.1038/MP.2010.65
Effects of the ‘Circle of Security’ group parenting program (COS-P) with foster carers: An observational study
Publisher: Elsevier BV
Date: 08-2020
Discovery of biochemical biomarkers for aggression: A role for metabolomics in psychiatry
Publisher: Wiley
Date: 23-02-2016
DOI: 10.1002/AJMG.B.32435
Abstract: Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorders. We introduce the different classification systems of aggression and related disorders as a basis for discussing biochemical biomarkers and then present an overview of studies in humans (published between 1990 and 2015) that reported statistically significant associations of biochemical biomarkers with aggression, DSM-IV disorders involving aggression, and their subtypes. The markers are of different types, including inflammation markers, neurotransmitters, lipoproteins, and hormones from various classes. Most studies focused on only a limited portfolio of biomarkers, frequently a specific class only. When integrating the data, it is clear that compounds from several biological pathways have been found to be associated with aggressive behavior, indicating complexity and the need for a broad approach. In the second part of the paper, using ex les from the aggression literature and psychiatric metabolomics studies, we argue that a better understanding of aggression would benefit from a more holistic approach such as provided by metabolomics. © 2016 Wiley Periodicals, Inc.
Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes
Publisher: Springer Science and Business Media LLC
Date: 10-11-2017
DOI: 10.1038/S41598-017-11852-3
Abstract: Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-in idual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
Evidence for a causal association of low birth weight and attention problems
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.JAAC.2011.09.007
Abstract: Low birth weight (LBW) is associated with attention problems (AP) and attention-deficit/hyperactivity disorder (ADHD). The etiology of this association is unclear. We investigate whether there is a causal influence of birth weight (BW) on AP and whether the BW effect is mediated by catch-up growth (CUG) in low-BW children. Longitudinal data from >29,000 twins registered with the Netherlands Twin Register with BW ≥1,500 g and gestational age (GA) ≥32 weeks were analyzed with the cotwin control method. Hyperactivity and AP were assessed at ages 3, 7, 10, and 12 years weight was assessed at birth and age 2 years. Children in the lowest BW category of 1,500 to 2,000 g scored 0.18 to 0.37 standard deviations (SD) higher on AP than children in the reference category of 3,000 to 3,500 g. This effect was present in term-born and preterm-born children. Importantly, in BW discordant monozygotic (MZ), dizygotic (DZ), and unrelated (UR) pairs, the child with the lower BW scored higher on hyperactivity and AP than the child with the higher BW and within-pair differences were similar for MZ, DZ, and UR pairs. This pattern is consistent with a causal effect of BW on AP. MZ and DZ twin pairs concordant for LBW but discordant for CUG showed similar AP scores, thus ruling out any effect of CUG on AP. These results strongly indicate that the association of birth weight and AP represents a causal relationship. The effects of BW are not explained by CUG in LBW children.
Agency notification and retrospective self-reports of childhood maltreatment in a 30-Year cohort: Estimating population prevalence from different data sources
Publisher: Elsevier BV
Date: 11-2020
Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JAAC.2021.03.020
Abstract: A systematic review of studies using molecular genetics and statistical approaches to investigate the role of common genetic variation in the development, persistence, and comorbidity of childhood psychiatric traits was conducted. A literature review was performed using the PubMed database, following PRISMA guidelines. There were 131 studies meeting inclusion criteria, having investigated at least one type of childhood-onset or childhood-measured psychiatric disorder or trait with the aim of identifying trait-associated common genetic variants, estimating the contribution of single nucleotide polymorphisms (SNPs) to the amount of variance explained (SNP-based heritability), investigating genetic overlap between psychiatric traits, or investigating whether the stability in traits or the association with adult traits is explained by genetic factors. The first robustly associated genetic variants have started to be identified for childhood psychiatric traits. There were substantial contributions of common genetic variants to many traits, with variation in single nucleotide polymorphism heritability estimates depending on age and raters. Moreover, genetic variants also appeared to explain comorbidity as well as stability across a range of psychiatric traits in childhood and across the life span. Common genetic variation plays a substantial role in childhood psychiatric traits. Increased s le sizes will lead to increased power to identify genetic variants and to understand genetic architecture, which will ultimately be beneficial to targeted and prevention strategies. This can be achieved by harmonizing phenotype measurements, as is already proposed by large international consortia and by including the collection of genetic material in every study.
