@article {455, title = {Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms}, journal = {Journal of the American Academy of Child \& Adolescent Psychiatry}, volume = {61}, year = {2022}, pages = {934{\textendash}945}, abstract = {

OBJECTIVE: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence.

METHOD: 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 sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.

RESULTS: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66\%, 95\% CI = 0.84-2.48

}, keywords = {anxiety, Depression, genetic epidemiology, molecular genetics, repeated measures}, doi = {10.1016/j.jaac.2021.11.035}, author = {Jami, Eshim S and Hammerschlag, Anke R and Ip, Hill F and Allegrini, Andrea G and Benyamin, Beben and Border, Richard and Diemer, Elizabeth W and Jiang, Chang and Karhunen, Ville and Lu, Yi and Lu, Qing and Mallard, Travis T and Mishra, Pashupati P and Nolte, Ilja M and Palviainen, Teemu and Peterson, Roseann E and Sallis, Hannah M and Shabalin, Andrey A and Tate, Ashley E and Thiering, Elisabeth and Vilor-Tejedor, Nat{\`a}lia and Wang, Carol and Zhou, Ang and Adkins, Daniel E and Alemany, Silvia and Ask, Helga and Chen, Qi and Corley, Robin P and Ehli, Erik A and Evans, Luke M and Havdahl, Alexandra and Hagenbeek, Fiona A and Hakulinen, Christian and Henders, Anjali K and Hottenga, Jouke Jan and Korhonen, Tellervo and Mamun, Abdullah and Marrington, Shelby and Neumann, Alexander and Rimfeld, Kaili and Rivadeneira, Fernando and Silberg, Judy L and van Beijsterveldt, Catharina E and Vuoksimaa, Eero and Whipp, Alyce M and Tong, Xiaoran and Andreassen, Ole A and Boomsma, Dorret I and Brown, Sandra A and Burt, S Alexandra and Copeland, William and Dick, Danielle M and Harden, K Paige and Harris, Kathleen Mullan and Hartman, Catharina A and Heinrich, Joachim and Hewitt, John K and Hopfer, Christian and Hypponen, Elina and Jarvelin, Marjo-Riitta and Kaprio, Jaakko and Keltikangas-J{\"a}rvinen, Liisa and Klump, Kelly L and Krauter, Kenneth and Kuja-Halkola, Ralf and Larsson, Henrik and Lehtim{\"a}ki, Terho and Lichtenstein, Paul and Lundstr{\"o}m, Sebastian and Maes, Hermine H and Magnus, Per and Munaf{\`o}, Marcus R and Najman, Jake M and Nj{\o}lstad, P\aal R and Oldehinkel, Albertine J and Pennell, Craig E and Plomin, Robert and Reichborn-Kjennerud, Ted and Reynolds, Chandra and Rose, Richard J and Smolen, Andrew and Snieder, Harold and Stallings, Michael and Standl, Marie and Sunyer, Jordi and Tiemeier, Henning and Wadsworth, Sally J and Wall, Tamara L and Whitehouse, Andrew J O and Williams, Gail M and Ystr{\o}m, Eivind and Nivard, Michel G and Bartels, Meike and Middeldorp, Christel M} } @article {465, title = {Overview of CAPICE - Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe - an EU Marie Sk{\l}odowska-Curie International Training Network}, journal = {European Child \& Adolescent Psychiatry}, volume = {31}, year = {2022}, pages = {829{\textendash}839}, 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 individual 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).