Borderline personality traits and adult attention‐deficit hyperactivity disorder symptoms: A genetic analysis of comorbidity
Publisher: Wiley
Date: 02-08-2011
DOI: 10.1002/AJMG.B.31226
Overview of CAPICE—Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe—an EU Marie Skłodowska-Curie International Training
Publisher: Springer Science and Business Media LLC
Date: 20-01-2021
DOI: 10.1007/S00787-020-01713-2
Abstract: The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of in idual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression
Publisher: Springer Science and Business Media LLC
Date: 26-04-2018
Suggestive linkage on chromosome 2, 8, and 17 for lifetime major depression
Publisher: Wiley
Date: 05-04-2009
DOI: 10.1002/AJMG.B.30817
Anxiety and depression in children and adults: influence of serotonergic and neurotrophic genes?
Publisher: Wiley
Date: 12-07-2010
Corrigendum to “Spousal resemblance for smoking: Underlying mechanisms and effects of cohort and age” [Drug Alcohol Depend. 153 (2015) 221–228] (S0376871615002549) (10.1016/j.drugalcdep.2015.05.018))
Publisher: Elsevier BV
Date: 2018
Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood
Publisher: Springer Science and Business Media LLC
Date: 21-06-2018
Examining the Educational Gap for Children with ADHD and Subthreshold ADHD
Publisher: SAGE Publications
Date: 14-12-2022
Abstract: The present study examined the impact of Attention Deficit Hyperactivity Disorder (ADHD) on core educational outcomes in two large community cohorts of Australian school children. Academic (reading and numeracy) and non-academic (school engagement, attendance, peer victimization, and parental expectations) outcomes were compared between children with ADHD, subthreshold ADHD, and controls when children were in grade 5 (M age = 10.5). Data were drawn from the Longitudinal Study of Australian Children birth cohort (LSAC Both subthreshold ADHD and ADHD groups had poorer outcomes on all measures, with medium effects sizes. Differences were not evident between subthreshold ADHD and ADHD groups. Educational outcomes examined in this study highlight the educational risk for upperprimary school children with ADHD or subthreshold ADHD, in comparison to their peers. Monitoring these outcomes is necessary to inform policy, practice, and intervention.
Detection of gene-environment interaction in pedigree data using genome-wide genotypes
Publisher: Springer Science and Business Media LLC
Date: 20-07-2016
DOI: 10.1038/EJHG.2016.88
Spousal resemblance in psychopathology: A comparison of parents of children with and without psychopathology
Publisher: Cambridge University Press (CUP)
Date: 2016
DOI: 10.1016/J.EURPSY.2016.01.2423
Abstract: Spouses resemble each other for psychopathology, but data regarding spousal resemblance in externalizing psychopathology, and data regarding spousal resemblance across different syndromes (e.g. anxiety in wives and attention deficit/hyperactivity disorder [ADHD] in husbands) are limited. Moreover, knowledge is lacking regarding spousal resemblance in parents of children with psychiatric disorders. We investigated and compared spousal resemblance within and across internalizing and externalizing symptom domains in parents of children with and without psychopathology. Symptoms of depression, anxiety, avoidant personality, ADHD, and antisocial personality were assessed with the Adult Self Report in 728 mothers and 544 fathers of 778 children seen in child and adolescent psychiatric outpatient clinics and in 2075 mothers and 1623 fathers of 2784 children from a population-based s le. Differences in symptom scores and spousal correlations between the s les were tested. Parents in the clinical s le had higher symptom scores than in the population-based s le. In both s les, correlations within and across internalizing and externalizing domains of psychopathology were significant. Importantly, correlations were significantly higher in the clinical s le ( P = 0.03). Correlations, within and across symptoms, ranged from 0.14 to 0.30 in the clinical s le and from 0.05 to 0.23 in the population-based s le. This large study shows that spousal resemblance is not only present within but also across symptom domains. Especially in the clinical s le, ADHD symptoms in fathers and antisocial personality symptoms in mothers were correlated with a range of psychiatric symptoms in their spouses. Clinicians need to be alert of these multiple affected families.
Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms: Application to Childhood Height
Publisher: Springer Science and Business Media LLC
Date: 03-06-2015
Ultra-rare and common genetic variant analysis converge to implicate negative selection and neuronal processes in the aetiology of schizophrenia
Publisher: Cold Spring Harbor Laboratory
Date: 29-05-2021
DOI: 10.1101/2021.05.26.21257794
Abstract: Both common and rare genetic variants (minor allele frequency 1% and 0.1% respectively) have been implicated in the aetiology of schizophrenia. In this study, we integrate single-cell gene expression data with publicly available Genome-Wide Association Study (GWAS) and exome sequenced data in order to investigate in parallel, the enrichment of common and (ultra-)rare variants related to schizophrenia in several functionally relevant gene-sets. Four types of gene-sets were constructed 1) protein-truncating variant (PTV)-intolerant (PI) genes 2) genes expressed in brain cell types and neurons ascertained from mouse and human brain tissue 3) genes defined by synaptic function and location and 4) intersection genes, i.e., PI genes that are expressed in the human and mouse brain cell gene-sets. We show that common as well as ultra-rare schizophrenia-associated variants are overrepresented in PI genes, in excitatory neurons from the prefrontal cortex and hippoc us, medium spiny neurons, and genes enriched for synaptic processes. We also observed stronger enrichment in the intersection genes. Our findings suggest that across the allele frequency spectrum, genes and genetic variants likely to be under stringent selection, and those expressed in particular brain cell types, are involved in the same biological pathways influencing the risk for schizophrenia.
Heritability and genomics of gene expression in peripheral blood
Publisher: Springer Science and Business Media LLC
Date: 13-04-2014
DOI: 10.1038/NG.2951
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Publisher: Springer Science and Business Media LLC
Date: 11-08-2202
DOI: 10.1038/NG.2711
Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism, Anxiety and Depression
Publisher: Springer Science and Business Media LLC
Date: 10-01-2007
DOI: 10.1007/S10519-006-9139-7
Abstract: We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P<0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression.
Prevalence of mental illness among parents of children receiving treatment within child and adolescent mental health services (CAMHS): a scoping review
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies
Publisher: Elsevier BV
Date: 09-2020
Genetic association study of childhood aggression across raters, instruments, and age
Publisher: Springer Science and Business Media LLC
Date: 30-07-2021
DOI: 10.1038/S41398-021-01480-X
Abstract: Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for s le overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG overall ) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG overall . The gene-based analysis returned three significant genes: ST3GAL3 ( P = 1.6E–06), PCDH7 ( P = 2.0E–06), and IPO13 ( P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout s le of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations ( r g ) among rater-specific assessment of AGG ranged from r g = 0.46 between self- and teacher-assessment to r g = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r g s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation ( r g = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes
Publisher: Springer Science and Business Media LLC
Date: 04-04-2012
DOI: 10.1038/EJHG.2012.47
Gene-environment interaction in teacher-rated internalizing and externalizing problem behavior in 7- to 12-year-old twins
Publisher: Wiley
Date: 23-04-2012
DOI: 10.1111/J.1469-7610.2011.02497.X
Abstract: Internalizing and externalizing problem behavior at school can have major consequences for a child and is predictive for disorders later in life. Teacher ratings are important to assess internalizing and externalizing problems at school. Genetic epidemiological studies on teacher-rated problem behavior are relatively scarce and the reported heritability estimates differ widely. A unique feature of teacher ratings of twins is that some pairs are rated by different and others are rated by the same teacher. This offers the opportunity to assess gene-environment interaction. Teacher ratings of 3,502 7-year-old, 3,134 10-year-old and 2,193 12-year-old twin pairs were analyzed with structural equation modeling. About 60% of the twin pairs were rated by the same teacher. Twin correlations and the heritability of internalizing and externalizing behavior were estimated, separately for pairs rated by the same and different teachers. Socioeconomic status and externalizing behavior at age 3 were included as covariates. Twin correlations and heritability estimates were higher when twin pairs were in the same class and rated by the same teacher than when pairs were rated by different teachers. These differences could not be explained by twin confusion or rater bias. When twins were rated by the same teacher, heritability estimates were about 70% for internalizing problems and around 80% in boys and 70% in girls for externalizing problems. When twins were rated by different teachers, heritability estimates for internalizing problems were around 30% and for externalizing problems around 50%. Exposure to different teachers during childhood may affect the heritability of internalizing and externalizing behavior at school. This finding points to gene-environment interaction and is important for the understanding of childhood problem behavior. In addition, it could imply an opportunity for interventions at school.