}, keywords = {anxiety, Attention deficit hyperactivity disorder (ADHD), Childhood and adolescence psychopathology, Depression, Psychiatric genetics}, doi = {10.1007/s00787-020-01713-2}, author = {Rajula, Hema Sekhar Reddy and Manchia, Mirko and Agarwal, Kratika and Akingbuwa, Wonuola A and Allegrini, Andrea G and Diemer, Elizabeth and Doering, Sabrina and Haan, Elis and Jami, Eshim S and Karhunen, Ville and Leone, Marica and Schellhas, Laura and Thompson, Ashley and van den Berg, St{\'e}phanie M and Bergen, Sarah E and Kuja-Halkola, Ralf and Hammerschlag, Anke R and J{\"a}rvelin, Marjo Riitta and Leval, Amy and Lichtenstein, Paul and Lundstr{\"o}m, Sebastian and Mauri, Matteo and Munaf{\`o}, Marcus R and Myers, David and Plomin, Robert and Rimfeld, Kaili and Tiemeier, Henning and Ystrom, Eivind and Fanos, Vassilios and Bartels, Meike and Middeldorp, Christel M} } @article {407, title = {Anxiety at age 15 predicts psychiatric diagnoses and suicidal ideation in late adolescence and young adulthood: results from two longitudinal studies}, journal = {BMC Psychiatry}, volume = {19}, year = {2019}, pages = {363}, abstract = {

BACKGROUND: 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/psychotic-, 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.

METHODS: 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 sample 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.

RESULTS: 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.

CONCLUSION: 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.

}, keywords = {Adolescence, Anxiety disorders, Depressive disorders, Neurodevelopmental disorders, Suicidal ideation, Young adulthood}, doi = {10.1186/s12888-019-2349-3}, author = {Doering, Sabrina and Lichtenstein, Paul and Gillberg, Christopher and NTR and Middeldorp, Christel M and Bartels, Meike and Kuja-Halkola, Ralf and Lundstr{\"o}m, Sebastian} } @article {416, title = {The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects}, journal = {European Journal of Epidemiology}, volume = {34}, year = {2019}, pages = {279{\textendash}300}, abstract = {

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.

}, keywords = {Childhood traits and disorders, Consortium, genetics, longitudinal}, doi = {10.1007/s10654-019-00502-9}, author = {Middeldorp, Christel M and Felix, Janine F and Mahajan, Anubha and EArly Genetics Lifecourse Epidemiology (EAGLE) consortium and Early Growth Genetics (EGG) consortium and McCarthy, Mark I} } @article {406, title = {Do parental psychiatric symptoms predict outcome in children with psychiatric disorders? A naturalistic clinical study}, journal = {Journal of the American Academy of Child \& Adolescent Psychiatry}, volume = {57}, year = {2018}, pages = {669{\textendash}677.e6}, abstract = {

OBJECTIVE: Parental psychiatric symptoms can negatively affect the outcome of children\&$\#$39;s psychopathology. Studies thus far have mainly shown a negative effect of maternal depression. This study examined the associations between a broad range of psychiatric symptoms in mothers and fathers and the child\&$\#$39;s outcome.

METHOD: 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\&$\#$39;s symptoms scores were tested at follow-up by parental symptom scores at baseline, parental scores at follow-up, and offspring scores at baseline.

RESULTS: 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.

CONCLUSION: 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.

}, keywords = {child psychopathology, longitudinal, Parent-offspring associations, Parental psychopathology}, doi = {10.1016/j.jaac.2018.05.017}, author = {Wesseldijk, Laura W and Dieleman, Gwen C and van Steensel, Francisca J A and Bleijenberg, Ellen J and Bartels, Meike and B{\"o}gels, Susan M and Middeldorp, Christel M} } @article {402, title = {Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology}, journal = {American Journal of Medical Genetics Part B: Neuropsychiatric Genetics}, volume = {174}, year = {2017}, pages = {251{\textendash}260}, abstract = {

The assessment of children\&$\#$39;s psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child\&$\#$39;s problems (r 0.60-0.75). The heritability was estimated over 55\% for maternal and paternal ratings for all scales, except for conduct problems (44-46\%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13\%), oppositional (13\%), and conduct problems (37\%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child\&$\#$39;s psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. \copyright{} 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

}, keywords = {parental ratings, psychopathology, rater bias, shared environment, twins}, doi = {10.1002/ajmg.b.32500}, author = {Wesseldijk, Laura W and Fedko, Iryna O and Bartels, Meike and Nivard, Michel G and van Beijsterveldt, Catharina E M and Boomsma, Dorret I and Middeldorp, Christel M} }