The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls
Publisher: Elsevier BV
Date: 07-2020
A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms
Publisher: Springer Science and Business Media LLC
Date: 18-01-2019
DOI: 10.1007/S10519-018-09947-2
Abstract: We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 in iduals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753 p-value = 3.02 × 10
Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
Publisher: Oxford University Press (OUP)
Date: 24-11-2015
DOI: 10.1093/HMG/DDV472
Behavior genetics: From heritability to gene finding
Publisher: Cambridge University Press
Date: 2016
Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults
Publisher: American Medical Association (AMA)
Date: 04-2019
DOI: 10.1001/JAMAPSYCHIATRY.2018.4175
Abstract: Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear physical activity may protect against depression, and/or depression may result in decreased physical activity. To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference. This 2-s le mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes—self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)—and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in erse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR–Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018. MDD and physical activity. GWAS summary data were available for a combined s le size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in mean acceleration 95% CI, 0.59-0.92 P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = −0.08 in mean acceleration per MDD vs control status 95% CI, −0.47 to 0.32 P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity 95% CI, 0.57-3.37 P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status 95% CI, −0.008 to 0.05 P = .15). Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed—but not self-reported—physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.
Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder
Publisher: Springer Science and Business Media LLC
Date: 15-03-2019
DOI: 10.1038/S41398-019-0451-4
Abstract: The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics, and genetically predicted expression levels in different tissues, using the online tool Drug Targetor ( drugtargetor.com ). We also investigated drug-target relationships that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 153 protein-coding genes are significantly associated with MDD in MAGMA after multiple testing correction among these, five are predicted to be down or upregulated in brain regions and 24 are known druggable genes. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics, and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings not only require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new—and better—treatment options.
Parental characteristics and offspring mental health and related outcomes: a systematic review of genetically informative literature
Publisher: Springer Science and Business Media LLC
Date: 04-2021
DOI: 10.1038/S41398-021-01300-2
Abstract: Various parental characteristics, including psychiatric disorders and parenting behaviours, are associated with offspring mental health and related outcomes in observational studies. The application of genetically informative designs is crucial to disentangle the role of genetic and environmental factors (as well as gene–environment correlation) underlying these observations, as parents provide not only the rearing environment but also transmit 50% of their genes to their offspring. This article first provides an overview of behavioural genetics, matched-pair, and molecular genetics designs that can be applied to investigate parent–offspring associations, whilst modelling or accounting for genetic effects. We then present a systematic literature review of genetically informative studies investigating associations between parental characteristics and offspring mental health and related outcomes, published since 2014. The reviewed studies provide reliable evidence of genetic transmission of depression, criminal behaviour, educational attainment, and substance use. These results highlight that studies that do not use genetically informative designs are likely to misinterpret the mechanisms underlying these parent–offspring associations. After accounting for genetic effects, several parental characteristics, including parental psychiatric traits and parenting behaviours, were associated with offspring internalising problems, externalising problems, educational attainment, substance use, and personality through environmental pathways. Overall, genetically informative designs to study intergenerational transmission prove valuable for the understanding of in idual differences in offspring mental health and related outcomes, and mechanisms of transmission within families.
Life events and borderline personality features: the influence of gene–environment interaction and gene–environment correlation
Publisher: Cambridge University Press (CUP)
Date: 07-2010
DOI: 10.1017/S0033291710001297
Abstract: Traumatic life events are generally more common in patients with borderline personality disorder (BPD) than in non-patients or patients with other personality disorders. This study investigates whether exposure to life events moderates the genetic architecture of BPD features. As the presence of genotype–environment correlation ( r GE ) can lead to spurious findings of genotype–environment interaction (G×E), we also test whether BPD features increase the likelihood of exposure to life events. The extent to which an in idual is at risk to develop BPD was assessed with the Personality Assessment Inventory – Borderline features scale (PAI-BOR). Life events under study were a orce/break-up, traffic accident, violent assault, sexual assault, robbery and job loss. Data were available for 5083 twins and 1285 non-twin siblings. Gene–environment interaction and correlation were assessed by using structural equation modelling (SEM) and the co-twin control design. There was evidence for both gene–environment interaction and correlation. Additive genetic influences on BPD features interacted with the exposure to sexual assault, with genetic variance being lower in exposed in iduals. In in iduals who had experienced a orce/break-up, violent assault, sexual assault or job loss, environmental variance for BPD features was higher, leading to a lower heritability of BPD features in exposed in iduals. Gene–environment correlation was present for some life events. The genes that influence BPD features thus also increased the likelihood of being exposed to certain life events. To our knowledge, this study is the first to test the joint effect of genetic and environmental influences and the exposure to life events on BPD features in the general population. Our results indicate the importance of both genetic vulnerability and life events.
A prospective study of the effects of breastfeeding and FADS2 polymorphisms on cognition and hyperactivity/attention problems
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1002/AJMG.B.32175
Abstract: Breastfeeding has been associated with improved cognitive functioning. There is a beneficial effect on IQ, and possibly on associated phenotypes such as attention problems. It has been suggested that the effect on IQ is moderated by polymorphisms in the FADS2 gene, which is involved in fatty acid metabolism. In this study we tested the relation between breastfeeding and FADS2 polymorphisms on the one hand and IQ, educational attainment, overactivity, and attention problems on the other hand. IQ at age 5, 7, 10, 12, and/or 18 (n = 1,313), educational attainment at age 12 (n = 1,857), overactive behavior at age 3 (n = 2,560), and attention problems assessed at age 7, 10, and 12 years (n = 2,479, n = 2,423, n = 2,226) were predicted by breastfeeding and two SNPs in FADS2 (rs174575 and rs1535). Analyses were performed using structural equation modeling. After correction for maternal education, a main effect of breastfeeding was found for educational attainment at age 12 and overactive behavior at age 3. For IQ, the effect of breastfeeding across age was marginally significant (P = 0.05) and amounted to 1.6 points after correcting for maternal education. Neither a main effect of the FADS2 polymorphisms nor an interaction with breastfeeding was detected for any of the phenotypes. This developmentally informed study confirms that breastfeeding is associated with higher educational attainment at age 12, less overactive behavior at age 3 and a trend toward higher IQ after correction for maternal education. In general, the benefits of breastfeeding were small and did not interact with SNPs in FADS2.
Genetic and Environmental Stability of Neuroticism From Adolescence to Adulthood
Publisher: Cambridge University Press (CUP)
Date: 20-11-2015
DOI: 10.1017/THG.2015.80
Abstract: Longitudinal studies of neuroticism have shown that, on average, neuroticism scores decrease from adolescence to adulthood. The heritability of neuroticism is estimated between 0.30 and 0.60 and does not seem to vary greatly as a function of age. Shared environmental effects are rarely reported. Less is known about the role of genetic and environmental influences on the rank order stability of neuroticism in the period from adolescence to adulthood. We studied the stability of neuroticism in a cohort sequential (classical) twin design, from adolescence (age 14 years) to young adulthood (age 32 years). A genetic simplex model that was fitted to the longitudinal neuroticism data showed that the genetic stability of neuroticism was relatively high (genetic correlations between adjacent age bins .9), and increased from adolescence to adulthood. Environmental stability was appreciably lower (environmental correlations between adjacent age bins were between 0.3 and 0.6). This low stability was largely due to age-specific environmental variance, which was dominated by measurement error. This attenuated the age-to-age environmental correlations. We constructed an environmental covariance matrix corrected for this error, under the strong assumption that all age-specific environmental variance is error variance. The environmental (co)variance matrix corrected for attenuation revealed highly stable environmental influences on neuroticism (correlations between adjacent age bins were between 0.7 and 0.9). Our results indicate that both genetic and environmental influences have enduring effects on in idual differences in neuroticism.
Meta-analysis of genome-wide association studies of anxiety disorders
Publisher: Springer Science and Business Media LLC
Date: 12-01-2016
DOI: 10.1038/MP.2015.197
A genome-wide approach to children's aggressive behavior:The EAGLE consortium
Publisher: Wiley
Date: 18-06-2015
DOI: 10.1002/AJMG.B.32333
Abstract: In idual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest s le exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed s le and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total s le. GCTA quantified variance tagged by common SNPs (10-54%). The meta-analysis of the total s le identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P = 5.30 × 10(-8) ). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc.
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Publisher: Springer Science and Business Media LLC
Date: 11-06-2019
DOI: 10.1038/S41467-019-10461-0
Abstract: Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
Synaptic and brain-expressed gene sets relate to the shared genetic risk across five psychiatric disorders
Publisher: Cambridge University Press (CUP)
Date: 22-07-2019
DOI: 10.1017/S0033291719001776
Abstract: Mounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders. We applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls. We identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex. We obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to in idual disorders play a role in a broader range of psychiatric disorders.
Unraveling the genetic architecture of major depressive disorder: merits and pitfalls of the approaches used in genome-wide association studies
Publisher: Cambridge University Press (CUP)
Date: 27-09-2019
DOI: 10.1017/S0033291719002502
Abstract: To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize s le size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing s le size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, s les containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.
Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder
Publisher: Public Library of Science (PLoS)
Date: 20-12-2018
One mental health problem influencing the risk for another, within individuals and between siblings. Commentary on Allegrini et al. (2022)
Publisher: Wiley
Date: 24-08-2022
DOI: 10.1002/JCV2.12102
Practitioner Review: It's time to bridge the gap – understanding the unmet needs of consumers with attention‐deficit/hyperactivity disorder – a systematic review and recommendations
Publisher: Wiley
Date: 18-01-2023
DOI: 10.1111/JCPP.13752
Abstract: Understanding the unmet needs of healthcare consumers with attention‐deficit/hyperactivity disorder (ADHD) (in iduals with ADHD and their caregivers) provides critical insight into gaps in services, education and research that require focus and funding to improve outcomes. This review examines the unmet needs of ADHD consumers from a consumer perspective. A standardised search protocol identified peer‐reviewed studies published between December 2011 and December 2021 focusing on consumer‐identified needs relating to ADHD clinical care or research priorities. 1,624 articles were screened with 23 studies that reviewed examining the needs of ADHD consumers from Europe, the U.K., Hong Kong, Iran, Australia, the U.S.A. and Canada. Consumer‐identified needs related to: treatment that goes beyond medication (12 studies) improved ADHD‐related education/training (17 studies) improved access to clinical services, carer support and financial assistance (14 studies) school accommodations/support (6 studies) and ongoing treatment efficacy research (1 study). ADHD consumers have substantial unmet needs in clinical, psychosocial and research contexts. Recommendations to address these needs include: improving access to and quality of multimodal care provision incorporating recovery principles into care provision fostering ADHD health literacy and increasing consumer participation in research, service development and ADHD‐related training/education.
A simplified method to estimate the soil-water characteristic curve
Publisher: Canadian Science Publishing
Date: 12-2010
DOI: 10.1139/T10-033
Abstract: This paper proposes a simplified method to estimate the soil-water characteristic curve (SWCC) for both coarse- and fine-grained soils using one-point SWCC measurement and basic index properties. Parameters of the Fredlund and Xing SWCC equation were correlated with the basic properties of 60 soils: 30 soils each of coarse- and fine-grained types. Sensitivity analysis revealed that the location of the one-point measurement at matric suctions of 10 and 500 kPa gave the most reliable SWCC using the proposed method for coarse- and fine-grained soils, respectively. The validity of the proposed method was evaluated using a total of 62 soils collated from published literature with 31 soils each of the coarse- and fine-grained types. The proposed method gives a good estimation of the SWCC and uses fewer parameters when compared with existing one-point SWCC estimation methods.
Differential DNA Methylation is associated with Hippocampal Abnormalities in Pediatric Posttraumatic Stress Disorder
Publisher: Research Square Platform LLC
Date: 23-10-2020
DOI: 10.21203/RS.3.RS-87419/V1
Abstract: Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. Therefore, we combine genome-wide epigenetic and structural neuroimaging measures in a Dutch cohort of youth with PTSD (ages 8-18 years). We aimed to replicate findings in a similar independent American cohort. We found significant methylome-wide associations for pediatric PTSD (FDR p .05) compared to non-PTSD control groups (traumatized and non-traumatized youth). Methylation differences on 9 genes were replicated, including genes related to glucocorticoid functioning. In both cohorts, methylation on OLFM3 gene was further associated with anterior hippoc al volume. These findings point to molecular pathways involved in inflammation, stress response, and neuroplasticity as potential contributors to neural abnormalities and provide potentially unique biomarkers and treatment targets for pediatric PTSD.
Attention-deficit/hyperactivity disorder polygenic risk scores predict attention problems in a population-based sample of children
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JAAC.2014.06.014
Abstract: Clinically, attention-deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impulsivity, and inattention and is among the most common childhood disorders. These same traits that define ADHD are variable in the general population, and the clinical diagnosis may represent the extreme end of a continuous distribution of inattentive and hyperactive behaviors. This hypothesis can be tested by assessing the predictive value of polygenic risk scores derived from a discovery s le of ADHD patients in a target s le from the general population with continuous scores of inattention and hyperactivity. In addition, the genetic overlap between ADHD and continuous ADHD scores can be tested across rater and age. The Psychiatric Genomics Consortium has performed the largest genome-wide analysis (GWA) study of ADHD so far, including 5,621 clinical patients and 13,589 controls. The effects sizes of single nucleotide polymorphisms (SNPs) estimated in this meta-analysis were used to obtain in idual polygenic risk scores in an independent population-based cohort of 2,437 children from the Netherlands Twin Register. The variance explained in Attention Problems (AP) scale scores by the polygenic risk scores was estimated by linear mixed modeling. The ADHD polygenic risk scores significantly predicted both parent and teacher ratings of AP in preschool- and school-aged children. These results indicate genetic overlap between a diagnosis of ADHD and AP scale scores across raters and age groups and provides evidence for a dimensional model of ADHD. Future GWA studies on ADHD can likely benefit from the inclusion of population-based cohorts and the analysis of continuous scores.
The impact of environmental experiences on symptoms of anxiety and depression across the life span
Publisher: SAGE Publications
Date: 23-09-2011
Abstract: Symptoms of anxiety and depression are relatively stable over time. Can this stability be explained by genetic influences, or is it caused by the long-lasting effects of accumulating environmental experiences? To address this question, we analyzed longitudinally assessed symptoms of anxiety and depression in eight s les of monozygotic twins of widely varying ages. These s les were drawn from American and European population-based registries. Using hierarchical linear modeling, we examined in idual differences and in idual changes in the level of symptoms over time. This method enabled us to decompose the variance into the predictable variance shared by both members of each pair of twins, the differences between in iduals within pairs, and the residual variance. We then modeled how these components of in idual variation changed over time. Within pairs, the twins’ predicted levels of symptoms increasingly erged from childhood until late adulthood, at which point the ergence ceased. By middle adulthood, environmental experiences contributed substantially to stable and predictable interin idual differences in levels of anxiety and depression.
Genetic Overlap Between Schizophrenia and Developmental Psychopathology: Longitudinal and Multivariate Polygenic Risk Prediction of Common Psychiatric Traits During Development
Publisher: Oxford University Press (OUP)
Date: 11-03-2017
Ultra-rare and common genetic variant analysis converge to implicate negative selection and neuronal processes in the aetiology of schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 03-06-2022
DOI: 10.1038/S41380-022-01621-8
Abstract: Both common and rare genetic variants (minor allele frequency % and .1% respectively) have been implicated in the aetiology of schizophrenia. In this study, we integrate single-cell gene expression data with publicly available Genome-Wide Association Study (GWAS) and exome sequenced data in order to investigate in parallel, the enrichment of common and (ultra-)rare variants related to schizophrenia in several functionally relevant gene-sets. Four types of gene-sets were constructed 1) protein-truncating variant (PTV)-intolerant (PI) genes 2) genes expressed in brain cell types and neurons ascertained from mouse and human brain tissue 3) genes defined by synaptic function and location and 4) intersection genes, i.e., PI genes that are expressed in the human and mouse brain cell gene-sets. We show that common as well as ultra-rare schizophrenia-associated variants are overrepresented in PI genes, in excitatory neurons from the prefrontal cortex and hippoc us, medium spiny neurons, and genes enriched for synaptic processes. We also observed stronger enrichment in the intersection genes. Our findings suggest that across the allele frequency spectrum, genes and genetic variants likely to be under stringent selection, and those expressed in particular brain cell types, are involved in the same biological pathways influencing the risk for schizophrenia.
Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty
Publisher: Oxford University Press (OUP)
Date: 25-04-2014
DOI: 10.1093/HMG/DDU150
Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
Publisher: Springer Science and Business Media LLC
Date: 08-10-2018
DOI: 10.1038/S42003-018-0155-Y
Abstract: Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree ( n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected in iduals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned
Publisher: Springer Science and Business Media LLC
Date: 02-11-2010
DOI: 10.1038/MP.2010.109
Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia
Publisher: SAGE Publications
Date: 17-12-2020
Abstract: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). Parents of 213 Australian children (5–17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4 95% CI 0.3–0.6), less outdoor time (OR = 0.4 95% 0.3–0.6), and less enjoyment in activities (OR = 6.5 95% CI 4.0–10.4), while television (OR = 4.0 95% CI 2.5–6.5), social media (OR = 2.4 95% CI 1.3–4.5), gaming (OR = 2.0 95% CI 1.3–3.0), sad/depressed mood (OR = 1.8 95% CI 1.2–2.8), and loneliness (OR = 3.6 95% CI 2.3–5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.
Analysis of shared heritability in common disorders of the brain
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-06-2018
Abstract: Consistent classification of neuropsychiatric diseases is problematic because it can lead to misunderstanding of etiology. The Brainstorm Consortium examined multiple genome-wide association studies drawn from more than 200,000 patients for 25 brain-associated disorders and 17 phenotypes. Broadly, it appears that psychiatric and neurologic disorders share relatively little common genetic risk. However, different and independent pathways can result in similar clinical manifestations (e.g., psychosis, which occurs in both schizophrenia and Alzheimer's disease). Schizophrenia correlated with many psychiatric disorders, whereas the immunopathological affliction Crohn's disease did not, and posttraumatic stress syndrome was also largely independent of underlying traits. Essentially, the earlier the onset of a disorder, the more inheritable it appeared to be. Science , this issue p. eaap8757
Crying without a cause and being easily upset in two-year-olds: Heritability and predictive power of behavioral problems
Publisher: Cambridge University Press (CUP)
Date: 10-2011
Abstract: In order to estimate the influence of genetic and environmental factors on ‘crying without a cause’ and ‘being easily upset’ in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset ( r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28–.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems.
Examining the pharmacological and psychological treatment of child and adolescent ADHD in Australia: Protocol for a retrospective cohort study using linked national registry data
Publisher: BMJ
Date: 11-2022
DOI: 10.1136/BMJOPEN-2022-064920
Abstract: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder which affects 5% of children globally. In Australia, it is estimated that 4.1% of children and adolescents have ADHD. While research has examined the treatment and outcomes of children with ADHD attending public mental health services during their time in the public system in Australia, it is not known what treatment they received before and after these treatment episodes, which will provide a more complete understanding of these children’s treatment journey. We will link clinical data from cohorts of children and adolescents treated in the public child and youth mental health and/or child development services in Brisbane, Melbourne and Sydney to the Medicare Benefits Schedule (MBS), Pharmaceutical Benefits Scheme (PBS) and National Death Index. MBS data will demonstrate the treatment journey with respect to clinicians seen, and treatment episodes from the public health service data sets will be examined to assess if the type and intensity of treatment are related to treatment outcomes. PBS data will reveal all psychotropic medications prescribed, allowing an examination of not just ADHD medications, but also other psychotropics which may indicate co-occurring conditions (eg, anxiety and mood disorders). Statistical analyses will include descriptive statistics to describe the rates of specific medications and clinician specialties seen. Linear and logistic regression will be used to model how treatment and sociodemographic variables relate to routinely collected outcome measures in the public health system while controlling for covarying factors. This study has been approved by the following institutional ethics committees: (1) Children’s Health Queensland Hospital and Health Service (HREC/21/QCHQ/76260), (2) The University of Queensland (2021/HE002143) and (3) The Australian Institute of Health and Welfare (EO2021/4/1300). Findings will be disseminated through peer-reviewed journals, conferences, professional associations and to public mental health services that treat ADHD.
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
Publisher: Oxford University Press (OUP)
Date: 27-02-2013
DOI: 10.1093/HMG/DDT104
Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3–16 years from multiple raters in six cohorts in the EU-ACTION project
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts
Publisher: Elsevier BV
Date: 10-2016
Collaborative meta-Analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
Publisher: Springer Science and Business Media LLC
Date: 04-04-2018
DOI: 10.1038/MP.2017.44
Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology
Publisher: Wiley
Date: 24-10-2017
DOI: 10.1002/AJMG.B.32500
Joint developmental trajectories of internalizing and externalizing disorders between childhood and adolescence
Publisher: Cambridge University Press (CUP)
Date: 18-07-2016
DOI: 10.1017/S0954579416000572
Abstract: This study sought to identify trajectories of DSM-IV based internalizing (INT) and externalizing (EXT) problem scores across childhood and adolescence and to provide insight into the comorbidity by modeling the co-occurrence of INT and EXT trajectories. INT and EXT were measured repeatedly between age 7 and age 15 years in over 7,000 children and analyzed using growth mixture models. Five trajectories were identified for both INT and EXT, including very low, low, decreasing, and increasing trajectories. In addition, an adolescent onset trajectory was identified for INT and a stable high trajectory was identified for EXT. Multinomial regression showed that similar EXT and INT trajectories were associated. However, the adolescent onset INT trajectory was independent of high EXT trajectories, and persisting EXT was mainly associated with decreasing INT. Sex and early life environmental risk factors predicted EXT and, to a lesser extent, INT trajectories. The association between trajectories indicates the need to consider comorbidity when a child presents with INT or EXT disorders, particularly when symptoms start early. This is less necessary when INT symptoms start at adolescence. Future studies should investigate the etiology of co-occurring INT and EXT and the specific treatment needs of these severely affected children.
Related Organisations
Children's Health Queensland Hospital And Health Service
Location: Australia
Related Funding Activities
Discovery Projects - Grant ID: DP200102159
Start Date: 03-2020
End Date: 04-2023
Amount: $560,468.00
Funder: Australian Research Council
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